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Ehret F, El Baya L, Erridge SC, Bussière M, Verhoeff JJC, Niyazi M, Preusser M, Minniti G, Shih HA. Radiation Therapy for Meningiomas - Where Do We Stand and What's on the Horizon? Int J Radiat Oncol Biol Phys 2025; 121:599-612. [PMID: 39476990 DOI: 10.1016/j.ijrobp.2024.10.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 09/15/2024] [Accepted: 10/13/2024] [Indexed: 12/22/2024]
Abstract
Radiation therapy, including conventionally fractionated external beam radiation therapy, stereotactic radiosurgery, and fractionated stereotactic radiation therapy, is a cornerstone in the interdisciplinary management of meningiomas. Recent advances in radiation oncology and also in other fields, such as neuropathology and imaging, have various implications for meningioma radiation therapy. This review aims to summarize current and anticipated developments, as well as active clinical trials related to the use of radiation therapy for meningiomas. In imaging, positron emission tomography has proven valuable for assessing the spatial extension of meningiomas and may enhance target delineation, treatment response monitoring, and recurrence assessment after radiation therapy. Particle therapy, including protons and carbon ions, as well as stereotactic radiosurgery and fractionated stereotactic radiation therapy, allow for conformal treatments that permit dose escalation in selected patients with high-grade meningiomas. Additionally, emerging integrated molecular and genetic classifications offer superior risk stratification and may refine patient selection for radiation therapy. However, there is a paucity of active meningioma trials directly investigating or refining the use of radiation therapy. In summary, significant advances in functional imaging, molecular and genetic diagnostics, and radiation treatment techniques hold the potential to improve patient outcomes and to avoid over- and undertreatment. Collaborative efforts and further clinical trials are essential to optimize meningioma radiation therapy.
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Affiliation(s)
- Felix Ehret
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, USA; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Radiation Oncology, Berlin, Germany; German Cancer Consortium (DKTK), partner site Berlin, a partnership between DKFZ and Charité - Universitätsmedizin Berlin, Germany.
| | - Leon El Baya
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, USA
| | - Sara C Erridge
- Edinburgh Centre for Neuro-Oncology, University of Edinburgh, Edinburgh, Scotland
| | - Marc Bussière
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, USA
| | - Joost J C Verhoeff
- Department of Radiation Oncology, Amsterdam UMC, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Maximilian Niyazi
- Department of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany
| | - Matthias Preusser
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Giuseppe Minniti
- Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome; IRCCS Neuromed, Pozzilli (IS), Italy
| | - Helen A Shih
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, USA
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Hadji-Turdeghal K, Fosbøl MØ, Hasbak P, Löfgren J, Bull Rasmussen I, Bundgaard H, Iversen K, Bruun NE, Møller CH, Tuxen C, Johannesen HH, Køber L, Kjær A, Ripa RS, Fosbøl EL. First-In-Human Study of [ 64Cu]Cu-DOTATATE PET/CT in Infective Endocarditis: A Prospective Head-to-Head Comparison With [ 18F]FDG. Circ Cardiovasc Imaging 2025; 18:e017156. [PMID: 39902600 DOI: 10.1161/circimaging.124.017156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 11/15/2024] [Indexed: 02/05/2025]
Abstract
BACKGROUND Infective endocarditis (IE) can be challenging to diagnose. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[18F]-fluoro-d-glucose ([18F]FDG) is recommended as a diagnostic tool in the guidelines, but holds limitations. The aim of this study was to compare the tracer uptake between the novel [64Cu]Cu-DOTATATE, which has low cardiac uptake and does not require fasting or dietary restrictions, and [18F]FDG in patients with IE and examine the sensitivity and specificity. METHODS The CuDOS study (Cu-Dotatate Positron Emissions Tomography in Infective Endocarditis) was a prospective study including 20 patients with IE (10 with prosthetic valve endocarditis and 10 with native valve endocarditis) and 20 controls. All participants underwent [64Cu]Cu-DOTATATE and [18F]FDG PET/CT. Scans were read blinded to clinical data. Tracer uptakes were measured as maximum standardized uptake values in each heart valve. Differences were tested with Wilcoxon rank tests. RESULTS The median age of the cases and controls was 68 years (interquartile range [IQR], 55.0-75.5) and 61 years (IQR, 57.0-69.5), respectively. [64Cu]Cu-DOTATATE uptake (median maximum standardized uptake value [IQR]) in patients with IE was higher than in controls (2.34 [1.40-3.23] versus 1.44 [1.21-1.60]; P =0.008), although this difference was mainly driven by prosthetic valve endocarditis cases (3.23 [2.02-3.86]; P <0.001) and not between native valve endocarditis cases and controls (1.51 [1.23-2.58]; P=0.428). The sensitivity of [64Cu]Cu-DOTATATE and [18F]FDG PET/CT in 20 cases versus 20 controls were equal, and the specificity was 90% and 75%, respectively. The analysis of prosthetic valve endocarditis versus the 20 controls showed equal sensitivity (80%), and a specificity of 90% and 75%, respectively (P =0.38). In addition, a greater proportion of scans achieved diagnostic certainty with [64Cu]Cu-DOTATATE PET/CT compared with [18F]FDG PET/CT for native valve endocarditis, prosthetic valve endocarditis, and controls. CONCLUSIONS [64Cu]Cu-DOTATATE PET/CT showed uptake in the infected valve in patients with IE, and has major advantage as it does not require any preparation compared with [18F]FDG. [64Cu]Cu-DOTATATE had a numerically higher specificity than [18F]FDG, although the difference was not statistically significant. Both tracers were limited in the detection of native valve endocarditis. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT05432427. www.clinicaltrialsregister.eu; Unique identifier: 2021-005501-27.
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Affiliation(s)
- Katra Hadji-Turdeghal
- Department of Cardiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen (K.H.-T., H.B., L.K., E.L.F.)
| | - Marie Øbro Fosbøl
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen (M.O.F., P.H., J.L., H.H.J., A.K.ær, R.S.R.)
- Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet & Department of Biomedical Sciences (M.O.F., A.K.ær, R.S.R.), University of Copenhagen, Copenhagen, Denmark
| | - Philip Hasbak
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen (M.O.F., P.H., J.L., H.H.J., A.K.ær, R.S.R.)
| | - Johan Löfgren
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen (M.O.F., P.H., J.L., H.H.J., A.K.ær, R.S.R.)
| | | | - Henning Bundgaard
- Department of Cardiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen (K.H.-T., H.B., L.K., E.L.F.)
- Department of Clinical Medicine (H.B., K.I., L.K., R.S.R., E.L.F.), University of Copenhagen, Copenhagen, Denmark
| | - Kasper Iversen
- Department of Clinical Medicine (H.B., K.I., L.K., R.S.R., E.L.F.), University of Copenhagen, Copenhagen, Denmark
- Department of Emergency Medicine, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark (K.I.)
| | - Niels Eske Bruun
- Department of Cardiology, Zealand University Hospital, Roskilde, Denmark (N.E.B.)
- Clinical Institutes, Copenhagen and Aalborg Universities, Aalborg, Denmark (N.E.B.)
| | - Christian H Møller
- Department of Cardiothoracic Surgery, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark (C.H.M.)
| | - Christian Tuxen
- Department of Cardiology, Bispebjerg and Frederiksberg University Hospital, Copenhagen, Denmark (C.T., R.S.R.)
| | - Helle Hjorth Johannesen
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen (M.O.F., P.H., J.L., H.H.J., A.K.ær, R.S.R.)
| | - Lars Køber
- Department of Cardiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen (K.H.-T., H.B., L.K., E.L.F.)
- Department of Clinical Medicine (H.B., K.I., L.K., R.S.R., E.L.F.), University of Copenhagen, Copenhagen, Denmark
| | - Andreas Kjær
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen (M.O.F., P.H., J.L., H.H.J., A.K.ær, R.S.R.)
- Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet & Department of Biomedical Sciences (M.O.F., A.K.ær, R.S.R.), University of Copenhagen, Copenhagen, Denmark
| | - Rasmus Sejersten Ripa
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen (M.O.F., P.H., J.L., H.H.J., A.K.ær, R.S.R.)
- Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet & Department of Biomedical Sciences (M.O.F., A.K.ær, R.S.R.), University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Medicine (H.B., K.I., L.K., R.S.R., E.L.F.), University of Copenhagen, Copenhagen, Denmark
- Department of Cardiology, Bispebjerg and Frederiksberg University Hospital, Copenhagen, Denmark (C.T., R.S.R.)
| | - Emil Loldrup Fosbøl
- Department of Cardiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen (K.H.-T., H.B., L.K., E.L.F.)
- Department of Clinical Medicine (H.B., K.I., L.K., R.S.R., E.L.F.), University of Copenhagen, Copenhagen, Denmark
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Ebbehoj A, Iversen P, Kramer S, Stochholm K, Poulsen PL, Hjorthaug K, Søndergaard E. Positron Emission Tomography Imaging of Pheochromocytoma and Paraganglioma-18F-FDOPA vs Somatostatin Analogues. J Clin Endocrinol Metab 2025; 110:303-316. [PMID: 39468778 DOI: 10.1210/clinem/dgae764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 09/19/2024] [Accepted: 10/26/2024] [Indexed: 10/30/2024]
Abstract
CONTEXT Functional imaging with positron emission tomography (PET) scans is an essential part of the diagnostic workup for pheochromocytoma and paraganglioma (PPGL). The purpose of this review is to (1) provide a brief overview of functional imaging for PPGL, (2) summarize selected present and older guideline and review recommendations, and (3) conduct a literature review on the diagnostic performance of the most used PET tracers for PPGL. EVIDENCE ACQUISITION We conducted a systematic literature search in PubMed from January 2004 to August 2024 with the search string ("Pheochromocytoma" OR "Paraganglioma") AND ("Positron Emission Tomography" OR "Radionuclide Imaging" OR ("PET" AND ("FDG" OR "DOTATOC" OR "DOTANOC" OR "DOTATATE" OR "DOPA" OR "FDOPA"))). Studies involving PET scans of at least 20 individuals with PPGL or at least 5 individuals in a rare, well-defined subgroup of PPGL (eg, sympathetic or head-neck paragangliomas and specific pathogenic variants) were included. EVIDENCE SYNTHESIS Seventy studies were identified of which 21 were head-to-head comparisons of at least 2 different PET tracers [18F-fluorodihydroxyphenylalanine, fluorodihydroxyphenylalanine positron emission tomography (18F-FDOPA), 68Ga-DOTA-conjugated somatostatin analogues, 68Ga-DOTA-conjugated somatostatin analogue positron emission tomography (68Ga-SSA), and 18F-fluorodeoxyglucose]. 18F-FDOPA had higher sensitivity for pheochromocytoma compared to 68Ga-SSA and equal sensitivity for metastatic pheochromocytoma. 18F-FDOPA and 68Ga-SSA had similar sensitivity for primary non-succinate dehydrogenase subunits (SDHx) sympathetic and head-neck paraganglioma. However, 68Ga-SSA had higher sensitivity for metastatic sympathetic and head-neck paraganglioma and for SDHx-related paraganglioma. CONCLUSION 18F-FDOPA and 68Ga-SSA PET are both sensitive for localizing PPGL. However, 18F-FDOPA is the most sensitive for detecting pheochromocytoma, while 68Ga-SSA is superior to 18F-FDOPA for metastatic sympathetic and head-neck paraganglioma and SDHx-related paraganglioma.
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Affiliation(s)
- Andreas Ebbehoj
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Peter Iversen
- Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Stine Kramer
- Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Kirstine Stochholm
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Per Løgstrup Poulsen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus N DK-8200, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Karin Hjorthaug
- Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Esben Søndergaard
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus N DK-8200, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus N DK-8200, Denmark
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Liu Y, Jiao S, Liu L, Yao S, Xu S. Predicting neuroendocrine neoplasm grade with dual tracer positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose ( 18F-FDG) and 18F-AlF-NOTA-octreotide: a lesion-based analysis. Clin Radiol 2025; 80:106715. [PMID: 39504887 DOI: 10.1016/j.crad.2024.09.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 09/17/2024] [Accepted: 09/22/2024] [Indexed: 11/08/2024]
Abstract
AIM The aim of this study was to investigate the ability of dual tracer positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose (18F-FDG) and 18F-AlF-NOTA-octreotide (18F-OC) in predicting neuroendocrine neoplasm (NEN) grade. The lesions that have been histologically confirmed were accurately located using both 18F-FDG and 18F-OC PET/CT. MATERIALS AND METHODS For each lesion, the standardized uptake value (SUV)max was measured, and tumor-to-background ratio was calculated by dividing the SUVmax by the SUVmean of background tissue at the two scans. SUVR was calculated by dividing the SUVmax of the lesion at 18F-OC PET/CT by the SUVmax at 18F-FDG PET/CT. For evaluating the correlation between continuous variables and lesion grade, the Spearman rank correlation test was used. Receiver operating characteristic (ROC) curve was used to evaluate the performance of PET/CT parameter in discriminating lesions of different grades. RESULTS A total of 49 patients (22 males, 27 females; mean age: 56.5 ± 14.3 years; range: 14-85 years) and 65 lesions were included in this study. A substantial correlation was observed between SUVR and lesion grade (rho = -0.655, p < 0.001), better than other PET/CT parameters. For discriminating G1/2 neuroendocrine tumor (NET) from G3 NET and neuroendocrine carcinoma (NEC), SUVR had the largest area under ROC curve (AUC) of 0.88. With the cut-off value of 2.217, we got the best Youden's index, 0.668. For discriminating G1/2/3 NET from NEC, SUVR and OC SUVmax had the largest AUC of 0.923. With the cut-off value of OC SUVmax of 4.35, we got the best Youden's index, 0.805. CONCLUSION This study suggests that 18F-FDG and 18F-OC PET/CT are complementary in evaluating the grade of NEN and that SUVR is a promising tool for predicting NEN grade.
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Affiliation(s)
- Y Liu
- Department of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
| | - S Jiao
- Department of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
| | - L Liu
- Department of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
| | - S Yao
- Department of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
| | - S Xu
- Department of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
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Loree JM, Chan D, Lim J, Stuart H, Fidelman N, Koea J, Posavad J, Cummins M, Doucette S, Myrehaug S, Naraev B, Bailey DL, Bellizzi A, Laidley D, Boyle V, Goodwin R, Del Rivero J, Michael M, Pasieka J, Singh S. Biomarkers to Inform Prognosis and Treatment for Unresectable or Metastatic GEP-NENs. JAMA Oncol 2024; 10:1707-1720. [PMID: 39361298 DOI: 10.1001/jamaoncol.2024.4330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2024]
Abstract
Importance Evidence-based treatment decisions for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) require individualized patient-centered decision-making that accounts for patient and cancer characteristics. Objective To create an accessible guidance document to educate clinicians and patients on biomarkers informing prognosis and treatment in unresectable or metastatic GEP-NENs. Methods A multidisciplinary panel in-person workshop was convened to define methods. English language articles published from January 2016 to January 2023 in PubMed (MEDLINE) and relevant conference abstracts were reviewed to investigate prognostic and treatment-informing features in unresectable or metastatic GEP-NENs. Data from included studies were used to form evidence-based recommendations. Quality of evidence and strength of recommendations were determined using the Grading of Recommendations, Assessment, Development and Evaluations framework. Consensus was reached via electronic survey following a modified Delphi method. Findings A total of 131 publications were identified, including 8 systematic reviews and meta-analyses, 6 randomized clinical trials, 29 prospective studies, and 88 retrospective cohort studies. After 2 rounds of surveys, 24 recommendations and 5 good clinical practice statements were developed, with full consensus among panelists. Recommendations focused on tumor and functional imaging characteristics, blood-based biomarkers, and carcinoid heart disease. A single strong recommendation was made for symptomatic carcinoid syndrome informing treatment in midgut neuroendocrine tumors. Conditional recommendations were made to use grade, morphology, primary site, and urinary 5-hydroxyindoleacetic levels to inform treatment. The guidance document was endorsed by the Commonwealth Neuroendocrine Tumour Collaboration and the North American Neuroendocrine Tumor Society. Conclusions and Relevance The study results suggest that select factors have sufficient evidence to inform care in GEP-NENs, but the evidence for most biomarkers is weak. This article may help guide management and identify gaps for future research to advance personalized medicine and improve outcomes for patients with GEP-NENs.
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Affiliation(s)
- Jonathan M Loree
- BC Cancer, Vancouver Centre, Vancouver, British Columbia, Canada
| | - David Chan
- Northern Clinical School, University of Sydney, Sydney, Australia
- ENETS Centre of Excellence, Department of Medical Oncology, Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - Jennifer Lim
- St George Hospital, Sydney, New South Wales, Australia
- University of New South Wales, Sydney, New South Wales, Australia
- Garvan Institute of Medical Research, Sydney, New South Wales, Australia
| | - Heather Stuart
- University of British Columbia and BC Cancer Agency, Vancouver, British Columbia, Canada
| | | | - Jonathan Koea
- Te Whatu Ora Waitemata and the University of Auckland, Auckland, New Zealand
| | - Jason Posavad
- Canadian Neuroendocrine Tumours Society, Cornwall, Ontario, Canada
| | | | | | - Sten Myrehaug
- Odette Cancer Centre, Toronto, Ontario, Canada
- Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
| | - Boris Naraev
- Tampa General Hospital Cancer Institute, Tampa, Florida
| | - Dale L Bailey
- Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | | | - David Laidley
- Western University, London, Ontario, Canada
- Lawson Health Research Institute, London, Ontario, Canada
| | - Veronica Boyle
- School of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
- Department of Oncology, Auckland City Hospital, Te Whatu Ora Tamaki Makaurau, Auckland, New Zealand
| | - Rachel Goodwin
- Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, Ontario, Canada
| | - Jaydi Del Rivero
- Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Michael Michael
- NET Unit and ENETS Centre of Excellence, Peter MacCallum Cancer Centre, Sir Peter MacCallum Department of Medical Oncology, University of Melbourne, Parkville, Victoria, Australia
| | - Janice Pasieka
- Section of General Surgery, Division of Endocrine Surgery and Surgical Oncology, Department of Surgery and Oncology, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
| | - Simron Singh
- University of Toronto, Toronto, Ontario, Canada
- Sunnybrook Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada
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Lamarca A, Bartsch DK, Caplin M, Kos-Kudla B, Kjaer A, Partelli S, Rinke A, Janson ET, Thirlwell C, van Velthuysen MLF, Vullierme MP, Pavel M. European Neuroendocrine Tumor Society (ENETS) 2024 guidance paper for the management of well-differentiated small intestine neuroendocrine tumours. J Neuroendocrinol 2024; 36:e13423. [PMID: 38977327 DOI: 10.1111/jne.13423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 05/28/2024] [Accepted: 06/02/2024] [Indexed: 07/10/2024]
Abstract
Both the incidence and prevalence of well-differentiated neuroendocrine tumours from the small intestine (Si-NET) are gradually increasing. Most patients have non-functioning tumours with subtle GI symptoms and tumours are often discovered incidentally by endoscopy or at advanced disease stages by imaging depicting mesenteric lymph node and /or liver metastases while around 30% of the patients present with symptoms of the carcinoid syndrome. Adequate biochemical assessment and staging including functional imaging is crucial for treatment-related decision-making that should take place in an expert multidisciplinary team setting. Preferably, patients should be referred to specialised ENETS Centres of Excellence or centres of high expertise in the field. This guidance paper provides the current evidence and best knowledge for the management of Si-NET grade (G) 1-3 following 10 key questions of practical relevance for the diagnostic and therapeutic decision making.
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Affiliation(s)
- Angela Lamarca
- Department of Oncology - Onco Health Institute, Fundación Jiménez Díaz University Hospital, Madrid, Spain
- Department of Medical Oncology, The Christie NHS Foundation, Manchester, Division of Cancer Sciences, University of Manchester, Manchester, UK
| | - Detlef K Bartsch
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps University Marburg, Marburg, Germany
| | - Martyn Caplin
- Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
| | - Beata Kos-Kudla
- Department of Endocrinology and Neuroendocrine Tumors, ENETS Center of Excellence, Department of Pathophysiology and Endocrinology, Medical University of Silesia, Katowice, Poland
| | - Andreas Kjaer
- Department of Clinical Physiology and Nuclear Medicine and Cluster for Molecular Imaging, Copenhagen University of Copenhagen-Rigshospitalet, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Stefano Partelli
- Pancreas Translational and Clinical Research Centre, Pancreatic and Transplant Surgery Unit, Vita-Salute San Raffaele University, Milan, Italy
| | - Anja Rinke
- Department of Gastroenterology, University Hospital Marburg and Philipps University Marburg, Marburg, Germany
| | - Eva Tiensuu Janson
- Department of Medical Sciences, Endocrine Oncology Unit, Uppsala University, Uppsala, Sweden
| | - Christina Thirlwell
- Department of Medical Oncology, University of Exeter Medical School, Exeter, UK
| | | | - Marie-Pierre Vullierme
- Department of Radiology, Paul Brousse University Hospital, AP-HP-University Paris Saclay, Villejuif, France
| | - Marianne Pavel
- Department of Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg, ENETS Center of Excellence Erlangen, CCC Erlangen- EMN, and Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany
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7
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Hadji-Turdeghal K, Fosbøl MØ, Hasbak P, Kjaer A, Køber L, Ripa RS, Fosbøl EL. Detection of infective endocarditis with [ 64Cu]Cu-DOTATATE positron emission tomography/computed tomography: a case series. Eur Heart J Case Rep 2024; 8:ytae431. [PMID: 39239136 PMCID: PMC11375587 DOI: 10.1093/ehjcr/ytae431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 01/08/2024] [Accepted: 08/12/2024] [Indexed: 09/07/2024]
Abstract
Background Infective endocarditis (IE) is a serious and fatal condition, with prosthetic valve endocarditis representing the worst prognosis. The recommended nuclear imaging modality 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) has limitations. In this case series, we present two patients with IE scanned with a novel PET tracer [64Cu]Cu-DOTATATE ([64Cu]Cu-[1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetra acetic acid]-d-Phe1, Tyr3-octreotate). Case summary An 84-year-old female patient (Patient 1) with a biological mitral valve prosthesis (MVP) was admitted acutely from the outpatient clinic. Transoesophageal echocardiography showed vegetations on the MVP. The patient underwent [64Cu]Cu-DOTATATE PET/CT, which showed uptake at the site of infection. The patient underwent surgical valve replacement. The post-operative period was without significant complications, and the patient was discharged home. In another case, a 72-year-old male patient (Patient 2) with a medical history of mild mitral valve stenosis, aortic valve stenosis, and gastrointestinal stromal tumour was admitted to the hospital for back and abdominal pain and subfebrile episodes. Transoesophageal echocardiography showed large vegetations in the native aortic valve. The patient underwent [64Cu]Cu-DOTATATE PET/CT, which showed no uptake at the site of the suspected infection. The patient underwent surgical valve replacement. The post-operative period was characterized by Candida albicans sternitis, and after prolonged hospitalization, the patient died of respiratory failure as a complication of sepsis. Discussion In conclusion, this is the first case series presenting two patients with definite IE (modified Duke criteria), who were scanned with the novel [64Cu]Cu-DOTATATE PET/CT. Patient 1, with endocarditis in the MVP, showed an uptake of the tracer, while Patient 2, with native aortic valve endocarditis, did not show any uptake.
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Affiliation(s)
- Katra Hadji-Turdeghal
- Department of Cardiology, Copenhagen University Hospital - Rigshospitalet, 2100 Copenhagen, Denmark
| | - Marie Øbro Fosbøl
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Rigshospitalet, 2100 Copenhagen, Denmark
- Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Philip Hasbak
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Rigshospitalet, 2100 Copenhagen, Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Rigshospitalet, 2100 Copenhagen, Denmark
- Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Lars Køber
- Department of Cardiology, Copenhagen University Hospital - Rigshospitalet, 2100 Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Rasmus Sejersten Ripa
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Rigshospitalet, 2100 Copenhagen, Denmark
- Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Emil Loldrup Fosbøl
- Department of Cardiology, Copenhagen University Hospital - Rigshospitalet, 2100 Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
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8
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Gålne A, Sundlöv A, Enqvist O, Sjögreen Gleisner K, Larsson E, Trägårdh E. Retrospective evaluation of the predictive value of tumour burden at baseline [ 68 Ga]Ga-DOTA-TOC or -TATE PET/CT and tumour dosimetry in GEP-NET patients treated with PRRT. EJNMMI REPORTS 2024; 8:24. [PMID: 39112915 PMCID: PMC11306659 DOI: 10.1186/s41824-024-00210-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 05/17/2024] [Indexed: 08/10/2024]
Abstract
PURPOSE There is a lack of validated imaging biomarkers for prediction of response to peptide receptor radionuclide therapy (PRRT). The primary objective was to evaluate if tumour burden at baseline PET/CT could predict treatment outcomes to PRRT with [177Lu]Lu-DOTA-TATE. Secondary objectives were to evaluate if there was a correlation between tumour burden and mean tumour absorbed dose (AD) during first cycle, and if mean tumour AD or the relative change of tumour burden at first follow-up PET/CT could predict progression free survival (PFS) or overall survival (OS). METHODS Patients with gastroenteropancreatic neuroendocrine tumour (GEP-NET) treated with [177Lu]Lu-DOTA-TATE PRRT were retrospectively included. Tumour burden was quantified from [68 Ga]Ga-DOTA-TOC/TATE PET/CT-images at baseline and first follow-up and expressed as; whole-body somatostatin receptor expressing tumour volume (SRETVwb), total lesion somatostatin receptor expression (TLSREwb), largest tumour lesion diameter and highest SUVmax. The relative change of tumour burden was evaluated in three categories. Mean tumour AD was estimated from the first cycle of PRRT. PFS was defined as time from start of PRRT to radiological or clinical progression. OS was evaluated as time to death. Kaplan Meier survival curves and log-rank test were used to compare PFS and OS between different groups. RESULTS Thirty-one patients had a baseline PET/CT < 6 months before treatment and 25 had a follow-up examination. Median tumour burden was 132 ml (IQR 61-302) at baseline and 71 ml (IQR 36-278) at follow-up. Twenty-two patients had disease progression (median time to progression 17.2 months) and 9 patients had no disease progression (median follow-up 28.7 months). SRETVwb dichotomized by the median at baseline was not associated with longer PFS (p = 0.861) or OS (p = 0.937). Neither TLSREwb, largest tumour lesion or SUVmax showed significant predictive value. There was a moderately strong correlation, however, between SUVmax and mean tumour AD r = 0.705, p < 0.001, but no significant correlation between SRETVwb nor TLSREwb and mean tumour AD. An increase of SRETVwb, TLSREwb or largest tumour lesion at first follow-up PET/CT was significantly correlated with shorter PFS/OS. CONCLUSION Tumour burden at baseline showed no predictive value of PFS/OS after PRRT in this small retrospective study. An increase of tumour burden was predictive of worse outcome.
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Affiliation(s)
- Anni Gålne
- Department of Medical Imaging and Physiology, Skåne University Hospital, Lund and Malmö, Sweden.
- Department of Translational Medicine, Lund University, Malmö, Sweden.
- WCMM Wallenberg Centre for Molecular Medicine, Lund, Sweden.
| | - Anna Sundlöv
- Department of Clinical Sciences, Oncology and Pathology, Skåne University Hospital, Lund University, Lund, Sweden
| | - Olof Enqvist
- Eigenvision AB, Malmö, Sweden
- Department of Electrical Engineering, Chalmers University of Technology, Gothenburg, Sweden
| | | | - Erik Larsson
- Department of Radiation Physics, Skåne University Hospital, Lund, Sweden
| | - Elin Trägårdh
- Department of Medical Imaging and Physiology, Skåne University Hospital, Lund and Malmö, Sweden
- Department of Translational Medicine, Lund University, Malmö, Sweden
- WCMM Wallenberg Centre for Molecular Medicine, Lund, Sweden
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9
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Firsova M, Treglia G, Sempoux C, Dromain C, Prior JO, Schaefer N, Boughdad S. Increased [ 68Ga]Ga-SST uptake in the uncinate pancreatic process in new digital PET/CT machine and potential association with clinical and histologic factors in NET patients. EJNMMI REPORTS 2024; 8:18. [PMID: 38910232 PMCID: PMC11194230 DOI: 10.1186/s41824-024-00203-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 04/10/2024] [Indexed: 06/25/2024]
Abstract
INTRODUCTION A physiological increase in the uptake of [68Ga]Ga-labeled somatostatin analogues ([68Ga]Ga-SST) PET tracers has been reported in the uncinate pancreatic process (UP) and might be even higher in latest generation of PET/CT scanners and might be falsely interpreted as NET. We aimed to investigate the uptake of UP in a large population of NET patients who underwent [68Ga]Ga-SST PET/CT with digital SiPM detectors. We also explored potential associations between UP uptake and various clinical, imaging, and pathological factors routinely assessed in NET patients. METHODS We analyzed all consecutive NET patients from July 2018 to June 2022 in this retrospective, single-center study. All patients underwent a [68Ga]Ga-SST PET/CT scan on a digital SiPM PET/CT scanner. On visual analysis, we distinguished between normal linear and homogenous UP uptake or abnormal if otherwise. We compared SUVmax/mean in patients with normal UP uptake to those with abnormal UP uptake with suspicious NET lesions on contrast-enhanced CT (ce-CT) and according to the site of the primary NET (pancreatic NET vs. other), patient gender (female vs. male) and tumor grade (grade 1-2 vs. 3) using a Mann-Whitney test. We also assessed the correlation between SUVmax/mean values in UP with patients' age, primary NET Ki-67 counting, and its SUVmax/mean, TLA and MTV values. RESULTS We included 131 NET patients with a total of 34 [68Ga]Ga-DOTATATE PET/CT and 113 [68Ga]Ga-DOTATOC PET/CT scans. An abnormal UP uptake was seen in 32 patients with 65.7% of suspicious NET lesion or extrinsic compression on morphological imaging. Normal UP uptake SUVmax/mean were measured in 115 [68Ga]Ga-SST scans (78.2%) with normal UP uptake and without suspicious lesion on morphological imaging. We found an average SUVmax of 12.3 ± 4.1 for [68Ga]Ga-DOTATATE and 19.8 ± 9.8 g/ml for [68Ga]Ga-DOTATOC, hence higher than those reported in the literature [SUVmax 5 ± 1.6 to 12.6 ± 2.2 g/ml] with significant difference with abnormal UP uptake and between both PET tracers (both p < 0.01). Significant results were a higher UP uptake on [68Ga]Ga-DOTATOC in male patients (p = 0.02) and significant associations between UP uptake on [68Ga]Ga-DOTATOC and SUVmax/mean of the primary tumor (ρ [0.337-0.363]; p [0.01-0.02]). CONCLUSION We confirmed a higher and very frequent UP uptake in latest SiPM-detector [68Ga]Ga-SST PET/CT with an even higher uptake in patients that had [68Ga]Ga-DOTATOC PET/CT. SUVmean/max were significantly higher in abnormal UP uptake but there were overlaps with UP SUV values for both [68Ga]Ga-SST and a correlation to morphological imaging is crucial. Besides, significant associations between UP uptake and SUVmean/max of the primary NET as well as patients' gender were seen in the larger cohort of [68Ga]Ga-DOTATOC patients suggesting that both physiological and pathological parameters could affect UP uptake.
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Affiliation(s)
- Maria Firsova
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Giorgio Treglia
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
- Clinic of Nuclear Medicine, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Via A. Gallino 12, 6500, Bellinzona, Switzerland
- Academic Education, Research and Innovation Area, General Directorate, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland
| | - Christine Sempoux
- Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
- Department of Pathology, Lausanne University Hospital, Lausanne, Switzerland
| | - Clarisse Dromain
- Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
- Department of Radiology, Lausanne University Hospital, Lausanne, Switzerland
| | - John O Prior
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Niklaus Schaefer
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Sarah Boughdad
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland.
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Ritter Z, Oeltzschner G, Solnes LB, Liu G, Kamson DO. Diagnostic and theranostic opportunities in Neuro-oncology. ADVANCES IN ONCOLOGY 2024; 4:111-124. [PMID: 40248613 PMCID: PMC12001827 DOI: 10.1016/j.yao.2024.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/19/2025]
Abstract
Theranostics, the interlinking of diagnostic and therapeutic procedures, can be particularly valuable in neuro-oncology, addressing the challenges posed by the blood-brain and brain-tumor barriers. While it is traditionally associated with nuclear medicine, advances in MR imaging techniques have opened new theranostic frontiers. This review covers the present challenges in neuro-oncology and how these could be overcome utilizing radioligand-based molecular radiotherapy as well as how label-free theranostics employing methods such as chemical exchange saturation transfer (CEST) and MR spectroscopy could advance the field.
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Affiliation(s)
- Zsombor Ritter
- The Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Hospital, Baltimore, MD
| | - Georg Oeltzschner
- Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD
- F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD
| | - Lilja Bjork Solnes
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Guanshu Liu
- Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD
- F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD
| | - David Olayinka Kamson
- The Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Hospital, Baltimore, MD
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD
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11
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Zhu C, Liu T, Yu H, Chang L, Zhang X, Yao J, Zhang G, Chen Q, He Q, Liu M. Central hyperthyroidism due to an ectopic TSH-secreting pituitary tumor: a case report and literature review. Front Endocrinol (Lausanne) 2024; 15:1301260. [PMID: 38516415 PMCID: PMC10955116 DOI: 10.3389/fendo.2024.1301260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Accepted: 02/19/2024] [Indexed: 03/23/2024] Open
Abstract
Ectopic thyroid-stimulating hormone (TSH)-secreting tumors are extremely rare, with only 15 reported cases in the literature. Herein, we described a 60-year-old female patient with thyrotoxicosis and elevated or unsuppressed levels of TSH. Family history and laboratory and genetic tests did not support a diagnosis of resistance to thyroid hormone (RTH). Given the unsuppressed TSH, TSH-secreting tumor was suspected, and magnetic resonance imaging (MRI) of the pituitary gland was performed. Surprisingly, the MRI scans revealed a nodule in the nasopharynx rather than a pituitary tumor in the sella region. Further evaluation using Gallium-68 DOTATATE positron emission tomography/computed tomography (68Ga-DOTATATE PET/CT) demonstrated increased DOTATATE uptake in the nasopharyngeal nodule. Additionally, an octreotide suppression test (OST) revealed an obvious reduction in TSH levels, further supporting the suspicion of the nasopharyngeal mass as the cause of inappropriate TSH secretion. To prepare for surgery, the patient received preoperative administration of octreotide, resulting in the normalization of TSH and thyroid hormone levels. The patient subsequently underwent successful surgical removal of the nasopharyngeal mass. Following the procedure, the patient experienced complete resolution of hyperthyroidism symptoms, with TSH declined and thyroid hormone levels returned to normal. Histochemistry analysis of the tumor revealed positive staining for TSH, growth hormone (GH), prolactin (PRL), luteinizing hormone (LH), and somatostatin receptor 2 (SSTR2). We discussed differential diagnosis of hyperthyroidism due to inappropriate TSH secretion, with a particular emphasis on the importance of 68Ga-DOTATATE PET/CT in combination with OST for identifying ectopic pituitary tumors.
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Affiliation(s)
- Chonggui Zhu
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Tong Liu
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Haonan Yu
- Department of Positron Emission Tomography/Computed Tomography (PET/CT) Examination Room, Tianjin Medical University General Hospital, Tianjin, China
| | - Lina Chang
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Xiaona Zhang
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Jia Yao
- Department of Radiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Geng Zhang
- Department of Otorhinolaryngology, Tianjin Medical University General Hospital, Tianjin, China
| | - Qiusong Chen
- Department of Positron Emission Tomography/Computed Tomography (PET/CT) Examination Room, Tianjin Medical University General Hospital, Tianjin, China
| | - Qing He
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Ming Liu
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
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12
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Kim JY, Kim J, Kim YI, Yang DH, Yoo C, Park IJ, Ryoo BY, Ryu JS, Hong SM. Somatostatin receptor 2 (SSTR2) expression is associated with better clinical outcome and prognosis in rectal neuroendocrine tumors. Sci Rep 2024; 14:4047. [PMID: 38374188 PMCID: PMC10876978 DOI: 10.1038/s41598-024-54599-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 02/14/2024] [Indexed: 02/21/2024] Open
Abstract
Somatostatin analogues have recently been used as therapeutic targets for metastatic or surgically unresectable gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), and associated somatostatin receptor (SSTR) expression has been well demonstrated in most GEP NETs, with the exception of rectal NETs. SSTR2 immunohistochemical expressions were evaluated in 350 surgically or endoscopically resected rectal NETs and compared to clinicopathologic factors. SSTR2 expression was observed in 234 (66.9%) rectal NET cases and associated tumors with smaller size (p = 0.001), low pT classification (p = 0.030), low AJCC tumor stage (p = 0.012), and absence of chromogranin expression (p = 0.009). Patients with rectal NET and SSTR2 expression had significantly better overall survival than those without SSTR2 expression both by univariable (p = 0.006) and multivariable (p = 0.014) analyses. In summary, approximately two-thirds of rectal NETs expressed SSTR2. SSTR2 expression was significantly associated with favorable behavior and good overall survival in patients with rectal NETs. Furthermore, SSTR2 expression can be used as prognostic factors. When metastatic disease occurs, SSTR2 expression can be used a possible target for somatostatin analogues.
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Affiliation(s)
- Joo Young Kim
- Department of Pathology, Chung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul, Republic of Korea
| | - Jisup Kim
- Department of Pathology, Gil Medical Center, Gachon University College of Medicine, Inchon, Republic of Korea
| | - Yong-Il Kim
- Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dong-Hoon Yang
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Changhoon Yoo
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - In Ja Park
- Departments of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Baek-Yeol Ryoo
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jin-Sook Ryu
- Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
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13
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Schmidt M, Hinterleitner C, Singer S, Lauer UM, Zender L, Hinterleitner M. Diagnostic Approaches for Neuroendocrine Neoplasms of Unknown Primary (NEN-UPs) and Their Prognostic Relevance-A Retrospective, Long-Term Single-Center Experience. Cancers (Basel) 2023; 15:4316. [PMID: 37686593 PMCID: PMC10486951 DOI: 10.3390/cancers15174316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/18/2023] [Accepted: 08/25/2023] [Indexed: 09/10/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) represent a rare and heterogenous group of tumors with predominantly gastroenteropancreatic or pulmonary origin. Despite numerous diagnostic efforts, the primary tumor site remains unknown in up to 20% of the patients diagnosed with NEN. In this subgroup of NEN patients, a standard diagnostic algorithm has not yet been integrated into clinical routine. Of note, an undetermined primary tumor site in NENs is associated with an impaired clinical outcome by at least "formally" limiting treatment options exclusively approved for NENs of a certain histological origin. In this retrospective study, a patient cohort of 113 patients initially diagnosed with NEN of unknown primary (NEN-UP) was analyzed. In 13 patients (11.5%) a primary tumor site could be identified subsequently, amongst others, by performing somatostatin receptor (SSTR)-PET-based imaging, which was irrespective of the initial clinical or demographic features. Diagnostic work-up and therapeutic regimens did not differ significantly between patients with an identified or unidentified primary tumor site; only a detailed immunohistochemical assessment providing additional information on the tumor origin proved to be significantly associated with the detection of a primary tumor site. Our study revealed that a profound diagnostic work-up, particularly including SSTR-PET-based imaging, leads to additional treatment options, finally resulting in significantly improved clinical outcomes for patients with NEN-UPs.
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Affiliation(s)
- Moritz Schmidt
- Department of Medical Oncology & Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076 Tuebingen, Germany
- ENETS Center of Excellence, University Hospital Tuebingen, Otfried-Mueller-Str. 14, 72076 Tuebingen, Germany;
- DFG Cluster of Excellence 2180 ‘Image-Guided and Functional Instructed Tumor Therapy’ (iFIT), University of Tuebingen, 72076 Tuebingen, Germany
| | - Clemens Hinterleitner
- Department of Medical Oncology & Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076 Tuebingen, Germany
- ENETS Center of Excellence, University Hospital Tuebingen, Otfried-Mueller-Str. 14, 72076 Tuebingen, Germany;
- DFG Cluster of Excellence 2180 ‘Image-Guided and Functional Instructed Tumor Therapy’ (iFIT), University of Tuebingen, 72076 Tuebingen, Germany
- Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Stephan Singer
- ENETS Center of Excellence, University Hospital Tuebingen, Otfried-Mueller-Str. 14, 72076 Tuebingen, Germany;
- Department of Pathology, University Hospital Tuebingen, 72076 Tuebingen, Germany
| | - Ulrich M. Lauer
- Department of Medical Oncology & Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076 Tuebingen, Germany
- ENETS Center of Excellence, University Hospital Tuebingen, Otfried-Mueller-Str. 14, 72076 Tuebingen, Germany;
- DFG Cluster of Excellence 2180 ‘Image-Guided and Functional Instructed Tumor Therapy’ (iFIT), University of Tuebingen, 72076 Tuebingen, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 72076 Tuebingen, Germany
| | - Lars Zender
- Department of Medical Oncology & Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076 Tuebingen, Germany
- ENETS Center of Excellence, University Hospital Tuebingen, Otfried-Mueller-Str. 14, 72076 Tuebingen, Germany;
- DFG Cluster of Excellence 2180 ‘Image-Guided and Functional Instructed Tumor Therapy’ (iFIT), University of Tuebingen, 72076 Tuebingen, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 72076 Tuebingen, Germany
| | - Martina Hinterleitner
- Department of Medical Oncology & Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076 Tuebingen, Germany
- ENETS Center of Excellence, University Hospital Tuebingen, Otfried-Mueller-Str. 14, 72076 Tuebingen, Germany;
- DFG Cluster of Excellence 2180 ‘Image-Guided and Functional Instructed Tumor Therapy’ (iFIT), University of Tuebingen, 72076 Tuebingen, Germany
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Petranović Ovčariček P, Campenni A, de Keizer B, Deandreis D, Kreissl MC, Vrachimis A, Tuncel M, Giovanella L. Molecular Theranostics in Radioiodine-Refractory Differentiated Thyroid Cancer. Cancers (Basel) 2023; 15:4290. [PMID: 37686566 PMCID: PMC10486510 DOI: 10.3390/cancers15174290] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 08/14/2023] [Accepted: 08/25/2023] [Indexed: 09/10/2023] Open
Abstract
Differentiated thyroid cancer (DTC) is the most common subtype of thyroid cancer and has an excellent overall prognosis. However, metastatic DTC in certain cases may have a poor prognosis as it becomes radioiodine-refractory. Molecular imaging is essential for disease evaluation and further management. The most commonly used tracers are [18F]FDG and isotopes of radioiodine. Several other radiopharmaceuticals may be used as well, with different diagnostic performances. This review article aims to summarize radiopharmaceuticals used in patients with radioiodine-refractory DTC (RAI-R DTC), focusing on their different molecular pathways. Additionally, it will demonstrate possible applications of the theranostics approach to this subgroup of metastatic DTC.
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Affiliation(s)
- Petra Petranović Ovčariček
- Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Alfredo Campenni
- Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, 98100 Messina, Italy;
| | - Bart de Keizer
- Department of Nuclear Medicine and Radiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands;
| | | | - Michael C. Kreissl
- Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Otto-von-Guericke University, 39120 Magdeburg, Germany;
| | - Alexis Vrachimis
- Department of Nuclear Medicine, German Oncology Center, University Hospital of the European University, Limassol 4108, Cyprus;
| | - Murat Tuncel
- Department of Nuclear Medicine, Hacettepe University, Ankara 06230, Turkey;
| | - Luca Giovanella
- Clinic for Nuclear Medicine, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland;
- Clinic for Nuclear Medicine, University Hospital of Zürich, 8004 Zürich, Switzerland
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15
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Panzuto F, Ramage J, Pritchard DM, van Velthuysen MLF, Schrader J, Begum N, Sundin A, Falconi M, O'Toole D. European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for gastroduodenal neuroendocrine tumours (NETs) G1-G3. J Neuroendocrinol 2023; 35:e13306. [PMID: 37401795 DOI: 10.1111/jne.13306] [Citation(s) in RCA: 53] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 05/09/2023] [Accepted: 05/10/2023] [Indexed: 07/05/2023]
Abstract
The aim of the present guidance paper was to update the previous ENETS guidelines on well-differentiated gastric and duodenal neuroendocrine tumours (NETs), providing practical guidance for specialists in the diagnosis and management of gastroduodenal NETs. Type II gastric NETs, neuroendocrine carcinomas (NECs), and functioning duodenal NETs are not covered, since they will be discussed in other ENETS guidance papers.
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Affiliation(s)
- Francesco Panzuto
- Department of Medical-Surgical Sciences and Translational Medicine, Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - John Ramage
- Department of Gastroenterology, Hampshire Hospitals and ENETS Center, Kings Health Partners London, London, United Kingdom
| | - D Mark Pritchard
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | | | - Joerg Schrader
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Nehara Begum
- Department for General-, Visceral-, Thoracic- and Endocrine Surgery, Johannes-Wesling-Klinikum Minden, University Hospital of the Ruhr-University Bochum, Bochum, Germany
| | - Anders Sundin
- Department of Surgical Sciences, Radiology & Molecular Imaging, Uppsala University, Uppsala, Sweden
| | - Massimo Falconi
- Pancreas Translational and Clinical Research Center, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Dermot O'Toole
- National Centre for Neuroendocrine Tumours, ENETS Centre of Excellence, St. Vincent's University Hospital, Dublin, Ireland
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Jensen JK, Madsen JS, Jensen MEK, Kjaer A, Ripa RS. [ 64Cu]Cu-DOTATATE PET metrics in the investigation of atherosclerotic inflammation in humans. J Nucl Cardiol 2023; 30:986-1000. [PMID: 36045250 PMCID: PMC10261263 DOI: 10.1007/s12350-022-03084-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 07/19/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE The aim of this study was to assess and compare the arterial uptake of the inflammatory macrophage targeting PET tracer [64Cu]Cu-DOTATATE in patients with no or known cardiovascular disease (CVD) to investigate potential differences in uptake. METHODS Seventy-nine patients who had undergone [64Cu]Cu-DOTATATE PET/CT imaging for neuroendocrine neoplasm disease were retrospectively allocated to three groups: controls with no known CVD risk factors (n = 22), patients with CVD risk factors (n = 24), or patients with known ischemic CVD (n = 33). Both maximum, mean of max and most-diseased segment (mds) standardized uptake value (SUV) and target-to-background ratio (TBR) uptake metrics were measured and reported for the carotid arteries and the aorta. To assess reproducibility between different reviewers, Bland-Altman plots were made. RESULTS For the carotid arteries, SUVmax (P = .03), SUVmds (0.05), TBRmax (P < .01), TBRmds (P < .01), and mean-of-max TBR (P = .01) were overall shown to provide a group-wise difference in uptake. When measuring uptake values in the aorta, a group-wise difference was only observed with TBRmds (P = .04). Overall, reproducibility of the reported uptake metrics was excellent for SUVs and good to excellent for TBRs for both the carotid arteries and the aorta. CONCLUSION Using [64Cu]Cu-DOTATATE PET imaging as a marker of atherosclerotic inflammation, we were able to demonstrate differences in some of the most frequently reported uptake metrics in patients with different degrees of CVD. Measurements of the carotid artery as either maximum uptake values or most-diseased segment analysis showed the best ability to discriminate between the groups.
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Affiliation(s)
- Jacob K. Jensen
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital – Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
- Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Johanne S. Madsen
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital – Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
- Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Malte E. K. Jensen
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital – Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
- Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital – Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
- Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Rasmus S. Ripa
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital – Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
- Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
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17
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Targeting of Glucose Transport and the NAD Pathway in Neuroendocrine Tumor (NET) Cells Reveals New Treatment Options. Cancers (Basel) 2023; 15:cancers15051415. [PMID: 36900207 PMCID: PMC10001048 DOI: 10.3390/cancers15051415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/12/2023] [Accepted: 02/18/2023] [Indexed: 02/25/2023] Open
Abstract
(1) Background: the potency of drugs that interfere with glucose metabolism, i.e., glucose transporters (GLUT) and nicotinamide phosphoribosyltransferase (NAMPT) was analyzed in neuroendocrine tumor (NET, BON-1, and QPG-1 cells) and small cell lung cancer (SCLC, GLC-2, and GLC-36 cells) tumor cell lines. (2) Methods: the proliferation and survival rate of tumor cells was significantly affected by the GLUT-inhibitors fasentin and WZB1127, as well as by the NAMPT inhibitors GMX1778 and STF-31. (3) Results: none of the NET cell lines that were treated with NAMPT inhibitors could be rescued with nicotinic acid (usage of the Preiss-Handler salvage pathway), although NAPRT expression could be detected in two NET cell lines. We finally analyzed the specificity of GMX1778 and STF-31 in NET cells in glucose uptake experiments. As previously shown for STF-31 in a panel NET-excluding tumor cell lines, both drugs specifically inhibited glucose uptake at higher (50 μM), but not at lower (5 μM) concentrations. (4) Conclusions: our data suggest that GLUT and especially NAMPT inhibitors are potential candidates for the treatment of NET tumors.
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18
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Galldiks N, Hattingen E, Langen KJ, Tonn JC. Imaging Characteristics of Meningiomas. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1416:21-33. [PMID: 37432617 DOI: 10.1007/978-3-031-29750-2_3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 07/12/2023]
Abstract
Contemporary neuroimaging of meningiomas has largely relied on computed tomography, and more recently magnetic resonance imaging. While these modalities are frequently used in nearly all clinical settings where meningiomas are treated for the routine diagnosis and follow-up of these tumors, advances in neuroimaging have provided novel opportunities for prognostication and treatment planning (including both surgical planning and radiotherapy planning). These include perfusion MRIs, and positron emission tomography (PET) imaging modalities. Here we will summarize the contemporary uses for neuroimaging in meningiomas, and future applications of novel, cutting edge imaging techniques that may be routinely implemented in the future to enable more precise treatment of these challenging tumors.
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Affiliation(s)
- Norbert Galldiks
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
- Institute of Neuroscience and Medicine (INM-3, -4), Research Center Juelich, Juelich, Germany.
- Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne, and Duesseldorf, Aachen, Germany.
| | - Elke Hattingen
- Institute of Neuroradiology, Goethe University Hospital, Frankfurt am Main, Germany
| | - Karl-Josef Langen
- Institute of Neuroscience and Medicine (INM-3, -4), Research Center Juelich, Juelich, Germany
- Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne, and Duesseldorf, Aachen, Germany
- Department of Nuclear Medicine, University Hospital Aachen, Aachen, Germany
| | - Jörg C Tonn
- Department of Neurosurgery, Ludwig Maximilians-University of Munich (LMU), Munich, Germany
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19
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Koffas A, Giakoustidis A, Papaefthymiou A, Bangeas P, Giakoustidis D, Papadopoulos VN, Toumpanakis C. Diagnostic work-up and advancement in the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. Front Surg 2023; 10:1064145. [PMID: 36950054 PMCID: PMC10025557 DOI: 10.3389/fsurg.2023.1064145] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 02/07/2023] [Indexed: 03/08/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms ranging from well-differentiated, slowly growing tumors to poorly differentiated carcinomas. These tumors are generally characterized by indolent course and quite often absence of specific symptoms, thus eluding diagnosis until at an advanced stage. This underscores the importance of establishing a prompt and accurate diagnosis. The gold-standard remains histopathology. This should contain neuroendocrine-specific markers, such as chromogranin A; and also, an estimate of the proliferation by Ki-67 (or MIB-1), which is pivotal for treatment selection and prognostication. Initial work-up involves assessment of serum Chromogranin A and in selected patients gut peptide hormones. More recently, the measurement of multiple NEN-related transcripts, or the detection of circulating tumor cells enhanced our current diagnostic armamentarium and appears to supersede historical serum markers, such as Chromogranin A. Standard imaging procedures include cross-sectional imaging, either computed tomography or magnetic resonance, and are combined with somatostatin receptor scintigraphy. In particular, the advent of 111In-DTPA-octreotide and more recently PET/CT and 68Ga-DOTA-Octreotate scans revolutionized the diagnostic landscape of NENs. Likewise, FDG PET represents an invaluable asset in the management of high-grade neuroendocrine carcinomas. Lastly, endoscopy, either conventional, or more advanced modalities such as endoscopic ultrasound, capsule endoscopy and enteroscopy, are essential for the diagnosis and staging of gastroenteropancreatic neuroendocrine neoplasms and are routinely integrated in clinical practice. The complexity and variability of NENs necessitate the deep understanding of the current diagnostic strategies, which in turn assists in offering optimal patient-tailored treatment. The current review article presents the diagnostic work-up of GEP-NENs and all the recent advances in the field.
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Affiliation(s)
- Apostolos Koffas
- Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
- Correspondence: Apostolos Koffas
| | - Alexandros Giakoustidis
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Apostolis Papaefthymiou
- Pancreaticobiliary Medicine Unit, University College London Hospitals (UCLH), London, United Kingdom
| | - Petros Bangeas
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Dimitrios Giakoustidis
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Vasileios N Papadopoulos
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Christos Toumpanakis
- Centre for Gastroenterology, Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, United Kingdom
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20
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Resch K, Hung R, Abele J. Gastrointestinal neuroendocrine tumor with discordant metastatic disease on 111In-pentetreotide SPECT/CT, 18F-DOPA PET/CT and 68Ga-HA-DOTATATE PET/CT. Eur J Hybrid Imaging 2022; 6:13. [PMID: 35781170 PMCID: PMC9250908 DOI: 10.1186/s41824-022-00134-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 03/31/2022] [Indexed: 11/10/2022] Open
Abstract
AbstractA 62-year-old man with resected, pathology-proven small bowel neuroendocrine tumor underwent 111In-pentetreotide SPECT/CT, 18F-DOPA PET/CT and 68Ga-HA-DOTATATE PET/CT to assess metastatic disease. The 111In-pentetreotide SPECT/CT scan showed no metastatic disease. Both 18F-DOPA and 68Ga-HA-DOTATATE PET/CT showed hepatic and peritoneal metastatic disease. However, the burden of 18F-DOPA-avid metastatic disease was far greater compared to the burden of 68Ga-HA-DOTATATE-avid metastatic disease.
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21
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Poletto G, Cecchin D, Sperti S, Filippi L, Realdon N, Evangelista L. Head-to-Head Comparison between Peptide-Based Radiopharmaceutical for PET and SPECT in the Evaluation of Neuroendocrine Tumors: A Systematic Review. Curr Issues Mol Biol 2022; 44:5516-5530. [PMID: 36354685 PMCID: PMC9689511 DOI: 10.3390/cimb44110373] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 11/03/2022] [Accepted: 11/04/2022] [Indexed: 08/04/2023] Open
Abstract
We compared head-to-head the most used radiolabeled peptides for single photon computed emission tomography (SPECT) and positron emission tomography (PET) imaging of neuroendocrine tumors (NETs). A comprehensive literature search was performed in PubMed, Web of Science, and Scopus databases. The following words, coupled two by two, were used: 68Ga-DOTATOC; 68Ga-DOTATATE; 68Ga-DOTANOC; 99mTc-EDDA/HYNIC-TOC; 64Cu-DOTATATE; and 111In-DTPA-octreotide. Moreover, a second-step search strategy was adopted by using the following combined terms: "Somatostatin receptor imaging,"; "Somatostatin receptor imaging" and "Functional,"; "Somatostatin receptor imaging" and "SPECT,"; and "Somatostatin receptor imaging" and "PET". Eligible criteria were: (1) original articles focusing on the clinical application of the radiopharmaceutical agents in NETs; (2) original articles in the English language; (3) comparative studies (head-to-head comparative or matched-paired studies). Editorials, letters to the editor, reviews, pictorial essays, clinical cases, or opinions were excluded. A total of 1077 articles were found in the three electronic databases. The full texts of 104 articles were assessed for eligibility. Nineteen articles were finally included. Most articles focused on the comparison between 111In-DTPA-Octreotide and 68Ga-DOTATOC/TATE. Few papers compared 64Cu-DOTATATE and 68Ga-DOTATOC/TATE, or SPECT tracers. The rates of true positivity were 63.7%, 58.5%, 78.4% and 82.4%, respectively, for 111In-DTPA-Octreotide, 99mTc-EDDA/HYNIC-TOC, 68Ga-DOTATATE/TOC and 64Cu-DOTATATE. In conclusion, as highly expected, PET tracers are more suitable for the in vivo identification of NETs. Indeed, in comparative studies, they demonstrated a higher true positive rate than SPECT agents.
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Affiliation(s)
- Giulia Poletto
- Nuclear Medicine Unit, Department of Medicine DIMED, University of Padua, 35128 Padua, Italy
| | - Diego Cecchin
- Nuclear Medicine Unit, Department of Medicine DIMED, University of Padua, 35128 Padua, Italy
| | - Stefania Sperti
- Nuclear Medicine Unit, Department of Medicine DIMED, University of Padua, 35128 Padua, Italy
| | - Luca Filippi
- Department of Nuclear Medicine, Santa Maria Goretti Hospital, 04100 Latina, Italy
| | - Nicola Realdon
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy
| | - Laura Evangelista
- Nuclear Medicine Unit, Department of Medicine DIMED, University of Padua, 35128 Padua, Italy
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22
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Bentestuen M, Gossili F, Almasi CE, Zacho HD. Prevalence and significance of incidental findings on 68 Ga-DOTA-conjugated somatostatin receptor-targeting peptide PET/CT: a systematic review of the literature. Cancer Imaging 2022; 22:44. [PMID: 36057635 PMCID: PMC9441055 DOI: 10.1186/s40644-022-00484-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 08/23/2022] [Indexed: 11/17/2022] Open
Abstract
Aim We aimed to evaluate the prevalence of incidental 68 Ga-DOTA-conjugated somatostatin receptor-targeting peptide PET/CT (SSTR PET/CT) findings, their clinical significance in the need for follow-up, and their risk of malignancy. Materials and methods Studies reporting incidental SSTR PET/CT findings were systematically searched in PubMed, Cochrane, Embase and Web of Science literature published prior to 1st of May 2020. Studies were filtered by two independent readers for eligibility based on title and abstract, and subsequently on full text. The main exclusion criteria were: 1) pathological findings that matched scan indication, 2) known organ specific disease and/or incidental findings confirmed on other scan modality prior to SSTR PET/CT, 3) lack of diagnosis and/or follow up, and 4) results published in proceedings or conference abstracts. Results Twenty-one studies, comprising a total of 2906 subjects, were eligible for the analysis. Studies included were retrospective cohort studies on incidental SSTR PET/CT findings in a specific organ (n = 2888, 7/21) or case reports (n = 18, 14/21). A total of 133 subjects had incidental SSTR PET/CT findings. Incidental findings were predominantly seen in the thyroid gland (n = 65), spine (n = 30), brain (n = 26) and breast (n = 6). Seventeen of 133 (13%) incidental findings were malignant on final diagnosis. Incidental breast findings were associated with the highest risk of malignancy (67%). In the thyroid, incidental SSTR uptake was caused by malignancy in 8%, all presenting as focal uptake. The lowest risk was seen in the spine with a malignancy rate of 3% in patients with incidental SSTR uptake and benign cases were interpreted as vertebral hemangiomas on CT. Incidental SSTR PET/CT findings in other locations were of malignant etiology in two out of six cases (33%) and should be evaluated individually. Conclusion The most incidental SSTR PET/CT findings were found in the thyroid gland, spine, and brain. The risk of malignancy was greatest in incidental SSTR PET/CT findings in the breast, cranially, and thyroid gland. The results of the present study can prove useful in the interpretation of atypical findings on SSTR PET/CT and in the counseling of clinicians. Supplementary Information The online version contains supplementary material available at 10.1186/s40644-022-00484-0.
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Affiliation(s)
- Morten Bentestuen
- Department of Nuclear Medicine and Clinical Cancer Research Center, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark.
| | - Farid Gossili
- Department of Nuclear Medicine and Clinical Cancer Research Center, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark
| | - Charlotte Elberling Almasi
- Department of Nuclear Medicine and Clinical Cancer Research Center, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark
| | - Helle Damgaard Zacho
- Department of Nuclear Medicine and Clinical Cancer Research Center, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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23
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Positron Emission Tomography Radiopharmaceuticals in Differentiated Thyroid Cancer. Molecules 2022; 27:molecules27154936. [PMID: 35956886 PMCID: PMC9370596 DOI: 10.3390/molecules27154936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 08/01/2022] [Accepted: 08/01/2022] [Indexed: 11/29/2022] Open
Abstract
Differentiated thyroid cancer (DTC), arising from thyroid follicular epithelial cells, is the most common type of thyroid cancer. Despite the well-known utilization of radioiodine treatment in DTC, i.e., iodine-131, radioiodine imaging in DTC is typically performed with iodine-123 and iodine-131, with the current hybrid scanner performing single photon emission tomography/computed tomography (SPECT/CT). Positron emission tomography/computed tomography (PET/CT) provides superior visualization and quantification of functions at the molecular level; thus, lesion assessment can be improved compared to that of SPECT/CT. Various types of cancer, including radioiodine-refractory DTC, can be detected by 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), the most well-known and widely used PET radiopharmaceutical. Several other PET radiopharmaceuticals have been developed, although some are limited in availability despite their potential clinical utilizations. This article aims to summarize PET radiopharmaceuticals in DTC, focusing on molecular pathways and applications.
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24
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Refardt J, Hofland J, Wild D, Christ E. Molecular Imaging of Neuroendocrine Neoplasms. J Clin Endocrinol Metab 2022; 107:e2662-e2670. [PMID: 35380158 DOI: 10.1210/clinem/dgac207] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Indexed: 12/17/2022]
Abstract
The key for molecular imaging is the use of a radiotracer with a radioactive and a functional component. While the functional component targets a specific feature of the tumor, the radioactive component makes the target visible. Neuroendocrine neoplasms (NEN) are a diverse group of rare tumors that arise from neuroendocrine cells found mainly in the gastroenteropancreatic system, lung, thyroid, and adrenal glands. They are characterized by the expression of specific hormone receptors on the tumor cell surface, which makes them ideal targets for radiolabeled peptides. The most commonly expressed hormone receptors on NEN cells are the somatostatin receptors. They can be targeted for molecular imaging with various radiolabeled somatostatin analogs, but also with somatostatin antagonists, which have shown improved imaging quality. 18F-DOPA imaging has become a second-line imaging modality in NENs, with the exception of the evaluation of advanced medullary thyroid carcinoma. Alternatives for NENs with insufficient somatostatin receptor expression due to poor differentiation involve targeting glucose metabolism, which can also be used for prognosis. For the localization of the often-small insulinoma, glucagon-like peptide-1 (GLP-1) receptor imaging has become the new standard. Other alternatives involve metaiodobenzylguanidine and the molecular target C-X-C motif chemokine receptor-4. In addition, new radiopeptides targeting the fibroblast activation protein, the glucose-dependent insulinotropic polypeptide receptor and cholecystokinin-2 receptors have been identified in NENs and await further evaluation. This mini-review aims to provide an overview of the major molecular imaging modalities currently used in the field of NENs, and also to provide an outlook on future developments.
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Affiliation(s)
- Julie Refardt
- Department of Internal Medicine, Section of Endocrinology, ENETS Center of Excellence, Erasmus Medical Center, Rotterdam, the Netherlands
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland
- Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
| | - Johannes Hofland
- Department of Internal Medicine, Section of Endocrinology, ENETS Center of Excellence, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Damian Wild
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland
- Division of Nuclear Medicine, University Hospital Basel, Basel, Switzerland
| | - Emanuel Christ
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland
- Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
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25
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Jiang Y, Liu Q, Wang G, Sui H, Wang R, Wang J, Zhu Z. A prospective head-to-head comparison of 68 Ga-NOTA-3P-TATE-RGD and 68 Ga-DOTATATE in patients with gastroenteropancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2022; 49:4218-4227. [PMID: 35657429 DOI: 10.1007/s00259-022-05852-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 05/24/2022] [Indexed: 11/30/2022]
Abstract
PURPOSE The aim of this study was to compare 68 Ga-NOTA-3P-TATE-RGD, a dual somatostatin receptor 2- and integrin αVβ3-targeting tracer, to 68 Ga-DOTATATE in a single group of patients with gastroenteropancreatic (GEP)-neuroendocrine tumours (NETs). METHODS Thirty-five patients with histologically confirmed GEP-NETs (5 grade 1, 28 grade 2, and 2 grade 3 tumours) were prospectively enrolled with informed consent. The primary tumour mainly originated from the pancreas and rectum. All patients were scanned with both 68 Ga-NOTA-3P-TATE-RGD PET/CT and 68 Ga-DOTATATE PET/CT within a week and compared on a head-to-head basis. Sixteen patients also had conventional 18F-FDG PET/CT. Images were evaluated semi-quantitatively using maximum standardized uptake values (SUVmax) of tumour and tumour-to-background ratio. RESULTS All patients had at least one positive lesion on each of the two scans. A total of 1190 and 1106 lesions were detected on 68 Ga-NOTA-3P-TATE-RGD images and 68 Ga-DOTATATE images, respectively (P = 0.152). 68 Ga-NOTA-3P-TATE-RGD PET/CT revealed significantly more lesions in the liver than 68 Ga-DOTATATE PET/CT (634 vs. 532, P = 0.021). Both tracers produced comparable results for detecting primary tumours (20 vs. 20, P = 1.000), lymph node metastases (101 vs. 102, P = 0.655), and bone metastases (381 vs. 398, P = 0.244). The tumour SUVmax in 12 patients was significantly higher for 68 Ga-NOTA-3P-TATE-RGD than for 68 Ga-DOTATATE (27.2 ± 13.6 vs. 19.5 ± 10.0, P < 0.001); among them, 9 had 18F-FDG PET/CT and all were found to be FDG-positive. The remaining 23 patients had significantly higher 68 Ga-DOTATATE uptake than 68 Ga-NOTA-3P-TATE-RGD uptake (22.3 ± 16.4 vs. 11.9 ± 7.5, P < 0.001); among them, 7 had 18F-FDG PET/CT and 6 were FDG-negative. Generally, 68 Ga-DOTATATE demonstrated higher tumour SUVmax than 68 Ga-NOTA-3P-TATE-RGD (20.8 ± 16.0 vs. 14.2 ± 8.9, P < 0.001), including primary tumours, liver lesions, lymph node lesions, and bone lesions. However, the tumour-to-background ratio of liver lesions was significantly higher when using 68 Ga-NOTA-3P-TATE-RGD compared with that when using 68 Ga-DOTATATE (8.4 ± 5.5 vs. 4.7 ± 3.7, P < 0.001). CONCLUSION 68 Ga-NOTA-3P-TATE-RGD performed better than 68 Ga-DOTATATE in detection of liver metastases with a higher tumour-to-background ratio. Moreover, 68 Ga-NOTA-3P-TATE-RGD tended to demonstrate higher uptake over 68 Ga-DOTATATE in FDG-avid NETs. TRIAL REGISTRATION Dual SSTR2 and Integrin αvβ3 Targeting PET/CT Imaging (NCT02817945, registered 5 November 2018). URL OF REGISTRY: https://clinicaltrials.gov/ct2/show/NCT02817945.
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Affiliation(s)
- Yuanyuan Jiang
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.,State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China
| | - Qingxing Liu
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.,State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China
| | - Guochang Wang
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.,State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China
| | - Huimin Sui
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.,State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China
| | - Rongxi Wang
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.,State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China
| | - Jiarou Wang
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.,State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China
| | - Zhaohui Zhu
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. .,State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China.
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26
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Christ E, Wild D, Refardt J. Molecular Imaging in neuroendocrine neoplasias. Presse Med 2022; 51:104115. [PMID: 35131317 DOI: 10.1016/j.lpm.2022.104115] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 01/11/2022] [Accepted: 01/28/2022] [Indexed: 12/16/2022] Open
Abstract
Molecular imaging, which uses molecular targets due to the overexpression of specific peptide hormone receptors on the tumour surface, has become an indispensable diagnostic technique. Neuroendocrine neoplasms (NENs) especially differentiated NENs or neuroendocrine tumours (NETs) are a rare group of heterogeneous tumours, characterized by the expression of hormone receptors on the tumour cell surface. This property makes them receptive to diagnostic and therapeutic approaches (theranostics) using radiolabelled peptides. Amongst the known hormone receptors, somatostatin receptors (SSTR) are expressed on the majority of NETs and are therefore the most relevant receptors for theranostic approaches. Current research aims to medically upregulate their expression, while other focuses are on the use of different radiopeptides (64Cu and 67Cu) or somatostatin-antagonists instead of the established somatostatin agonists. The GLP-1 receptor is another clinically relevant target, as GLP-1-R imaging has become the new standard for the localisation of insulinomas. For staging and prognostic evaluation in dedifferentiated NENs, 18F-FDG-imaging is useful, but lacks a therapeutic counterpart. Further options for patients with insufficient expression of SSTR involve metaiodobenzylguanidine (MIBG) and the molecular target C-X-C motif chemokine receptor-4 (CXCR4). New targets such as the glucose-dependant insulinotropic polypeptide receptor (GIPR) and the fibroblast activation protein (FAP) have been identified in NENs recently and await further evaluation. For medullary thyroid cancer 18-F-DOPA imaging is standard, however this technique is rather second line for other NENs. In this area, the discovery of minigastrin, which targets the cholecystokinin-2 (CCK2) receptors in medullary thyroid carcinoma and foregut NENs, may improve future management. This review aims to provide an overview of the most commonly used functional imaging modalities for theranostics in NENs today and in the possible future.
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Affiliation(s)
- Emanuel Christ
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland; Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
| | - Damian Wild
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland; Division of Nuclear Medicine, University Hospital Basel, Basel, Switzerland
| | - Julie Refardt
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland; Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
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Anzola LK, Lauri C, Granados CE, Laganà B, Signore A. Uptake pattern of [68Ga]Ga-DOTA-NOC in tissues: implications for inflammatory diseases. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2022; 66:156-161. [PMID: 31833738 DOI: 10.23736/s1824-4785.19.03178-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND [68Ga]Ga-DOTA-NOC binds to somatostatin receptor (SSTR) subtypes 2 and 5, also expressed on lymphocytes and macrophages, but no information is available about uptake in tissues that might be affected by a chronic inflammatory process. Our aim was to obtain normal reference values for: [68Ga]Ga-DOTA-NOC uptake in tissues prone to chronic inflammation. METHODS Retrospective study in 81 patients who performed the scan for a suspicion of neuroendocrine tumor (NET). We analyzed major joints, salivary glands, thyroid, aortic wall from images acquired after injection of 173.9±1 Mbq of: [68Ga]Ga-DOTA-NOC. We calculated the SUV<inf>max</inf> and SUV<inf>target</inf>/SUV<inf>gluteus</inf> ratio or SUV<inf>target</inf>/SUV<inf>aorta</inf> ratio. Data are reported as mean±2 or ±3 standard deviations (SD). RESULTS SUV<inf>max</inf> values appeared more reliable than other ratios. In thyroid we found a mean SUV<inf>max</inf> of 1.36±0.45, with no values >3SD; in parotid glands 0.98±0.40, with 2 values >3SD; in submandibular glands 0.99±0.37, with 2 values >3SD; in aortic arch 1.71±0.50, with 1 value >3SD; in thoracic aorta 2.03±0.52, with 1 value >3SD; in abdominal aorta 2.19±0.49, with no value >3SD; in shoulders 0.92±0.31 and in hips 0.87±0.34, with 2 and 4 values >3SD, respectively. These 12 values with SUV<inf>max</inf> >3SD, belong to 5 patients, 3 of which had signs of xerostomia and/or arthritis. A statistically significant correlation was observed between SUV<inf>max</inf> and age in all examined tissues but in the aorta. CONCLUSIONS Tissues in which lymphocytic infiltration may occur show that SUV<inf>max</inf> is tissue-dependent. Within tissue variability, an SUV<inf>max</inf> greater than the mean +3SD is rarely found amongst patients without a symptomatic chronic inflammatory process but, when found, may highlight a chronic inflammatory condition.
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Affiliation(s)
- Luz K Anzola
- Unit of Nuclear Medicine, Clinica Colsanitas, Bogotà, Colombia - .,Unit of Nuclear Medicine, Department of Medical-Surgical Sciences and of Translational Medicine, Sapienza University, Rome, Italy - .,Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands -
| | - Chiara Lauri
- Unit of Nuclear Medicine, Department of Medical-Surgical Sciences and of Translational Medicine, Sapienza University, Rome, Italy
| | | | - Bruno Laganà
- Unit of Rheumatology, Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy
| | - Alberto Signore
- Unit of Nuclear Medicine, Department of Medical-Surgical Sciences and of Translational Medicine, Sapienza University, Rome, Italy.,Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
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Vahidfar N, Farzanehfar S, Abbasi M, Mirzaei S, Delpassand ES, Abbaspour F, Salehi Y, Biersack HJ, Ahmadzadehfar H. Diagnostic Value of Radiolabelled Somatostatin Analogues for Neuroendocrine Tumour Diagnosis: The Benefits and Drawbacks of [ 64Cu]Cu-DOTA-TOC. Cancers (Basel) 2022; 14:1914. [PMID: 35454822 PMCID: PMC9027354 DOI: 10.3390/cancers14081914] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 04/07/2022] [Accepted: 04/08/2022] [Indexed: 02/04/2023] Open
Abstract
Neuroendocrine tumours (NETs) arise from secondary epithelial cell lines in the gastrointestinal or respiratory system organs. The rate of development of these tumours varies from an indolent to an aggressive course, typically being initially asymptomatic. The identification of these tumours is difficult, particularly because the primary tumour is often small and undetectable by conventional anatomical imaging. Consequently, diagnosis of NETs is complicated and has been a significant challenge until recently. In the last 30 years, the advent of novel nuclear medicine diagnostic procedures has led to a substantial increase in NET detection. Great varieties of exclusive single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals for detecting NETs are being applied successfully in clinical settings, including [111In]In-pentetreotide, [99mTc]Tc-HYNIC-TOC/TATE, [68Ga]Ga-DOTA-TATE, and [64Cu]Cu-DOTA-TOC/TATE. Among these tracers for functional imaging, PET radiopharmaceuticals are clearly and substantially superior to planar or SPECT imaging radiopharmaceuticals. The main advantages include higher resolution, better sensitivity and increased lesion-to-background uptake. An advantage of diagnosis with a radiopharmaceutical is the capacity of theranostics to provide concomitant diagnosis and treatment with particulate radionuclides, such as beta and alpha emitters including Lutetium-177 (177Lu) and Actinium-225 (225Ac). Due to these unique challenges involved with diagnosing NETs, various PET tracers have been developed. This review compares the clinical characteristics of radiolabelled somatostatin analogues for NET diagnosis, focusing on the most recently FDA-approved [64Cu]Cu-DOTA-TATE as a state-of-the art NET-PET/CT radiopharmaceutical.
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Affiliation(s)
- Nasim Vahidfar
- Department of Nuclear Medicine, Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran 1419733133, Iran; (N.V.); (S.F.); (M.A.); (Y.S.)
| | - Saeed Farzanehfar
- Department of Nuclear Medicine, Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran 1419733133, Iran; (N.V.); (S.F.); (M.A.); (Y.S.)
| | - Mehrshad Abbasi
- Department of Nuclear Medicine, Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran 1419733133, Iran; (N.V.); (S.F.); (M.A.); (Y.S.)
| | - Siroos Mirzaei
- Clinic Ottakring, Institute of Nuclear Medicine with PET-Center, 1220 Vienna, Austria;
| | - Ebrahim S. Delpassand
- RadioMedix, Inc., Houston, TX 77041, USA;
- Excel Diagnostics and Nuclear Oncology Center, Houston, TX 77042, USA
| | - Farzad Abbaspour
- Division of Nuclear Medicine, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON K1H 8L6, Canada;
| | - Yalda Salehi
- Department of Nuclear Medicine, Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran 1419733133, Iran; (N.V.); (S.F.); (M.A.); (Y.S.)
| | - Hans Jürgen Biersack
- Department of Nuclear Medicine, University Hospital Bonn, 53127 Bonn, Germany;
- Betaklinik Bonn, 53227 Bonn, Germany
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Galldiks N, Angenstein F, Werner JM, Bauer EK, Gutsche R, Fink GR, Langen KJ, Lohmann P. Use of advanced neuroimaging and artificial intelligence in meningiomas. Brain Pathol 2022; 32:e13015. [PMID: 35213083 PMCID: PMC8877736 DOI: 10.1111/bpa.13015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 06/09/2021] [Accepted: 08/02/2021] [Indexed: 01/04/2023] Open
Abstract
Anatomical cross‐sectional imaging methods such as contrast‐enhanced MRI and CT are the standard for the delineation, treatment planning, and follow‐up of patients with meningioma. Besides, advanced neuroimaging is increasingly used to non‐invasively provide detailed insights into the molecular and metabolic features of meningiomas. These techniques are usually based on MRI, e.g., perfusion‐weighted imaging, diffusion‐weighted imaging, MR spectroscopy, and positron emission tomography. Furthermore, artificial intelligence methods such as radiomics offer the potential to extract quantitative imaging features from routinely acquired anatomical MRI and CT scans and advanced imaging techniques. This allows the linking of imaging phenotypes to meningioma characteristics, e.g., the molecular‐genetic profile. Here, we review several diagnostic applications and future directions of these advanced neuroimaging techniques, including radiomics in preclinical models and patients with meningioma.
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Affiliation(s)
- Norbert Galldiks
- Department of Neurology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.,Institute of Neuroscience and Medicine (INM-3, -4), Research Center Juelich, Juelich, Germany.,Center for Integrated Oncology (CIO), Universities of Aachen, Cologne, Germany
| | - Frank Angenstein
- Functional Neuroimaging Group, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Magdeburg, Germany.,Leibniz Institute for Neurobiology (LIN), Magdeburg, Germany.,Medical Faculty, Otto von Guericke University, Magdeburg, Germany
| | - Jan-Michael Werner
- Department of Neurology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Elena K Bauer
- Department of Neurology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Robin Gutsche
- Institute of Neuroscience and Medicine (INM-3, -4), Research Center Juelich, Juelich, Germany
| | - Gereon R Fink
- Department of Neurology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.,Institute of Neuroscience and Medicine (INM-3, -4), Research Center Juelich, Juelich, Germany
| | - Karl-Josef Langen
- Institute of Neuroscience and Medicine (INM-3, -4), Research Center Juelich, Juelich, Germany.,Center for Integrated Oncology (CIO), Universities of Aachen, Cologne, Germany.,Department of Nuclear Medicine, University Hospital Aachen, Aachen, Germany
| | - Philipp Lohmann
- Institute of Neuroscience and Medicine (INM-3, -4), Research Center Juelich, Juelich, Germany.,Department of Stereotaxy and Functional Neurosurgery, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
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Loft M, Carlsen EA, Johnbeck CB, Jensen CV, Andersen FL, Langer SW, Oturai P, Knigge U, Kjaer A. Activity Dose Reduction in 64Cu-DOTATATE PET in Patients with Neuroendocrine Neoplasms: Impact on Image Quality and Lesion Detection Ability. Mol Imaging Biol 2022; 24:600-611. [PMID: 35167028 DOI: 10.1007/s11307-022-01706-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 01/12/2022] [Accepted: 01/20/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE Patients with neuroendocrine neoplasms (NEN) engage in lifelong follow-up with frequent somatostatin receptor PET, e.g. [64Cu]Cu-DOTATATE PET, and continued measures to reduce radiation exposures should be in pursued in accordance with the as-low-as-reasonably-achievable (ALARA) principle. We therefore aimed to determine the lowest achievable [64Cu]Cu-DOTATATE dose while maintaining image quality and lesion detection rate. PROCEDURES We included scans from 38 patients with NEN referred to routine [64Cu]Cu-DOTATATE PET/CT. Using reconstruction of under-sampled PET list-mode data, we simulated [64Cu]Cu-DOTATATE activity dose-reduced PET equivalents with median [range] 142 MBq [127;157], 95 MBq [85;105], and 48 MBq [42;52], corresponding to 75% (PET75%), 50% (PET50%), and 25% (PET25%) of the full-dose 191 MBq [169;209] (PET100%). Three blinded readers independently assessed image quality (scores 1-5), lesion confidence (scores 0-2), and counted lesions grouped by organs and regions. Number of lesions, proportions of patients with diagnostic image quality (reader-median image quality ≥ 4), diagnostic lesion confidence (reader-median lesion confidence ≥ 1), and per-patient sensitivities and specificities for organ-specific disease on PET75-25% were compared with PET100%. RESULTS The median [64Cu]Cu-DOTATATE activity dose could be reduced from 191 to 142 MBq without decline in diagnostic image quality (P = 0.62), diagnostic lesion confidence (P = 1.0), or number of lesions detected in major organs or regions (P = 0.19-0.71). Sensitivity and specificity for detection of liver disease were 100% (26/26 patients) and 100% (12/12), respectively, for both PET75% and PET50%. Overall sensitivity for detection of NEN was 100% (26/26) for both PET75% and PET50%, and overall specificities were 92% (11/12) and 100% (12/12) for PET75 and PET50, respectively. Following dose-blinded post hoc review, the PET75% specificity was adjusted to 100% (12/12). CONCLUSIONS The [64Cu]Cu-DOTATATE activity dose can be reduced from 191 MBq to at least 142 MBq without losing image quality or lesion detection ability and further reduced to 95 MBq without loss of clinically relevant information.
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Affiliation(s)
- Mathias Loft
- Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Esben A Carlsen
- Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Camilla B Johnbeck
- Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Christoffer V Jensen
- Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Flemming L Andersen
- Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Seppo W Langer
- ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.,Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Peter Oturai
- Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Ulrich Knigge
- ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.,Departments of Clinical Endocrinology and Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. .,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
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Naik M, Al-Nahhas A, Khan SR. Treatment of Neuroendocrine Neoplasms with Radiolabeled Peptides-Where Are We Now. Cancers (Basel) 2022; 14:761. [PMID: 35159027 PMCID: PMC8833798 DOI: 10.3390/cancers14030761] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 01/20/2022] [Indexed: 02/04/2023] Open
Abstract
Peptide receptor radionuclide therapy (PRRT) has been one of the most successful and exciting examples of theranostics in nuclear medicine in recent decades and is now firmly embedded in many treatment algorithms for unresectable or metastatic neuroendocrine neoplasms (NENs) worldwide. It is widely considered to be an effective treatment for well- or moderately differentiated neoplasms, which express high levels of somatostatin receptors that can be selectively targeted. This review article outlines the scientific basis of PRRT in treatment of NENs and describes its discovery dating back to the early 1990s. Early treatments utilizing Indium-111, a γ-emitter, showed promise in reduction in tumor size and improvement in biochemistry, but were also met with high radiation doses and myelotoxic and nephrotoxic effects. Subsequently, stable conjugation of DOTA-peptides with β-emitting radionuclides, such as Yttrium-90 and Lutetium-177, served as a breakthrough for PRRT and studies highlighted their potential in eliciting progression-free survival and quality of life benefits. This article will also elaborate on the key trials which paved the way for its approval and will discuss therapeutic considerations, such as patient selection and administration technique, to optimize its use.
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Affiliation(s)
- Mitesh Naik
- Department of Imaging, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK;
| | | | - Sairah R. Khan
- Department of Imaging, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK;
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32
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Copper Isotopes in Theranostics. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00073-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Jeppesen TE, Simón M, Torp J, Knudsen LBS, Leth JM, Crestey F, Ploug M, Jørgensen JT, Madsen J, Herth MM, Kjaer A. Optimization and Evaluation of Al 18F Labeling Using a NOTA-or RESCA1-Conjugated AE105 Peptide Antagonist of uPAR. FRONTIERS IN NUCLEAR MEDICINE (LAUSANNE, SWITZERLAND) 2021; 1:799533. [PMID: 39355634 PMCID: PMC11440976 DOI: 10.3389/fnume.2021.799533] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 11/26/2021] [Indexed: 10/03/2024]
Abstract
Fluorine-18 displays almost ideal decay properties for positron emission tomography (PET) and allows for large scale production. As such, simplified methods to radiolabel peptides with fluorine-18 are highly warranted. Chelation of aluminium fluoride-18 toward specific peptides represents one method to achieve this. With the current methods, chelation of aluminium fluoride-18 can be achieved using NOTA-conjugated peptides. However, the heating to 90-100◦C that is required for this chelation approach may be deleterious to the targeting moiety of the probe. Recently, a new chelator, RESCA1, was developed allowing Al18F chelation at room temperature. Here, we optimize the labeling procedure enabling high chelation efficacy of fluoride-18 at 22◦C, even at full batch labeling. The optimized procedure was tested by Al18F-labeling of RESCA1-AE105-a uPAR targeting peptide. NOTA-AE105 was also labeled with Al18F, and the two peptides were compared head-to-head. [18F]AlF-NOTA-AE105 and [18F]AlF-RESCA1-AE105 could be produced in equal radiochemical yields (RCY), radiochemical purities (RCP) and molar activities. Additionally, the two peptides showed comparable binding affinity to uPAR and uptake in cells expressing the uPAR, when evaluated in vitro. Overall, we found that the performances of [18F]AlF-NOTA-AE105 and [18F]AlF-RESCA1-AE105 were grossly comparable, but importantly RESCA1 can be labeled with aluminium fluoride-18 at 22◦C. Consequently, this study showed that RESCA1 is superior to NOTA with respect to Al18F chelation of temperature sensitive molecules, such as thermolabile peptides and proteins as well as that full batch chelation of RESCA1 with fluoride-18 is possible.
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Affiliation(s)
- Troels E Jeppesen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Marina Simón
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Josephine Torp
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Line B S Knudsen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Julie Maja Leth
- Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark
- Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark
| | - François Crestey
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Michael Ploug
- Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark
- Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark
| | - Jesper T Jørgensen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Jacob Madsen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Matthias M Herth
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
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Refardt J, Hofland J, Wild D, Christ E. New Directions in Imaging Neuroendocrine Neoplasms. Curr Oncol Rep 2021; 23:143. [PMID: 34735669 PMCID: PMC8568754 DOI: 10.1007/s11912-021-01139-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/05/2021] [Indexed: 12/14/2022]
Abstract
Purpose of Review Accurate imaging is crucial for correct diagnosis, staging, and therapy of neuroendocrine neoplasms (NENs). The search for the optimal imaging technique has triggered rapid development in the field. This review aims at giving an overview on contemporary imaging methods and providing an outlook on current progresses. Recent Findings The discovery of molecular targets due to the overexpression of specific peptide hormone receptors on the NEN’s surface has triggered the development of multiple radionuclide imaging modalities. In addition to the established imaging technique of targeting somatostatin receptors, several alternative radioligands have been developed. Targeting the glucagon-like peptide-1 receptor by exendin-4 has a high sensitivity in localizing insulinomas. For dedifferentiated NENs, new molecular targets such as the C-X-C motif chemokine-receptor-4 have been evaluated. Other new targets involve the fibroblast activation protein and the cholecystokinin-2 receptors, where the ligand minigastrin opens new possibilities for the management of medullary thyroid carcinoma. Summary Molecular imaging is an emerging field that improves the management of NENs.
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Affiliation(s)
- Julie Refardt
- Department of Internal Medicine, Section of Endocrinology, ENETS Center of Excellence, Erasmus Medical Center, Rotterdam, the Netherlands.,ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.,Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland
| | - Johannes Hofland
- Department of Internal Medicine, Section of Endocrinology, ENETS Center of Excellence, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Damian Wild
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.,Division of Nuclear Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland
| | - Emanuel Christ
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland. .,Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
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Gaffney B, Lynn E, Dodd JD, Keane MP, Murphy DJ, McCarthy C. The utility of gallium-68 DOTATOC PET/CT in lymphangioleiomyomatosis. ERJ Open Res 2021; 7:00397-2021. [PMID: 34708113 PMCID: PMC8542959 DOI: 10.1183/23120541.00397-2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 07/20/2021] [Indexed: 11/05/2022] Open
Abstract
Somatostatin receptor functional imaging is of limited utility as an imaging biomarker in LAM, but other PET/CT modalities may be of use https://bit.ly/3l6BVZp.
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Affiliation(s)
- Brian Gaffney
- Dept of Respiratory Medicine, St Vincent's University Hospital, Dublin, Ireland.,Dept of Radiology, St Vincent's University Hospital, Dublin, Ireland
| | - Evelyn Lynn
- Dept of Respiratory Medicine, St Vincent's University Hospital, Dublin, Ireland
| | - Jonathan D Dodd
- Dept of Radiology, St Vincent's University Hospital, Dublin, Ireland.,School of Medicine, University College Dublin, Dublin, Ireland
| | - Michael P Keane
- Dept of Respiratory Medicine, St Vincent's University Hospital, Dublin, Ireland.,School of Medicine, University College Dublin, Dublin, Ireland
| | - David J Murphy
- Dept of Radiology, St Vincent's University Hospital, Dublin, Ireland.,School of Medicine, University College Dublin, Dublin, Ireland
| | - Cormac McCarthy
- Dept of Respiratory Medicine, St Vincent's University Hospital, Dublin, Ireland.,School of Medicine, University College Dublin, Dublin, Ireland
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Wehrend J, Silosky M, Xing F, Chin BB. Automated liver lesion detection in 68Ga DOTATATE PET/CT using a deep fully convolutional neural network. EJNMMI Res 2021; 11:98. [PMID: 34601660 PMCID: PMC8487415 DOI: 10.1186/s13550-021-00839-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 09/12/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Gastroenteropancreatic neuroendocrine tumors most commonly metastasize to the liver; however, high normal background 68Ga-DOTATATE activity and high image noise make metastatic lesions difficult to detect. The purpose of this study is to develop a rapid, automated and highly specific method to identify 68Ga-DOTATATE PET/CT hepatic lesions using a 2D U-Net convolutional neural network. METHODS A retrospective study of 68Ga-DOTATATE PET/CT patient studies (n = 125; 57 with 68Ga-DOTATATE hepatic lesions and 68 without) was evaluated. The dataset was randomly divided into 75 studies for the training set (36 abnormal, 39 normal), 25 for the validation set (11 abnormal, 14 normal) and 25 for the testing set (11 abnormal, 14 normal). Hepatic lesions were physician annotated using a modified PERCIST threshold, and boundary definition by gradient edge detection. The 2D U-Net was trained independently five times for 100,000 iterations using a linear combination of binary cross-entropy and dice losses with a stochastic gradient descent algorithm. Performance metrics included: positive predictive value (PPV), sensitivity, F1 score and area under the precision-recall curve (PR-AUC). Five different pixel area thresholds were used to filter noisy predictions. RESULTS A total of 233 lesions were annotated with each abnormal study containing a mean of 4 ± 2.75 lesions. A pixel filter of 20 produced the highest mean PPV 0.94 ± 0.01. A pixel filter of 5 produced the highest mean sensitivity 0.74 ± 0.02. The highest mean F1 score 0.79 ± 0.01 was produced with a 20 pixel filter. The highest mean PR-AUC 0.73 ± 0.03 was produced with a 15 pixel filter. CONCLUSION Deep neural networks can automatically detect hepatic lesions in 68Ga-DOTATATE PET. Ongoing improvements in data annotation methods, increasing sample sizes and training methods are anticipated to further improve detection performance.
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Affiliation(s)
- Jonathan Wehrend
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, University of Colorado School of Medicine Anschutz Medical Campus, 12401 East 17th Avenue, Mail Stop L954A, Aurora, CO, 80045, USA
| | - Michael Silosky
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, University of Colorado School of Medicine Anschutz Medical Campus, 12401 East 17th Avenue, Mail Stop L954A, Aurora, CO, 80045, USA
| | - Fuyong Xing
- Department of Biostatistics and Informatics Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Bennett B Chin
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, University of Colorado School of Medicine Anschutz Medical Campus, 12401 East 17th Avenue, Mail Stop L954A, Aurora, CO, 80045, USA.
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Rossi RE, Elvevi A, Citterio D, Coppa J, Invernizzi P, Mazzaferro V, Massironi S. Gastrinoma and Zollinger Ellison syndrome: A roadmap for the management between new and old therapies. World J Gastroenterol 2021; 27:5890-5907. [PMID: 34629807 PMCID: PMC8475006 DOI: 10.3748/wjg.v27.i35.5890] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/29/2021] [Accepted: 08/10/2021] [Indexed: 02/06/2023] Open
Abstract
Zollinger-Ellison syndrome (ZES) associated with pancreatic or duodenal gastrinoma is characterized by gastric acid hypersecretion, which typically leads to gastroesophageal reflux disease, recurrent peptic ulcers, and chronic diarrhea. As symptoms of ZES are nonspecific and overlap with other gastrointestinal disorders, the diagnosis is often delayed with an average time between the onset of symptoms and final diagnosis longer than 5 years. The critical step for the diagnosis of ZES is represented by the initial clinical suspicion. Hypergastrinemia is the hallmark of ZES; however, hypergastrinemia might recognize several causes, which should be ruled out in order to make a final diagnosis. Gastrin levels > 1000 pg/mL and a gastric pH below 2 are considered to be diagnostic for gastrinoma; some specific tests, including esophageal pH-recording and secretin test, might be useful in selected cases, although they are not widely available. Endoscopic ultrasound is very useful for the diagnosis and the local staging of the primary tumor in patients with ZES, particularly in the setting of multiple endocrine neoplasia type 1. Some controversies about the management of these tumors also exist. For the localized stage, the combination of proton pump inhibitory therapy, which usually resolves symptoms, and surgery, whenever feasible, with curative intent represents the hallmark of gastrinoma treatment. The high expression of somatostatin receptors in gastrinomas makes them highly responsive to somatostatin analogs, supporting their use as anti-proliferative agents in patients not amenable to surgical cure. Other medical options for advanced disease are super-imposable to other neuroendocrine neoplasms, and studies specifically focused on gastrinomas only are scant and often limited to case reports or small retrospective series. The multidisciplinary approach remains the cornerstone for the proper management of this composite disease. Herein, we reviewed available literature about gastrinoma-associated ZES with a specific focus on differential diagnosis, providing potential diagnostic and therapeutic algorithms.
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Affiliation(s)
- Roberta Elisa Rossi
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy
| | - Alessandra Elvevi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza 20033, Italy
| | - Davide Citterio
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
| | - Jorgelina Coppa
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza 20033, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20122, Italy
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza 20033, Italy
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Abstract
Consensus guidelines acknowledge the role of gallium Ga-68 (68Ga) 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic (DOTA) somatostatin receptor (SSTR) positron emission tomography/computed tomography (PET/CT) in management of neuroendocrine tumor (NET) patients. 68Ga-DOTA-SSTR PET/CT demonstrates superior performance to conventional imaging in initial detection, staging, detection of recurrent tumor, and detection of unknown primary in known metastatic disease. 68Ga-DOTA-SSTR PET/CT is low yield for NET detection in the setting of symptoms or elevated biomarkers when conventional imaging is negative, but may still guide management. The role of 68Ga-DOTA-SSTR PET/CT is not established in monitoring response to systemic therapy but may identify progression through detection of new metastases.
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Affiliation(s)
- Janet Pollard
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA.
| | - Parren McNeely
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | - Yusuf Menda
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA
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Krokos G, Pike LC, Cook GJR, Marsden PK. Standardisation of conventional and advanced iterative reconstruction methods for Gallium-68 multi-centre PET-CT trials. EJNMMI Phys 2021; 8:52. [PMID: 34273020 PMCID: PMC8286213 DOI: 10.1186/s40658-021-00400-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 07/05/2021] [Indexed: 11/16/2022] Open
Abstract
PURPOSE To assess the applicability of the Fluorine-18 performance specifications defined by EANM Research Ltd (EARL), in Gallium-68 multi-centre PET-CT trials using conventional (ordered subset expectation maximisation, OSEM) and advanced iterative reconstructions which include the systems' point spread function (PSF) and a Bayesian penalised likelihood algorithm (BPL) commercially known as Q.CLEAR. The possibility of standardising the two advanced reconstruction methods was examined. METHODS The NEMA image quality phantom was filled with Gallium-68 and scanned on a GE PET-CT system. PSF and BPL with varying post-reconstruction Gaussian filter width (2-6.4 mm) and penalisation factor (200-1200), respectively, were applied. The average peak-to-valley ratio from six profiles across each sphere was estimated to inspect any edge artefacts. Image noise was assessed using background variability and image roughness. Six GE and Siemens PET-CT scanners provided Gallium-68 images of the NEMA phantom using both conventional and advanced reconstructions from which the maximum, mean and peak recoveries were drawn. Fourteen patients underwent 68Ga-PSMA PET-CT imaging. BPL (200-1200) reconstructions of the data were compared against PSF smoothed with a 6.4-mm Gaussian filter. RESULTS A Gaussian filter width of approximately 6 mm for PSF and a penalisation factor of 800 for BPL were needed to suppress the edge artefacts. In addition, those reconstructions provided the closest agreement between the two advanced iterative reconstructions and low noise levels with the background variability and the image roughness being lower than 7.5% and 11.5%, respectively. The recoveries for all methods generally performed at the lower limits of the EARL specifications, especially for the 13- and 10-mm spheres for which up to 27% (conventional) and 41% (advanced reconstructions) lower limits are suggested. The lesion standardised uptake values from the clinical data were significantly different between BPL and PSF smoothed with a Gaussian filter of 6.4 mm wide for all penalisation factors except for 800 and 1000. CONCLUSION It is possible to standardise the advanced reconstruction methods with the reconstruction parameters being also sufficient for minimising the edge artefacts and noise in the images. For both conventional and advanced reconstructions, Gallium-68 specific recovery coefficient limits were required, especially for the smallest phantom spheres.
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Affiliation(s)
- Georgios Krokos
- Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
| | - Lucy C Pike
- Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK
| | - Gary J R Cook
- Department of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK
| | - Paul K Marsden
- Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK
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Baiomy A, Schellingerhout D, Chapin BF, Weinberg JS, Raza SM, Macapinlac H, Ravizzini G. Rate of incidental central nervous system meningioma detected in patients undergoing 18F-fluciclovine PET/CT imaging for evaluation of prostate cancer. Nucl Med Commun 2021; 42:755-762. [PMID: 33741867 DOI: 10.1097/mnm.0000000000001389] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To evaluate the rate of incidental detection of central nervous system (CNS) meningioma in patients undergoing 18F-fluciclovine PET/computed tomography (CT) imaging for the evaluation of prostate cancer. METHODS The reports of 850 18F-fluciclovine PET/CT scans in 566 patients with pathologically proven prostate cancer performed from April 2017 to July 2019, were retrospectively reviewed for the presence of CNS meningioma. RESULTS A total of 14 patients (2.8%) (age range: 54-82 years old) had abnormal focal intracranial 18F-fluciclovine uptake, all extra-axial in location (SUVmax range: 3.2-19.3). Two cases out of 14 (0.35%) were diagnosed as metastatic lesions. Twelve out of the 14 patients, had 18F-fluciclovine PET/CT imaging findings suspicious for CNS meningioma, 2 of them received another diagnosis on further imaging, and only 10 cases (2%) had the diagnosis of meningioma according to follow-up MRI and 18F-fluciclovine PET/CT. CONCLUSION Focal 18F-fluciclovine avid intracranial lesions incidentally detected in patients undergoing PET/CT imaging for prostate cancer are most often CNS meningiomas.
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Affiliation(s)
| | | | | | | | | | - Homer Macapinlac
- Department of Nuclear Medicine The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Gregory Ravizzini
- Department of Nuclear Medicine The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Evaluation of 18F-AlF-NOTA-octreotide for imaging neuroendocrine neoplasms: comparison with 68Ga-DOTATATE PET/CT. EJNMMI Res 2021; 11:55. [PMID: 34106351 PMCID: PMC8190415 DOI: 10.1186/s13550-021-00797-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 05/28/2021] [Indexed: 12/18/2022] Open
Abstract
Objective To evaluate the diagnostic efficacy of 18F-AlF-NOTA-octreotide (18F-OC) PET/CT compared with that of 68Ga-DOTATATE PET/CT. Materials and methods Twenty patients (mean age: 52.65 years, range: 24–70 years) with biopsy-proven neuroendocrine neoplasms (NENs) were enrolled in this prospective study. We compared the biodistribution profiles in normal organs based on the maximum standard uptake value (SUVmax) and mean standard uptake value (SUVmean), and uptake in NEN lesions by measuring the SUVmax on 18F-OC and 68Ga-DOTATATE PET/CT images. The tumor-to-liver ratio (TLR) and tumor-to-spleen ratio were calculated by dividing the SUVmax of different tumor lesions by the SUVmean of the liver and spleen, respectively. The Wilcoxon signed-rank test was used to compare nonparametric data. Data were expressed as the median (interquartile range). Results In most organs, there were no significant differences in the biodistribution of 68Ga-DOTATATE and 18F-OC. 18F-OC had significantly lower uptake in the salivary glands and liver than 68Ga-DOTATATE. 18F-OC detected more lesions than 68Ga-DOTATATE. The uptake of 18F-OC in the tumors was higher in most patients, but the difference was not statistically significant relative to that of 68Ga-DOTATATE. However, the TLRs of 18F-OC were higher in most patients, including for lesions in the liver (p = 0.02) and lymph nodes (p = 0.02). Conclusion Relative to 68Ga-DOTATATE, 18F-OC possesses favorable characteristics with similar image quality and satisfactory NEN lesion detection rates, especially in the liver due to its low background uptake. 18F-OC therefore offers a promising clinical alternative for 68Ga-DOTATATE. Supplementary Information The online version contains supplementary material available at 10.1186/s13550-021-00797-4.
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Boekestijn I, Azargoshasb S, Schilling C, Navab N, Rietbergen D, van Oosterom MN. PET- and SPECT-based navigation strategies to advance procedural accuracy in interventional radiology and image-guided surgery. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF RADIOPHARMACEUTICAL CHEMISTRY AND BIOLOGY 2021; 65:244-260. [PMID: 34105338 DOI: 10.23736/s1824-4785.21.03361-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
INTRODUCTION Nuclear medicine has a crucial role in interventional strategies where a combination between the increasing use of targeted radiotracers and intraprocedural detection modalities enable novel, but often complex, targeted procedures in both the fields of interventional radiology and surgery. 3D navigation approaches could assist the interventional radiologist or surgeon in such complex procedures. EVIDENCE ACQUISITION This review aimed to provide a comprehensive overview of the current application of computer-assisted navigation strategies based on nuclear imaging to assist in interventional radiology and image-guided surgery. This work starts with a brief overview of the typical navigation workflow from a technical perspective, which is followed by the different clinical applications organized based on their anatomical organ of interest. EVIDENCE SYNTHESIS Although many studies have proven the feasibility of PET- and SPECT-based navigation strategies for various clinical applications in both interventional radiology and surgery, the strategies are spread widely in both navigation workflows and clinical indications, evaluated in small patient groups. Hence, no golden standard has yet been established. CONCLUSIONS Despite that the clinical outcome is yet to be determined in large patient cohorts, navigation seems to be a promising technology to translate nuclear medicine findings, provided by PET- and SPECT-based molecular imaging, to the intervention and operating room. Interventional Nuclear Medicine (iNM) has an exciting future to come using both PET- and SPECT-based navigation.
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Affiliation(s)
- Imke Boekestijn
- Department of Radiology, Section of Nuclear Medicine, Leiden University Medical Center, Leiden, the Netherlands.,Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Samaneh Azargoshasb
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Clare Schilling
- Head and Neck Academic Center, Department of Head and Neck Surgery, University College London Hospital, London, UK
| | - Nassir Navab
- Computer Aided Medical Procedures, Technical University of Munich, Munich, Germany.,Computer Aided Medical Procedures, Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA
| | - Daphne Rietbergen
- Department of Radiology, Section of Nuclear Medicine, Leiden University Medical Center, Leiden, the Netherlands.,Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Matthias N van Oosterom
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands - .,Department of Urology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands
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Jawlakh H, Velikyan I, Welin S, Sundin A. 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI are superior to 68 Ga-DOTATOC-PET/CT for neuroendocrine tumour imaging. J Neuroendocrinol 2021; 33:e12981. [PMID: 34046974 DOI: 10.1111/jne.12981] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/07/2021] [Accepted: 04/26/2021] [Indexed: 12/13/2022]
Abstract
The present study aimed to assess gadoxetate disodium contrast-enhanced (CE) positron emission tomography (PET)/magnetic resonance imaging (MRI) with 68 Ga-DOTATOC and 11 C-5-Hydroxy-tryptophan (11 C-5-HTP) in comparison with iodine CE 68 Ga-DOTATOC-PET/computed tomography (CT) for neuroendocrine tumour imaging. Detection rate and reader's confidence were evaluated for each separate image volume: CE-CT, CE-MRI including diffusion-weighted imaging, 68 Ga-DOTATOC-PET performed at PET/CT, 68 Ga-DOTATOC-PET performed at PET/MRI and 11 C-5-HTP-PET, and for the three combined hybrid examinations 68 Ga-DOTATOC-PET/MRI, 11 C-5-HTP-PET/MRI and 68 Ga-DOTATOC-PET/CT. In 11 patients, 255 lesions were depicted. 68 Ga-DOTATOC-PET performed at PET/MRI depicted 72.5%, 68 Ga-DOTATOC-PET performed at PET/CT depicted 62.7%, 11 C-5-HTP-PET depicted 68.2% and CE-CT depicted 53% of lesions. 68 Ga-DOTATOC-PET performed at PET/MRI (P < 0.001) and PET/CT (P = 0.02), 11 C-5-HTP-PET (P < 0.001) and MRI (P < 0.001) were superior to CT. 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI detected 92.5% and 92% of lesions, respectively, and both outperformed 68 Ga-DOTATOC-PET/CT (65%) (P < 0.001). For liver metastasis imaging, MRI alone was unsurpassed (P < 0.01) and 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI outperformed 68 Ga-DOTATOC-PET/CT (P < 0.001). For lymph node metastasis diagnosis, 68 Ga-DOTATOC-PET performed at PET/MRI and PET/CT and 11 C-5-HTP-PET detected 94%, 94% and 94% of lesions, respectively, and outperformed MRI and CE-CT alone (P < 0.001). For bone metastasis imaging, 68 Ga-DOTATOC-PET performed at PET/MRI and PET/CT and 11 C-5-HTP-PET performed equally well (P = 0.05) and better than MRI. Reader's confidence was better for 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI than for 68 Ga-DOTATOC-PET/CT. The tumour maximum standardised uptake value and tumour-to-liver ratio were both approximately twice as high as for 68 Ga-DOTATOC than for 11 C-5-HTP. 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI provided the highest detection rates and reader's confidence and were both superior to 68 Ga-DOTATOC-PET/CT, mainly because of the MRI component. The imaging contrast with 68 Ga-DOTATOC was superior to that of 11 C-5-HTP.
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Affiliation(s)
- Hiba Jawlakh
- Department of Surgical Sciences, Radiology and Molecular Imaging, Uppsala University, Uppsala, Sweden
| | - Irina Velikyan
- Department of Surgical Sciences, Radiology and Molecular Imaging, Uppsala University, Uppsala, Sweden
| | - Staffan Welin
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Anders Sundin
- Department of Surgical Sciences, Radiology and Molecular Imaging, Uppsala University, Uppsala, Sweden
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Holzgreve A, Albert NL, Galldiks N, Suchorska B. Use of PET Imaging in Neuro-Oncological Surgery. Cancers (Basel) 2021; 13:cancers13092093. [PMID: 33926002 PMCID: PMC8123649 DOI: 10.3390/cancers13092093] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Revised: 04/21/2021] [Accepted: 04/23/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary The use of positron emission tomography (PET) imaging in neuro-oncological surgery is an exciting field with thriving perspectives. Increasing evidence exists for amino acid-based PET to facilitate interpretation of imaging findings following therapeutic interventions in patients with glioma and brain metastases. In meningioma patients, radiolabeled somatostatin receptor ligands provide an improved tumor tissue visualization in lesions located in the vicinity of the skull base and differentiate between scar tissue and tumor recurrence. Moreover, they can be applied as an individual treatment option in recurrent atypical and anaplastic meningioma not eligible for further surgery and radiotherapy. With a focus on its clinical application, this review provides an overview of the emerging field of PET imaging in neuro-oncological surgery. Abstract This review provides an overview of current applications and perspectives of PET imaging in neuro-oncological surgery. The past and future of PET imaging in the management of patients with glioma and brain metastases are elucidated with an emphasis on amino acid tracers, such as O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET). The thematic scope includes surgical resection planning, prognostication, non-invasive prediction of molecular tumor characteristics, depiction of intratumoral heterogeneity, response assessment, differentiation between tumor progression and treatment-related changes, and emerging new tracers. Furthermore, the role of PET using specific somatostatin receptor ligands for the management of patients with meningioma is discussed. Further advances in neuro-oncological imaging can be expected from promising new techniques, such as hybrid PET/MR scanners and the implementation of artificial intelligence methods, such as radiomics.
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Affiliation(s)
- Adrien Holzgreve
- Department of Nuclear Medicine, University Hospital, LMU Munich, 81377 Munich, Germany; (A.H.); (N.L.A.)
| | - Nathalie L. Albert
- Department of Nuclear Medicine, University Hospital, LMU Munich, 81377 Munich, Germany; (A.H.); (N.L.A.)
| | - Norbert Galldiks
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany;
- Institute of Neuroscience and Medicine (INM-3), Research Center Juelich, 52425 Juelich, Germany
- Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne, and Duesseldorf, 50937 Cologne, Germany
| | - Bogdana Suchorska
- Department of Neurosurgery, Sana Kliniken Duisburg, 47055 Duisburg, Germany
- Correspondence: ; Tel.: +49-203-733-2401
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Effraimidis G, Knigge U, Rossing M, Oturai P, Rasmussen ÅK, Feldt-Rasmussen U. Multiple endocrine neoplasia type 1 (MEN-1) and neuroendocrine neoplasms (NENs). Semin Cancer Biol 2021; 79:141-162. [PMID: 33905872 DOI: 10.1016/j.semcancer.2021.04.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 01/03/2021] [Accepted: 04/16/2021] [Indexed: 12/14/2022]
Abstract
Neuroendocrine neoplasms (NENs) are relatively rare neoplasms with 6.4-times increasing age-adjusted annual incidence during the last four decades. NENs arise from neuroendocrine cells, which release hormones in response to neuronal stimuli and they are distributed into organs and tissues. The presentation and biological behaviour of the NENs are highly heterogeneous, depending on the organ. The increased incidence is mainly due to increased awareness and improved detection methods both in the majority of sporadic NENs (non-inherited), but also the inherited groups of neoplasms appearing in at least ten genetic syndromes. The most important one is multiple endocrine neoplasia type 1 (MEN-1), caused by mutations in the tumour suppressor gene MEN1. MEN-1 has been associated with different tumour manifestations of NENs e.g. pancreas, gastrointestinal tract, lungs, thymus and pituitary. Pancreatic NENs tend to be less aggressive when arising in the setting of MEN-1 compared to sporadic pancreatic NENs. There have been very important improvements over the past years in both genotyping, genetic counselling and family screening, introduction and validation of various relevant biomarkers, as well as newer imaging modalities. Alongside this development, both medical, surgical and radionuclide treatments have also advanced and improved morbidity, quality of life and mortality in many of these patients. Despite this progress, there is still space for improving insight into the genetic and epigenetic factors in relation to the biological mechanisms determining NENs as part of MEN-1. This review gives a comprehensive update of current evidence for co-occurrence, diagnosis and treatment of MEN-1 and neuroendocrine neoplasms and highlight the important progress now finding its way to international guidelines in order to improve the global management of these patients.
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Affiliation(s)
- Grigoris Effraimidis
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Ulrich Knigge
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Maria Rossing
- Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Peter Oturai
- Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Åse Krogh Rasmussen
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Ulla Feldt-Rasmussen
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark; Institute of Clinical Medicine, Faculty of Health Sciences, Copenhagen University, Denmark.
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Abstract
PET/computed tomography (CT) imaging increasingly is used in neuroendocrine neoplasms (NENs) for diagnosis, staging, monitoring, prognostication, and choosing treatment. Somatostatin PET analog tracers have added to the specificity by obtaining higher affinity to somatostatin receptors with 68Ga-labeled or 64Cu-labeled DOTA peptides compared with single-photon emission CT imaging isotopes. PET uptake correlates to tumor grade and is an essential part of theranostics with peptide receptor radionuclide treatment. This article focuses on the literature on head-to-head studies and meta-analyses of different combinations of peptide agonists and a few antagonists. Overall, the published data support the diagnostic capability of PET/CT imaging in NENs.
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Affiliation(s)
- Camilla Bardram Johnbeck
- Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen, Denmark; European Neuroendocrine Tumor Society Center of Excellence, Rigshospitalet, Copenhagen, Denmark
| | - Jann Mortensen
- Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen, Denmark; European Neuroendocrine Tumor Society Center of Excellence, Rigshospitalet, Copenhagen, Denmark; Medical Faculty, University of Copenhagen, Denmark.
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47
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Kato A, Nakamoto Y, Ishimori T, Hayakawa N, Ueda M, Temma T, Sano K, Shimizu Y, Saga T, Togashi K. Diagnostic performance of 68Ga-DOTATOC PET/CT in tumor-induced osteomalacia. Ann Nucl Med 2021; 35:397-405. [PMID: 33582980 DOI: 10.1007/s12149-021-01575-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 12/30/2020] [Indexed: 11/25/2022]
Abstract
OBJECTIVE Tumor-induced osteomalacia (TIO) is caused by typically small tumors that secrete fibroblast growth factor 23 (FGF23). As tumor resection is the only effective treatment for TIO, it is important to detect the culprit tumor. We aimed to assess the utility of 68Gallium-DOTA-D-Phe(1)-Tyr(3)-octreotide (68Ga-DOTATOC) PET/CT in TIO and the correlation between biochemical parameters and the PET/CT results. METHODS Thirty-five patients with clinically suspected TIO who had undergone 68Ga-DOTATOC PET/CT were retrospectively analyzed. 68Ga-DOTATOC PET/CT results were compared with biochemical parameters and the final diagnosis, including histopathology. RESULTS 68Ga-DOTATOC PET/CT detected focal uptake consistent with TIO in 21/35 patients, one of which was considered false positive. In 16 patients, the cause of osteomalacia was confirmed histologically as phosphaturic mesenchymal tumor (n = 15) or fibrous dysplasia (n = 1). The other four patients were judged clinically as true positive by subsequent MRI and the clinical course. Overall, the detection rate of 68Ga-DOTATOC PET/CT was 57% (20/35). Median tumor maximum standardized uptake value (SUVmax) was 6.9 (range 1.5-37.7). There was no significant difference in serum intact FGF23 level between DOTATOC-positive and DOTATOC-negative cases, and no significant correlation was observed between intact FGF23 level and tumor SUVmax. CONCLUSIONS 68Ga-DOTATOC PET/CT was clinically useful in detecting culprit tumors and subsequent patient management in TIO.
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Affiliation(s)
- Ayako Kato
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine Kyoto University, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Yuji Nakamoto
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine Kyoto University, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Takayoshi Ishimori
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine Kyoto University, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Nobuyuki Hayakawa
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine Kyoto University, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
- Department of Diagnostic Imaging, Kyoto City Hospital, Kyoto, Japan
| | - Masashi Ueda
- Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Takashi Temma
- Department of Biofunctional Analysis, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan
| | - Kohei Sano
- Laboratory of Biophysical Chemistry, Kobe Pharmaceutical University, Kobe, Japan
| | - Yoichi Shimizu
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine Kyoto University, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Tsuneo Saga
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine Kyoto University, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Kaori Togashi
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine Kyoto University, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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Loft M, Johnbeck CB, Carlsen EA, Johannesen HH, Oturai P, Langer SW, Knigge U, Kjaer A. Initial Experience with 64Cu-DOTATATE Digital PET of Patients with Neuroendocrine Neoplasms: Comparison with Analog PET. Diagnostics (Basel) 2021; 11:diagnostics11020350. [PMID: 33669838 PMCID: PMC7923227 DOI: 10.3390/diagnostics11020350] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 02/13/2021] [Accepted: 02/15/2021] [Indexed: 01/29/2023] Open
Abstract
The recent introduction of solid-state detectors in clinical positron emission tomography (PET) scanners has significantly improved image quality and spatial resolution and shortened acquisition time compared to conventional analog PET scanners. In an initial evaluation of the performance of our newly acquired Siemens Biograph Vision 600 PET/CT (digital PET/CT) scanner for 64Cu-DOTATATE imaging, we compared PET/CT acquisitions from patients with neuroendocrine neoplasms (NENs) grades 1 and 2 and stable disease on CT who were scanned on both our Siemens Biograph 128 mCT PET/CT (analog PET/CT) and digital PET/CT within 6 months as part of their routine clinical management. Five patients fulfilled the criteria and were included in the analysis. The digital PET acquisition time was less than 1/3 of the analog PET acquisition time (digital PET, mean (min:s): 08:20 (range, 07:59-09:45); analog PET, 25:28 (24:39-28:44), p < 0.001). All 44 lesions detected on the analog PET with corresponding structural correlates on the CT were also found on the digital PET performed 137 (107-176) days later. Our initial findings suggest that digital 64Cu-DOTATATE PET can successfully be performed in patients with NENs using an image acquisition time of only 1/3 of what is used for an analog 64Cu-DOTATATE PET.
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Affiliation(s)
- Mathias Loft
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark; (M.L.); (C.B.J.); (E.A.C.); (H.H.J.); (P.O.)
- ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, DK-2100 Copenhagen, Denmark; (S.W.L.); (U.K.)
| | - Camilla B. Johnbeck
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark; (M.L.); (C.B.J.); (E.A.C.); (H.H.J.); (P.O.)
- ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, DK-2100 Copenhagen, Denmark; (S.W.L.); (U.K.)
| | - Esben A. Carlsen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark; (M.L.); (C.B.J.); (E.A.C.); (H.H.J.); (P.O.)
- ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, DK-2100 Copenhagen, Denmark; (S.W.L.); (U.K.)
| | - Helle H. Johannesen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark; (M.L.); (C.B.J.); (E.A.C.); (H.H.J.); (P.O.)
- ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, DK-2100 Copenhagen, Denmark; (S.W.L.); (U.K.)
| | - Peter Oturai
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark; (M.L.); (C.B.J.); (E.A.C.); (H.H.J.); (P.O.)
- ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, DK-2100 Copenhagen, Denmark; (S.W.L.); (U.K.)
| | - Seppo W. Langer
- ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, DK-2100 Copenhagen, Denmark; (S.W.L.); (U.K.)
- Department of Clinical Oncology, Rigshospitalet, DK-2100 Copenhagen, Denmark
| | - Ulrich Knigge
- ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, DK-2100 Copenhagen, Denmark; (S.W.L.); (U.K.)
- Departments of Clinical Endocrinology and Surgical Gastroenterology, Rigshospitalet, DK-2100 Copenhagen, Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark; (M.L.); (C.B.J.); (E.A.C.); (H.H.J.); (P.O.)
- ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, DK-2100 Copenhagen, Denmark; (S.W.L.); (U.K.)
- Correspondence: ; Tel.: +45-3545-4216
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49
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Combined use of 177Lu-DOTATATE and metronomic capecitabine (Lu-X) in FDG-positive gastro-entero-pancreatic neuroendocrine tumors. Eur J Nucl Med Mol Imaging 2021; 48:3260-3267. [PMID: 33604690 DOI: 10.1007/s00259-021-05236-z] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 02/01/2021] [Indexed: 01/27/2023]
Abstract
PURPOSE FDG-positive neuroendocrine tumors (NETs) have a poorer prognosis and exhibit shorter response duration to peptide receptor radionuclide therapy (PRRT). The aim of this prospective phase II study was to evaluate the efficacy and toxicity of PRRT with 177Lu-DOTATATE associated with metronomic capecitabine as a radiosensitizer agent in patients with advanced progressive FDG-positive gastro-entero-pancreatic (GEP) NETs. PATIENTS AND METHODS Patients with advanced somatostatin receptor- and FDG-positive G1-G3 GEP-NETs (Ki67 < 55%) were treated with a cumulative activity of 27.5 GBq of 177Lu-DOTATATE divided in five cycles of 5.5 GBq each every 8 weeks. Capecitabine (1000-1500 mg daily) was administered orally in the inter-cycle period between 177Lu-DOTATATE treatments. Prior to commencing capecitabine, all patients were triaged with the dihydropyrimidine dehydrogenase (DPD) test. Only DPD-proficient individuals were enrolled. The primary objectives were disease control rate (DCR) and safety. Secondary aims included progression-free (PFS) and overall survival (OS). Treatment response was assessed per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). Toxicity was assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. RESULTS From August 2015 to December 2016, 37 subjects were consecutively enrolled. A total of 25 (68%) were affected by pancreatic neuroendocrine tumors (P-NETs), and 12 (32%) had gastrointestinal neuroendocrine tumors (GI-NETs). By grading (WHO 2010 classification), 12 patients (32%) had G1 (Ki67 ≤ 2%), 22 (59%) had G2 (3% < Ki67 ≤ 20%), and 3 patients (9%) had G3 (Ki67 > 20%) NETs. Grade 3 (G3) or 4 (G4) hematological toxicity occurred in 16.2% of patients. Other G3-G4 adverse events were diarrhea in 5.4% of cases and asthenia in 5.4%. No renal toxicity was observed for the duration of follow-up. In 37 patients, 33 were evaluable for response. Objective responses included partial response (PR) in 10 patients (30%) and stable disease (SD) in 18 patients (55%), with a DCR of 85%. The median follow-up was 38 months (range 4.6-51.1 months). The median PFS was 31.4 months (17.6-45.4), and mOS was not reached. CONCLUSIONS This study demonstrated that the combination of PRRT with 177Lu-DOTATATE and metronomic capecitabine is active and well tolerated in patients with aggressive FDG-positive G1-G3 GEP-NETs. These data constitute the basis for a randomized study of PPRT alone vs. PRRT plus metronomic capecitabine.
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50
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Roohi S, Rizvi SK, Naqvi SAR. 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Indigenously Developed Freeze Dried Cold Kit and Biological Response in In-Vitro and In-Vivo Models. Dose Response 2021; 19:1559325821990147. [PMID: 33628154 PMCID: PMC7883172 DOI: 10.1177/1559325821990147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 01/03/2021] [Accepted: 01/05/2021] [Indexed: 11/16/2022] Open
Abstract
Somatostatin receptors (SStR) based 177Lu-DOTATATE therapy is known as one of the highly effective neuroendocrine tumors (NETs) treatment strategy. Development of DOTATATE freeze-dried kit for imaging and therapy of SStR positive NETs is a prime goal in neuroendocrine cancer research. The present work describes the development of 177Lu-DOTATATE freeze dried cold kit for indigenous needs, through technology development fund (TDF) program offered by Higher Education Commission (HEC) Pakistan. The parameters for freeze dried kit production was optimized and tested the stored lyophilized cold kits for different time intervals after labeling with 177Lu radioisotope. The effect of ligand to radionuclide ratio, pH and reaction time at 90°C was recorded. Five times greater molar concentration of ligand, pH 5 and 30 min reaction time were the effective reaction conditions for maximum radiochemical yield. The radiolabeling yield at 1 day, 1-week and 4-week post storing period showed ∼100% radiochemical yield. The biodistribution study using rat model depicted the absence of non-targeted accumulation while glomerular filtration rate also explains the rapid renal washout. Cytotoxicity study showed quite favorable results for subjecting the radiopharmaceutical to clinical practice in Pakistan.
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Affiliation(s)
- Samina Roohi
- Isotope Production Division (IPD), Pakistan Institute of Nuclear Science and Technology (PINSTECH), Islamabad, Pakistan
| | - Shakera Khatoon Rizvi
- Isotope Production Division (IPD), Pakistan Institute of Nuclear Science and Technology (PINSTECH), Islamabad, Pakistan
| | - Syed Ali Raza Naqvi
- Department of Chemistry, Government College University, Faisalabad, Pakistan
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