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Nguyen T, Vennatt J, Downs L, Surabhi V, Stanietzky N. Advanced Imaging of Hepatocellular Carcinoma: A Review of Current and Novel Techniques. J Gastrointest Cancer 2024; 55:1469-1484. [PMID: 39158837 DOI: 10.1007/s12029-024-01094-8] [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] [Accepted: 07/16/2024] [Indexed: 08/20/2024]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary carcinoma arising from the liver. Although HCC can arise de novo, the vast majority of cases develop in the setting of chronic liver disease. Hepatocarcinogenesis follows a well-studied process during which chronic inflammation and cellular damage precipitate cellular and genetic aberrations, with subsequent propagation of precancerous and cancerous lesions. Surveillance of individuals at high risk of HCC, early diagnosis, and individualized treatment are keys to reducing the mortality associated with this disease. Radiological imaging plays a critical role in the diagnosis and management of these patients. HCC is a unique cancer in that it can be diagnosed with confidence by imaging that meets all radiologic criteria, obviating the risks associated with tissue sampling. This article discusses conventional and emerging imaging techniques for the evaluation of HCC.
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Affiliation(s)
- Trinh Nguyen
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Jaijo Vennatt
- Department of Diagnostic Radiology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA
| | - Lincoln Downs
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Venkateswar Surabhi
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Nir Stanietzky
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
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Larsen LI, López GP, Selwyn R, Carroll NJ. Microfluidic Fabrication of Silica Microspheres Infused with Positron Emission Tomography Imaging Agents. ACS APPLIED BIO MATERIALS 2023; 6:712-721. [PMID: 36633291 DOI: 10.1021/acsabm.2c00940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Selective internal radiation therapy (SIRT) is a treatment which delivers radioactive therapeutic microspheres via the hepatic artery to destroy tumorigenic tissue of the liver. However, the dose required varies significantly from patient to patient due to nuances in individual biology. Therefore, a positron emission tomography (PET) imaging surrogate, or radiotracer, is used to predict in vivo behavior of therapeutic Y-90 spheres. The ideal surrogate should closely resemble Y-90 microspheres in morphology for highest predictive accuracy. This work presents the fabrication of positron-emitting silica microspheres infused with PET radiotracers copper, fluorine, and gallium. A quick one-pot synthesis is used to create precursor sol, followed by droplet formation with flow-focusing microfluidics, and finally thermal treatment to yield 10-50 μm microspheres with narrow size distribution. Loading of the infused element is controllable in the sol synthesis, while the final sphere size is tunable based on microfluidic flow rates and device channel width. The system is then employed to make radioactive Ga-68 microspheres, which are tested for radioactivity and stability. The fabrication method can be completed within a few hours, depending on the desired microsphere quantity. A microfluidic system is applied to fabricate silica particles loaded with diverse elemental infusions, including radioactive Ga-68.
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Affiliation(s)
- Lewis I Larsen
- Department of Chemical and Biological Engineering, University of New Mexico, Albuquerque, New Mexico87131, United States.,Center for Micro-Engineered Materials, University of New Mexico, Albuquerque, New Mexico87131, United States
| | - Gabriel P López
- Department of Chemical and Biological Engineering, University of New Mexico, Albuquerque, New Mexico87131, United States.,Center for Micro-Engineered Materials, University of New Mexico, Albuquerque, New Mexico87131, United States
| | - Reed Selwyn
- Department of Radiology, University of New Mexico, Albuquerque, New Mexico87131, United States
| | - Nick J Carroll
- Department of Chemical and Biological Engineering, University of New Mexico, Albuquerque, New Mexico87131, United States.,Center for Micro-Engineered Materials, University of New Mexico, Albuquerque, New Mexico87131, United States
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Zucchetta P, Lacognata C, Girardi F, Spimpolo A, Crimì F, Cabrelle G, Zanon C, Boccagni P, Evangelista L, Cecchin D, Cillo U. [18F]FDG PET/MRI in the follow-up of hepatocellular carcinoma after liver transplantation. Nucl Med Commun 2022; 43:359-367. [PMID: 35019883 PMCID: PMC9897275 DOI: 10.1097/mnm.0000000000001518] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 11/24/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND There is limited evidence regarding the application of [18F] fluorodeoxyglucose (FDG)-PET/MRI in patients with a suspected clinical recurrence, who underwent liver transplantation for hepatocellular carcinoma (HCC). Therefore, we compared the accuracy of PET/MR and standard-of-care (SOC) imaging in these patients. METHODS We retrospectively reviewed 26 patients, whose liver were transplanted for HCC and were suspected of disease relapse based on biochemical analysis or SOC follow-up imaging, and carried out PET/MRI with diffusion-weighted imaging sequences on them. All patients underwent SOC imaging within the 2 months prior to the PET/MRI examination and had follow-up data for at least 12 months after. Reference standards were histopathology, clinical and imaging follow-up data. RESULTS Sensitivity, specificity, positive predictive value, negative predictive value and accuracy for PET/MRI were 100, 94, 91, 100 and 96%, whereas for SOC imaging were 80, 69, 61, 85 and 73%. The accuracy of PET/MRI was higher with respect to SOC imaging, although not significantly. CONCLUSIONS PET/MRI is useful for oncological surveillance of patients who have undergone liver transplantation for HCC, particularly in cases of allergy to contrast media, renal failure or persistently elevated alpha-fetoprotein levels, and with no identification of metastatic/relapsing foci at standard-of-care imaging.
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Affiliation(s)
- Pietro Zucchetta
- Department of Medicine – DIMED, Nuclear Medicine Unit, University of Padua
| | | | - Francesca Girardi
- Medicina Nucleare, Dipartimento di Diagnostica per Immagini, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste
| | | | | | | | | | - Patrizia Boccagni
- Department of Surgery, Hepatobiliary Surgery and Liver Transplant Center, Oncology and Gastroenterology (DISCOG), University of Padua, Padua, Italy
| | - Laura Evangelista
- Department of Medicine – DIMED, Nuclear Medicine Unit, University of Padua
| | - Diego Cecchin
- Department of Medicine – DIMED, Nuclear Medicine Unit, University of Padua
| | - Umberto Cillo
- Department of Surgery, Hepatobiliary Surgery and Liver Transplant Center, Oncology and Gastroenterology (DISCOG), University of Padua, Padua, Italy
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Gündoğan C, Ergül N, Çakır MS, Kılıçkesmez Ö, Gürsu RU, Aksoy T, Çermik TF. 68Ga-PSMA PET/CT Versus 18F-FDG PET/CT for Imaging of Hepatocellular Carcinoma. Mol Imaging Radionucl Ther 2021; 30:79-85. [PMID: 34082503 PMCID: PMC8185475 DOI: 10.4274/mirt.galenos.2021.92053] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objectives: This study aimed to compare the metabolic parameters obtained from 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and gallium-68 (68Ga)-prostate-specific membrane antigen (PSMA) PET/CT and investigate the relationship between serum alpha-fetoprotein and PET scan parameters in patients with hepatocellular carcinoma. Methods: Fourteen patients were recruited after dynamic magnetic resonance imaging (MRI) of the upper abdomen, and 18F-FDG and 68Ga-PSMA PET/CT imaging studies were conducted. Regions of interest (ROIs) were drawn from lesion-free liver tissue, abdominal aorta (A), and right medial gluteal muscle (G) for the background activity. Maximum standard uptake value (SUVmax) of these regions were compared with the SUVmax of primary tumor (T). Results: On visual assessment, five patients (36%) experienced low 18F-FDG uptake in the primary lesion, three patients (21%) experienced moderate uptake, and six patients (43%) experienced high uptake. However, only one patient (7%) showed low 68Ga-PSMA uptake, two patients (14%) showed moderate uptake, and 11 patients (79%) showed high uptake. Four patients with a low 18F-FDG uptake showed high 68Ga-PSMA uptake, while one patient exhibited low uptake with both 18F-FDG and 68Ga-PSMA. The number of lesions on 68Ga-PSMA PET/CT and MRI was significantly higher than 18F-FDG PET/CT (p=0.042 and 0.026, respectively). T/A and T/G values were significantly higher in 68Ga-PSMA than 18F-FDG (p=0.002 and 0.002, respectively). Conclusion: 68Ga-PSMA PET/CT is superior to 18F-FDG PET/CT in the staging of hepatocellular carcinoma. High 68Ga-PSMA uptake could be promising for PSMA-targeted radionuclide treatments.
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Affiliation(s)
- Cihan Gündoğan
- University of Health Sciences Turkey, Gazi Yaşargil Training and Research Hospital, Clinic of Nuclear Medicine, Diyarbakır, Turkey
| | - Nurhan Ergül
- University of Health Sciences Turkey, İstanbul Training and Research Hospital, Clinic of Nuclear Medicine, İstanbul, Turkey
| | - Mehmet Semih Çakır
- University of Health Sciences Turkey, İstanbul Training and Research Hospital, Clinic of Radiology, İstanbul, Turkey
| | - Özgür Kılıçkesmez
- University of Health Sciences Turkey, İstanbul Training and Research Hospital, Clinic of Radiology, İstanbul, Turkey
| | - Rıza Umar Gürsu
- University of Health Sciences Turkey, İstanbul Training and Research Hospital, Clinic of Medical Oncology, İstanbul, Turkey
| | - Tamer Aksoy
- University of Health Sciences Turkey, İstanbul Training and Research Hospital, Clinic of Nuclear Medicine, İstanbul, Turkey
| | - Tevfik Fikret Çermik
- University of Health Sciences Turkey, İstanbul Training and Research Hospital, Clinic of Nuclear Medicine, İstanbul, Turkey
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Osho A, Rich NE, Singal AG. Role of imaging in management of hepatocellular carcinoma: surveillance, diagnosis, and treatment response. ACTA ACUST UNITED AC 2020; 6. [PMID: 32944652 PMCID: PMC7494212 DOI: 10.20517/2394-5079.2020.42] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Imaging plays a notable role in hepatocellular carcinoma (HCC) surveillance, diagnosis, and treatment response assessment. Whereas HCC surveillance among at-risk patients, including those with cirrhosis, has traditionally been ultrasound-based, there are increasing data showing that this strategy is operator-dependent and has insufficient sensitivity when used alone. Several novel blood-based and imaging modalities are currently being evaluated to increase sensitivity for early HCC detection. Multi-phase computed tomography (CT) or contrast-enhanced magnetic resonance imaging (MRI) should be performed in patients with positive surveillance tests to confirm a diagnosis of HCC and perform cancer staging, as needed. HCC is a unique cancer in that most cases can be diagnosed radiographically without histological confirmation when demonstrating characteristic features such as arterial phase hyperenhancement and delayed phase washout. The Liver Imaging Reporting and Data System offers a standardized nomenclature for reporting CT or MRI liver findings among at-risk patients. Finally, cross-sectional imaging plays a critical role for assessing response to any HCC therapy as well as monitoring for HCC recurrence in those who achieve complete response.
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Affiliation(s)
- Azeez Osho
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390-8887, USA
| | - Nicole E Rich
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390-8887, USA
| | - Amit G Singal
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX 75390-8887, USA
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Lu RC, She B, Gao WT, Ji YH, Xu DD, Wang QS, Wang SB. Positron-emission tomography for hepatocellular carcinoma: Current status and future prospects. World J Gastroenterol 2019; 25:4682-4695. [PMID: 31528094 PMCID: PMC6718031 DOI: 10.3748/wjg.v25.i32.4682] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 06/30/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality worldwide. Various imaging modalities provide important information about HCC for its clinical management. Since positron-emission tomography (PET) or PET-computed tomography was introduced to the oncologic setting, it has played crucial roles in detecting, distinguishing, accurately staging, and evaluating local, residual, and recurrent HCC. PET imaging visualizes tissue metabolic information that is closely associated with treatment. Dynamic PET imaging and dual-tracer have emerged as complementary techniques that aid in various aspects of HCC diagnosis. The advent of new radiotracers and the development of immuno-PET and PET-magnetic resonance imaging have improved the ability to detect lesions and have made great progress in treatment surveillance. The current PET diagnostic capabilities for HCC and the supplementary techniques are reviewed herein.
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Affiliation(s)
- Ren-Cai Lu
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Bo She
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Wen-Tao Gao
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Yun-Hai Ji
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Dong-Dong Xu
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Quan-Shi Wang
- Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Shao-Bo Wang
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
- Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650093, Yunnan Province, China
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Huang YY, Poniger S, Tsai CL, Tochon-Danguy HJ, Ackermann U, Yen RF. Three-step two-pot automated production of NCA [ 18F]FDOPA with FlexLab module. Appl Radiat Isot 2019; 158:108871. [PMID: 32113705 DOI: 10.1016/j.apradiso.2019.108871] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 08/05/2019] [Accepted: 08/21/2019] [Indexed: 01/12/2023]
Abstract
Automated three-step two-pot production of no-carrier-added (NCA) [18F]FDOPA was first implemented in the iPHASE FlexLab module. Decay-corrected radiochemical yield (RCY) of [18F]FDOPA synthesized by this method was 10~14% (n = 7) with a synthesis time of ~110 min [18F]FDOPA was obtained in > 95% of radiochemical purity with a molar activity of ~431 GBq/μmol. With the method successfully implementing on the commercial FlexLab module and its built-in step-by-step activity monitoring, further processes optimization would be achieved.
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Affiliation(s)
- Ya-Yao Huang
- PET Center, Department of Nuclear Medicine, National Taiwan University Hospital, 7, Chung-Shan S. Road, Taipei, 100, Taiwan.
| | - Stan Poniger
- Department of Molecular Imaging and Therapy, Austin Health, 145 Studley Road, Heidelberg, Victoria, 3084, Australia; iPHASE Technologies, 3 Cypress Ave, Glen Waverley, Victoria, 3150, Australia
| | - Chia-Ling Tsai
- PET Center, Department of Nuclear Medicine, National Taiwan University Hospital, 7, Chung-Shan S. Road, Taipei, 100, Taiwan
| | - Henri J Tochon-Danguy
- Department of Molecular Imaging and Therapy, Austin Health, 145 Studley Road, Heidelberg, Victoria, 3084, Australia; iPHASE Technologies, 3 Cypress Ave, Glen Waverley, Victoria, 3150, Australia
| | - Uwe Ackermann
- Department of Molecular Imaging and Therapy, Austin Health, 145 Studley Road, Heidelberg, Victoria, 3084, Australia
| | - Ruoh-Fang Yen
- PET Center, Department of Nuclear Medicine, National Taiwan University Hospital, 7, Chung-Shan S. Road, Taipei, 100, Taiwan; Molecular Imaging Center, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei, 106, Taiwan
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Utility of [ 18F]FSPG PET to Image Hepatocellular Carcinoma: First Clinical Evaluation in a US Population. Mol Imaging Biol 2017; 18:924-934. [PMID: 27677886 DOI: 10.1007/s11307-016-1007-0] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE Non-invasive imaging is central to hepatocellular carcinoma (HCC) diagnosis; however, conventional modalities are limited by smaller tumors and other chronic diseases that are often present in patients with HCC, such as cirrhosis. This pilot study evaluated the feasibility of (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) positron emission tomography (PET)/X-ray computed tomography (CT) to image HCC. [18F]FSPG PET/CT was compared to standard-of-care (SOC) magnetic resonance imaging (MRI) and CT, and [11C]acetate PET/CT, commonly used in this setting. We report the largest cohort of HCC patients imaged to date with [18F]FSPG PET/CT and present the first comparison to [11C]acetate PET/CT and SOC imaging. This study represents the first in a US HCC population, which is distinguished by different underlying comorbidities than non-US populations. PROCEDURES xC- transporter RNA and protein levels were evaluated in HCC and matched liver samples from The Cancer Genome Atlas (n = 16) and a tissue microarray (n = 83). Eleven HCC patients who underwent prior MRI or CT scans were imaged by [18F]FSPG PET/CT, with seven patients also imaged with [11C]acetate PET/CT. RESULTS xC- transporter RNA and protein levels were elevated in HCC samples compared to background liver. Over 50 % of low-grade HCCs and ~70 % of high-grade tumors exceeded background liver protein expression. [18F]FSPG PET/CT demonstrated a detection rate of 75 %. [18F]FSPG PET/CT also identified an HCC devoid of typical MRI enhancement pattern. Patients scanned with [18F]FSPG and [11C]acetate PET/CT exhibited a 90 and 70 % detection rate, respectively. In dually positive tumors, [18F]FSPG accumulation consistently resulted in significantly greater tumor-to-liver background ratios compared with [11C]acetate PET/CT. CONCLUSIONS [18F]FSPG PET/CT is a promising modality for HCC imaging, and larger studies are warranted to examine [18F]FSPG PET/CT impact on diagnosis and management of HCC. [18F]FSPG PET/CT may also be useful for phenotyping HCC tumor metabolism as part of precision cancer medicine.
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Abstract
OBJECTIVE This article reviews recent developments in targeted radionuclide therapy (TRT) approaches directed to malignant liver lesions, bone metastases, neuroendocrine tumors, and castrate-resistant metastatic prostate cancer and discusses challenges and opportunities in this field. CONCLUSION TRT has been employed since the first radioiodine thyroid treatment almost 75 years ago. Progress in the understanding of the complex underlying biology of cancer and advances in radiochemistry science, multimodal imaging techniques including the concept of "see and treat" within the framework of theranostics, and universal traction with the notion of precision medicine have all contributed to a resurgence of TRT.
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Evaluation of two nucleophilic syntheses routes for the automated synthesis of 6-[ 18F]fluoro-l-DOPA. Nucl Med Biol 2016; 45:35-42. [PMID: 27886621 DOI: 10.1016/j.nucmedbio.2016.10.007] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Revised: 09/09/2016] [Accepted: 10/24/2016] [Indexed: 01/05/2023]
Abstract
Two different strategies for the nucleophilic radiosynthesis of [18F]F-DOPA were evaluated regarding their applicability for an automated routine production on an Ecker&Ziegler Modular-Lab Standard module. Initially, we evaluated a promising 5-step synthesis based on a chiral, cinchonidine-derived phase-transfer catalyst (cPTC) being described to give the product in high radiochemical yields (RCY), high specific activities (AS) and high enantiomeric excesses (ee). However, the radiosynthesis of [18F]F-DOPA based on this strategy showed to be highly complex, giving the intermediate products as well as the final product in insufficient yields for automatization. Furthermore, the automatization proved to be problematic due to incomplete radiochemical conversions and the formation of precipitates during the enantioselective reaction step. Furthermore, the required use of HI at 180°C during the last reaction step led to partial decomposition of lines and seals of the module which further counteracts an automatization. Further on, we evaluated a 3-step synthesis using the commercially available, enantiomerically pure precursor AB1336 for automatization. This synthesis approach gave much better results and [18F]F-DOPA could be produced fully automated within 114min in RCYs of 20±1%, ee of >96%, a radiochemical purity (RCP) of >98% and specific activities of up to 2.2GBq/μmol.
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Sotoudeh H, Sharma A, Fowler KJ, McConathy J, Dehdashti F. Clinical application of PET/MRI in oncology. J Magn Reson Imaging 2016; 44:265-76. [DOI: 10.1002/jmri.25161] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2014] [Accepted: 12/31/2015] [Indexed: 12/19/2022] Open
Affiliation(s)
- Houman Sotoudeh
- Edward Mallinckrodt Institute of Radiology; Washington University School of Medicine; St. Louis Missouri USA
- Washington University School of Medicine; St. Louis Missouri USA
| | - Akash Sharma
- Edward Mallinckrodt Institute of Radiology; Washington University School of Medicine; St. Louis Missouri USA
- Washington University School of Medicine; St. Louis Missouri USA
| | - Kathryn J. Fowler
- Edward Mallinckrodt Institute of Radiology; Washington University School of Medicine; St. Louis Missouri USA
- Washington University School of Medicine; St. Louis Missouri USA
- Edward Mallinckrodt Institute of Radiology; Alvin J. Siteman Cancer Center; Washington University School of Medicine; St. Louis Missouri USA
| | - Jonathan McConathy
- Edward Mallinckrodt Institute of Radiology; Washington University School of Medicine; St. Louis Missouri USA
- Washington University School of Medicine; St. Louis Missouri USA
- Edward Mallinckrodt Institute of Radiology; Alvin J. Siteman Cancer Center; Washington University School of Medicine; St. Louis Missouri USA
| | - Farrokh Dehdashti
- Edward Mallinckrodt Institute of Radiology; Washington University School of Medicine; St. Louis Missouri USA
- Washington University School of Medicine; St. Louis Missouri USA
- Edward Mallinckrodt Institute of Radiology; Alvin J. Siteman Cancer Center; Washington University School of Medicine; St. Louis Missouri USA
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Cillo U, Giuliani T, Polacco M, Herrero Manley LM, Crivellari G, Vitale A. Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation. World J Gastroenterol 2016; 22:232-252. [PMID: 26755873 PMCID: PMC4698488 DOI: 10.3748/wjg.v22.i1.232] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 08/14/2015] [Accepted: 11/09/2015] [Indexed: 02/06/2023] Open
Abstract
Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria, which are often inappropriate to express the tumor’s biological behavior and aggressiveness, offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT. Alpha-fetoprotein (AFP) and its progression as well as AFP-mRNA, AFP-L3%, des-γ-carboxyprothrombin, inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes. Several other markers for patient selection including functional imaging studies such as 18F-FDG-PET imaging, histological evaluation of tumor grade, tissue-specific biomarkers, and molecular signatures have been outlined in the literature. HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients. While AFP, its progression, and HCC response to pre-transplant therapy have already been used as a part of an integrated prognostic model for selecting patients, the utility of other markers in the transplant setting is still under investigation. This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.
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Brito AF, Abrantes AM, Ribeiro M, Oliveira R, Casalta-Lopes J, Gonçalves AC, Sarmento-Ribeiro AB, Tralhão JG, Botelho MF. Fluorine-18 Fluorodeoxyglucose Uptake in Hepatocellular Carcinoma: Correlation with Glucose Transporters and p53 Expression. J Clin Exp Hepatol 2015; 5:183-9. [PMID: 26628835 PMCID: PMC4632095 DOI: 10.1016/j.jceh.2015.05.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Accepted: 05/25/2015] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Hepatocellular Carcinoma (HCC) is one of most lethal cancers worldwide. The prognosis is very poor and therapeutic options are limited. The aim of this study was to determine the correlation of the [(18)F]FDG uptake profile of three HCC cell lines with p53 and glucose transporters (GLUTs) 1, 2, 3, 5 and 12 expression and with the glucose level present in the cell culture medium. METHODS Cell lines used are HepG2 (wp53), HuH7 (overexpress p53) and Hep3B2.1-7 (p53null). An immunocytochemical analysis was performed to evaluate p53 expression. Through uptake studies were analyzed the [(18)F]FDG uptake profiles of all cell lines under study. The expression of GLUTs were quantified by flow cytometry. The [(18)F]FDG uptake studies GLUTs expression analysis were performed on cells that grew in a high and low glucose medium in order to determine the effect of glucose concentration on GLUTs expression and on [(18)F]FDG uptake. RESULTS Immunocytochemical analysis confirmed the p53 expression profiles of all cell lines. It was found out that for all cell lines, [(18)F]FDG uptake is higher when cells grow in low glucose medium, however, the glucose level doesn't affect mostly the GLUTs expression. The Hep3B2.1-7 (p53null) is always the one that have higher [(18)F]FDG uptake. It was found that not always GLUT1 and GLUT3 are the most expressed by these cell lines. CONCLUSIONS Our results shown that the p53 expression influences [(18)F]FDG uptake. This suggests that [(18)F]FDG may be used in HCC diagnosis, and may even provide some information about the genetic profile of the tumor.
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Affiliation(s)
- Ana F. Brito
- Biophysics Unit, Faculty of Medicine of University of Coimbra, Coimbra, Portugal,Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine of University of Coimbra, Coimbra, Portugal,CNC.IBILI, University of Coimbra, Coimbra, Portugal,Address for correspondence: Ana F. Brito, Biophysics Unit, Faculty of Medicine of University of Coimbra, Pólo III – Pólo das Ciências da Saúde, Azinhaga de Santa Comba, Celas. 3000-548 Coimbra, Portugal. Tel.: +351 239480200; fax: +351 239480217.
| | - Ana M. Abrantes
- Biophysics Unit, Faculty of Medicine of University of Coimbra, Coimbra, Portugal,Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine of University of Coimbra, Coimbra, Portugal
| | - Marina Ribeiro
- Biophysics Unit, Faculty of Medicine of University of Coimbra, Coimbra, Portugal,Faculty of Sciences and Technology of University of Coimbra, Coimbra, Portugal
| | - Rui Oliveira
- Biophysics Unit, Faculty of Medicine of University of Coimbra, Coimbra, Portugal,Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine of University of Coimbra, Coimbra, Portugal,Anatomical Pathology Department, CHUC, Coimbra, Portugal
| | - João Casalta-Lopes
- Biophysics Unit, Faculty of Medicine of University of Coimbra, Coimbra, Portugal,Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine of University of Coimbra, Coimbra, Portugal
| | - Ana C. Gonçalves
- Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine of University of Coimbra, Coimbra, Portugal,CNC.IBILI, University of Coimbra, Coimbra, Portugal,Applied Molecular Biology and Hematology Group, Faculty of Medicine of University of Coimbra, Coimbra, Portugal
| | - Ana B. Sarmento-Ribeiro
- Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine of University of Coimbra, Coimbra, Portugal,CNC.IBILI, University of Coimbra, Coimbra, Portugal,Applied Molecular Biology and Hematology Group, Faculty of Medicine of University of Coimbra, Coimbra, Portugal
| | - José G. Tralhão
- Biophysics Unit, Faculty of Medicine of University of Coimbra, Coimbra, Portugal,Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine of University of Coimbra, Coimbra, Portugal,Surgical Department A, CHUC, Coimbra, Portugal
| | - Maria F. Botelho
- Biophysics Unit, Faculty of Medicine of University of Coimbra, Coimbra, Portugal,Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine of University of Coimbra, Coimbra, Portugal,CNC.IBILI, University of Coimbra, Coimbra, Portugal
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14
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Asman Y, Evenson AR, Even-Sapir E, Shibolet O. [18F]fludeoxyglucose positron emission tomography and computed tomography as a prognostic tool before liver transplantation, resection, and loco-ablative therapies for hepatocellular carcinoma. Liver Transpl 2015; 21:572-80. [PMID: 25644857 DOI: 10.1002/lt.24083] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2014] [Revised: 01/08/2015] [Accepted: 01/18/2015] [Indexed: 12/19/2022]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. Orthotopic liver transplantation (OLT) and resection are curative treatment options for well-selected patients with HCC, whereas loco-ablative therapy has been shown to prolong survival. Organ and treatment allocations for these patients are currently based on the number and size of tumors, as defined by the Milan criteria, and on functional capacity, and they are incorporated into the Barcelona Clinic Liver Cancer staging system and treatment strategy. Even though these staging criteria have markedly improved the outcomes of patients with HCC, they still lack accuracy in predicting the risk of tumor recurrence because they do not incorporate markers of tumor biology and behavior. Positron emission tomography (PET) and computed tomography (CT) with [(18) F]fludeoxyglucose ([(18) F]FDG) constitute an imaging modality for detecting tumor tissue that is metabolically active. Uptake of [(18) F]FDG is highly associated with tumor aggressiveness. In this review, we present the accumulating data on the use of [(18) F]FDG PET-CT as an in vivo biomarker and its predictive value in identifying patients at risk for HCC recurrence after liver transplantation, resection, or ablation. These data suggest that the introduction of [(18) F]FDG PET-CT into the imaging algorithm of patients planned for liver transplantation, resection, or ablation may improve outcomes.
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Affiliation(s)
- Yael Asman
- Liver Unit, Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel
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15
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Song L, Jin Z, Zhang W, Zhang Y. Gastric large cell neuroendocrine carcinoma with venous tumor thrombus: the value of PET/CT and contrast-enhanced computed tomography. Clin Imaging 2014; 39:325-8. [PMID: 25496669 DOI: 10.1016/j.clinimag.2014.09.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2014] [Revised: 08/28/2014] [Accepted: 09/05/2014] [Indexed: 02/07/2023]
Abstract
Venous involvement is commonly detected microscopically on gastric neuroendocrine carcinomas (NECs), but related imaging studies have been rarely documented. We report a rare case of gastric large cell NEC with tumor thrombi in gastric and splenic veins, elevated serum alpha fetoprotein, and multiple hepatic nodules. In this case, (18)F-fluorodeoxyglucose positron emission tomography combined with contrast-enhanced computed tomography provided valuable information on tumor staging.
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Affiliation(s)
- Le Song
- Department of Nuclear Medicine, Peking University Third Hospital, Beijing, China.
| | - Zhu Jin
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Weifang Zhang
- Department of Nuclear Medicine, Peking University Third Hospital, Beijing, China
| | - Yanyan Zhang
- Department of Nuclear Medicine, Peking University Third Hospital, Beijing, China
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16
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Bertagna F, Bertoli M, Bosio G, Biasiotto G, Sadeghi R, Giubbini R, Treglia G. Diagnostic role of radiolabelled choline PET or PET/CT in hepatocellular carcinoma: a systematic review and meta-analysis. Hepatol Int 2014. [PMID: 26202754 DOI: 10.1007/s12072-014-9566-0] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The role of fluorine-18-fluorodeoxygluose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in hepatocellular carcinoma (HCC) has not been firmly established yet and its sensitivity has been reported to be in the range of 40-60 %. Because of this relatively low sensitivity alternative tracers have been proposed. The aim of our review is to analyse the literature data on the diagnostic role of (18)F/(11)C-choline PET/CT in the evaluation of HCC. A comprehensive computer literature search of PubMed/MEDLINE, Embase and Scopus databases was conducted to find relevant published articles about the role of whole-body (18)F-choline or (11)C-choline PET or PET/CT in patients with HCC. Furthermore, a meta-analysis about the detection rate of this method in HCC was performed. Six articles were included in this systematic review and discussed. The meta-analysis of five out of six articles showed a DR of 84 % (95 % CI 79-89 %). The DR increased when poorly differentiated HCC was excluded from the analysis. Radiolabelled choline PET or PET/CT could be a valuable tool in detecting HCC and it is better than (18)F-FDG PET/CT, especially in well to moderately differentiated lesions; on the other hand, poorly differentiated and higher-stage HCC could be better evaluated with (18)F-FDG and dual tracer imaging should be considered and could be potentially useful to increase accuracy.
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Affiliation(s)
- Francesco Bertagna
- Nuclear Medicine, University of Brescia and Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123, Brescia, Italy.
| | - Mattia Bertoli
- Nuclear Medicine, University of Brescia and Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123, Brescia, Italy
| | - Giovanni Bosio
- Nuclear Medicine, University of Brescia and Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123, Brescia, Italy
| | - Giorgio Biasiotto
- Biomedical Technology Department, University of Brescia, Brescia, Italy
| | - Ramin Sadeghi
- Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Raffaele Giubbini
- Nuclear Medicine, University of Brescia and Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123, Brescia, Italy
| | - Giorgio Treglia
- Department of Nuclear Medicine and PET/CT Center, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
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17
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Pretze M, Wängler C, Wängler B. 6-[18F]fluoro-L-DOPA: a well-established neurotracer with expanding application spectrum and strongly improved radiosyntheses. BIOMED RESEARCH INTERNATIONAL 2014; 2014:674063. [PMID: 24987698 PMCID: PMC4058520 DOI: 10.1155/2014/674063] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2014] [Revised: 04/17/2014] [Accepted: 04/18/2014] [Indexed: 11/18/2022]
Abstract
For many years, the main application of [(18)F]F-DOPA has been the PET imaging of neuropsychiatric diseases, movement disorders, and brain malignancies. Recent findings however point to very favorable results of this tracer for the imaging of other malignant diseases such as neuroendocrine tumors, pheochromocytoma, and pancreatic adenocarcinoma expanding its application spectrum. With the application of this tracer in neuroendocrine tumor imaging, improved radiosyntheses have been developed. Among these, the no-carrier-added nucleophilic introduction of fluorine-18, especially, has gained increasing attention as it gives [(18)F]F-DOPA in higher specific activities and shorter reaction times by less intricate synthesis protocols. The nucleophilic syntheses which were developed recently are able to provide [(18)F]F-DOPA by automated syntheses in very high specific activities, radiochemical yields, and enantiomeric purities. This review summarizes the developments in the field of [(18)F]F-DOPA syntheses using electrophilic synthesis pathways as well as recent developments of nucleophilic syntheses of [(18)F]F-DOPA and compares the different synthesis strategies regarding the accessibility and applicability of the products for human in vivo PET tumor imaging.
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Affiliation(s)
- M. Pretze
- Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
| | - C. Wängler
- Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, 68167 Mannheim, Germany
| | - B. Wängler
- Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
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18
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Noij DP, Boerhout EJ, Pieters-van den Bos IC, Comans EF, Oprea-Lager D, Reinhard R, Hoekstra OS, de Bree R, de Graaf P, Castelijns JA. Whole-body-MR imaging including DWIBS in the work-up of patients with head and neck squamous cell carcinoma: a feasibility study. Eur J Radiol 2014; 83:1144-1151. [PMID: 24768188 DOI: 10.1016/j.ejrad.2014.03.019] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2013] [Revised: 03/17/2014] [Accepted: 03/21/2014] [Indexed: 12/20/2022]
Abstract
OBJECTIVES To assess the feasibility of whole-body magnetic resonance imaging (WB-MRI) including diffusion-weighted whole-body imaging with background-body-signal-suppression (DWIBS) for the evaluation of distant malignancies in head and neck squamous cell carcinoma (HNSCC); and to compare WB-MRI findings with (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) and chest-CT. METHODS Thirty-three patients with high risk for metastatic spread (26 males; range 48-79 years, mean age 63 ± 7.9 years (mean ± standard deviation) years) were prospectively included with a follow-up of six months. WB-MRI protocol included short-TI inversion recovery and T1-weighted sequences in the coronal plane and half-fourier acquisition single-shot turbo spin-echo T2 and contrast-enhanced-T1-weighted sequences in the axial plane. Axial DWIBS was reformatted in the coronal plane. Interobserver variability was assessed using weighted kappa and the proportion specific agreement (PA). RESULTS Two second primary tumors and one metastasis were detected on WB-MRI. WB-MRI yielded seven clinically indeterminate lesions which did not progress at follow-up. The metastasis and one second primary tumor were found when combining (18)F-FDG-PET/CT and chest-CT findings. Interobserver variability for WB-MRI was κ=0.91 with PA ranging from 0.82 to 1.00. For (18)F-FDG-PET/CT κ could not be calculated due to a constant variable in the table and PA ranged from 0.40 to 0.99. CONCLUSIONS Our WB-MRI protocol with DWIBS is feasible in the work-up of HNSCC patients for detection and characterization of distant pathology. WB-MRI can be complementary to (18)F-FDG-PET/CT, especially in the detection of non (18)F-FDG avid second primary tumors.
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Affiliation(s)
- Daniel P Noij
- Department of Radiology & Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands(1).
| | - Els J Boerhout
- Department of Radiology & Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands(1).
| | - Indra C Pieters-van den Bos
- Department of Radiology & Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands(1).
| | - Emile F Comans
- Department of Radiology & Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands(1).
| | - Daniela Oprea-Lager
- Department of Radiology & Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands(1).
| | - Rinze Reinhard
- Department of Radiology & Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands(1).
| | - Otto S Hoekstra
- Department of Radiology & Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands(1).
| | - Remco de Bree
- Department Otolaryngology/Head and Neck Surgery, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands(2).
| | - Pim de Graaf
- Department of Radiology & Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands(1).
| | - Jonas A Castelijns
- Department of Radiology & Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands(1).
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19
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Jadvar H, Colletti PM. Competitive advantage of PET/MRI. Eur J Radiol 2013; 83:84-94. [PMID: 23791129 DOI: 10.1016/j.ejrad.2013.05.028] [Citation(s) in RCA: 118] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2013] [Revised: 05/20/2013] [Accepted: 05/20/2013] [Indexed: 02/08/2023]
Abstract
Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved.
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Affiliation(s)
- Hossein Jadvar
- Division of Nuclear Medicine, Department of Radiology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.
| | - Patrick M Colletti
- Division of Nuclear Medicine, Department of Radiology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA
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20
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Freeman LM, Blaufox MD. Letter from the Editors: low-sensitivity FDG-PET studies. Semin Nucl Med 2012; 42:219-20. [PMID: 22681670 DOI: 10.1053/j.semnuclmed.2012.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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