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Sipos D, Debreczeni-Máté Z, Ritter Z, Freihat O, Simon M, Kovács Á. Complex Diagnostic Challenges in Glioblastoma: The Role of 18F-FDOPA PET Imaging. Pharmaceuticals (Basel) 2024; 17:1215. [PMID: 39338377 PMCID: PMC11434841 DOI: 10.3390/ph17091215] [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: 08/13/2024] [Revised: 09/05/2024] [Accepted: 09/11/2024] [Indexed: 09/30/2024] Open
Abstract
Glioblastoma multiforme (GBM) remains one of the most aggressive and lethal forms of brain cancer, characterized by rapid proliferation and diffuse infiltration into the surrounding brain tissues. Despite advancements in therapeutic approaches, the prognosis for GBM patients is poor, with median survival times rarely exceeding 15 months post-diagnosis. An accurate diagnosis, treatment planning, and monitoring are crucial for improving patient outcomes. Core imaging modalities such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are indispensable in the initial diagnosis and ongoing management of GBM. Histopathology remains the gold standard for definitive diagnoses, guiding treatment by providing molecular and genetic insights into the tumor. Advanced imaging modalities, particularly positron emission tomography (PET), play a pivotal role in the management of GBM. Among these, 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-FDOPA) PET has emerged as a powerful tool due to its superior specificity and sensitivity in detecting GBM and monitoring treatment responses. This introduction provides a comprehensive overview of the multifaceted role of 18F-FDOPA PET in GBM, covering its diagnostic accuracy, potential as a biomarker, integration into clinical workflows, impact on patient outcomes, technological and methodological advancements, comparative effectiveness with other PET tracers, and its cost-effectiveness in clinical practice. Through these perspectives, we aim to underscore the significant contributions of 18F-FDOPA PET to the evolving landscape of GBM management and its potential to enhance both clinical and economic outcomes for patients afflicted with this formidable disease.
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Affiliation(s)
- David Sipos
- Department of Medical Imaging, Faculty of Health Sciences, University of Pécs, 7621 Pécs, Hungary
- Doctoral School of Health Sciences, Faculty of Health Sciences, University of Pécs, 7621 Pécs, Hungary
- Dr. József Baka Diagnostic, Radiation Oncology, Research and Teaching Center, “Moritz Kaposi” Teaching Hospital, Guba Sándor Street 40, 7400 Kaposvár, Hungary
| | - Zsanett Debreczeni-Máté
- Doctoral School of Health Sciences, Faculty of Health Sciences, University of Pécs, 7621 Pécs, Hungary
| | - Zsombor Ritter
- Department of Medical Imaging, Medical School, University of Pécs, 7621 Pécs, Hungary
| | - Omar Freihat
- Department of Public Health, College of Health Science, Abu Dhabi University, Abu Dhabi P.O. Box 59911, United Arab Emirates
| | - Mihály Simon
- Department of Oncoradiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
| | - Árpád Kovács
- Department of Medical Imaging, Faculty of Health Sciences, University of Pécs, 7621 Pécs, Hungary
- Doctoral School of Health Sciences, Faculty of Health Sciences, University of Pécs, 7621 Pécs, Hungary
- Department of Oncoradiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
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Lithovius V, Lahdenpohja S, Ibrahim H, Saarimäki-Vire J, Uusitalo L, Montaser H, Mikkola K, Yim CB, Keller T, Rajander J, Balboa D, Barsby T, Solin O, Nuutila P, Grönroos TJ, Otonkoski T. Non-invasive quantification of stem cell-derived islet graft size and composition. Diabetologia 2024; 67:1912-1929. [PMID: 38871836 PMCID: PMC11410899 DOI: 10.1007/s00125-024-06194-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 04/16/2024] [Indexed: 06/15/2024]
Abstract
AIMS/HYPOTHESIS Stem cell-derived islets (SC-islets) are being used as cell replacement therapy for insulin-dependent diabetes. Non-invasive long-term monitoring methods for SC-islet grafts, which are needed to detect misguided differentiation in vivo and to optimise their therapeutic effectiveness, are lacking. Positron emission tomography (PET) has been used to monitor transplanted primary islets. We therefore aimed to apply PET as a non-invasive monitoring method for SC-islet grafts. METHODS We implanted different doses of human SC-islets, SC-islets derived using an older protocol or a state-of-the-art protocol and SC-islets genetically rendered hyper- or hypoactive into mouse calf muscle to yield different kinds of grafts. We followed the grafts with PET using two tracers, glucagon-like peptide 1 receptor-binding [18F]F-dibenzocyclooctyne-exendin-4 ([18F]exendin) and the dopamine precursor 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA), for 5 months, followed by histological assessment of graft size and composition. Additionally, we implanted a kidney subcapsular cohort with different SC-islet doses to assess the connection between C-peptide and stem cell-derived beta cell (SC-beta cell) mass. RESULTS Small but pure and large but impure grafts were derived from SC-islets. PET imaging allowed detection of SC-islet grafts even <1 mm3 in size, [18F]exendin having a better detection rate than [18F]FDOPA (69% vs 44%, <1 mm3; 96% vs 85%, >1 mm3). Graft volume quantified with [18F]exendin (r2=0.91) and [18F]FDOPA (r2=0.86) strongly correlated with actual graft volume. [18F]exendin PET delineated large cystic structures and its uptake correlated with graft SC-beta cell proportion (r2=0.68). The performance of neither tracer was affected by SC-islet graft hyper- or hypoactivity. C-peptide measurements under fasted or glucose-stimulated conditions did not correlate with SC-islet graft volume or SC-beta cell mass, with C-peptide under hypoglycaemia having a weak correlation with SC-beta cell mass (r2=0.52). CONCLUSIONS/INTERPRETATION [18F]exendin and [18F]FDOPA PET enable non-invasive assessment of SC-islet graft size and aspects of graft composition. These methods could be leveraged for optimising SC-islet cell replacement therapy in diabetes.
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Affiliation(s)
- Väinö Lithovius
- Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
| | | | - Hazem Ibrahim
- Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Jonna Saarimäki-Vire
- Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | | | - Hossam Montaser
- Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Kirsi Mikkola
- Turku PET Centre, University of Turku, Turku, Finland
- Medicity Research Laboratories, University of Turku, Turku, Finland
| | - Cheng-Bin Yim
- Turku PET Centre, University of Turku, Turku, Finland
| | - Thomas Keller
- Turku PET Centre, University of Turku, Turku, Finland
| | - Johan Rajander
- Accelerator Laboratory, Turku PET Centre, Åbo Akademi University, Turku, Finland
| | - Diego Balboa
- Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Tom Barsby
- Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Olof Solin
- Turku PET Centre, University of Turku, Turku, Finland
- Accelerator Laboratory, Turku PET Centre, Åbo Akademi University, Turku, Finland
- Department of Chemistry, University of Turku, Turku, Finland
| | - Pirjo Nuutila
- Turku PET Centre, University of Turku, Turku, Finland
- Department of Endocrinology, Turku University Hospital, Turku, Finland
- The Wellbeing Services County of Southwest Finland, Turku, Finland
| | - Tove J Grönroos
- Turku PET Centre, University of Turku, Turku, Finland
- Medicity Research Laboratories, University of Turku, Turku, Finland
| | - Timo Otonkoski
- Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
- Children's Hospital, Helsinki University Hospital, Helsinki, Finland.
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Vyakaranam AR, Mahamed MM, Hellman P, Eriksson O, Espes D, Christoffersson G, Sundin A. Non-invasive imaging of sympathetic innervation of the pancreas in individuals with type 2 diabetes. Diabetologia 2024; 67:199-208. [PMID: 37935826 PMCID: PMC10709256 DOI: 10.1007/s00125-023-06039-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 07/31/2023] [Indexed: 11/09/2023]
Abstract
AIMS/HYPOTHESIS Compromised pancreatic sympathetic innervation has been suggested as a factor involved in both immune-mediated beta cell destruction and endocrine dysregulation of pancreatic islets. To further explore these intriguing findings, new techniques for in vivo assessment of pancreatic innervation are required. This is a retrospective study that aimed to investigate whether the noradrenaline (norepinephrine) analogue 11C-hydroxy ephedrine (11C-HED) could be used for quantitative positron emission tomography (PET) imaging of the sympathetic innervation of the human pancreas. METHODS In 25 individuals with type 2 diabetes and 64 individuals without diabetes, all of whom had previously undergone 11C-HED-PET/CT because of pheochromocytoma or paraganglioma (or suspicion thereof), the 11C-HED standardised uptake value (SUVmean), 11C-HED specific binding index (SBI), pancreatic functional volume (FV, in ml), functional neuronal volume (FNV, calculated as SUVmean × FV), specific binding index with functional volume (SBI FV, calculated as SBI × FV) and attenuation on CT (HU) were investigated in the entire pancreas, and additionally in six separate anatomical pancreatic regions. RESULTS Generally, 11C-HED uptake in the pancreas was high, with marked individual variation, suggesting variability in sympathetic innervation. Moreover, pancreatic CT attenuation (HU) (p<0.001), 11C-HED SBI (p=0.0049) and SBI FV (p=0.0142) were lower in individuals with type 2 diabetes than in individuals without diabetes, whereas 11C-HED SUVmean (p=0.15), FV (p=0.73) and FNV (p=0.30) were similar. CONCLUSIONS/INTERPRETATION We demonstrate the feasibility of using 11C-HED-PET for non-invasive assessment of pancreatic sympathetic innervation in humans. These findings warrant further prospective evaluation, especially in individuals with theoretical defects in pancreatic sympathetic innervation, such as those with type 1 diabetes.
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Affiliation(s)
- Achyut Ram Vyakaranam
- Department of Surgical Sciences, Section of Radiology & Molecular Imaging, Uppsala University, Uppsala, Sweden.
| | - Maryama M Mahamed
- Department of Surgical Sciences, Section of Radiology & Molecular Imaging, Uppsala University, Uppsala, Sweden
| | - Per Hellman
- Department of Surgical Sciences, Section of Radiology & Molecular Imaging, Uppsala University, Uppsala, Sweden
| | - Olof Eriksson
- Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
| | - Daniel Espes
- Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
- Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Gustaf Christoffersson
- Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
| | - Anders Sundin
- Department of Surgical Sciences, Section of Radiology & Molecular Imaging, Uppsala University, Uppsala, Sweden
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Joosten L, Boss M, Jansen T, Brom M, Buitinga M, Aarntzen E, Eriksson O, Johansson L, de Galan B, Gotthardt M. Molecular Imaging of Diabetes. Mol Imaging 2021. [DOI: 10.1016/b978-0-12-816386-3.00041-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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Murakami T, Fujimoto H, Inagaki N. Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond. Front Endocrinol (Lausanne) 2021; 12:714348. [PMID: 34248856 PMCID: PMC8270651 DOI: 10.3389/fendo.2021.714348] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 06/14/2021] [Indexed: 01/07/2023] Open
Abstract
Pancreatic beta (β)-cell dysfunction and reduced mass play a central role in the development and progression of diabetes mellitus. Conventional histological β-cell mass (BCM) analysis is invasive and limited to cross-sectional observations in a restricted sampling area. However, the non-invasive evaluation of BCM remains elusive, and practical in vivo and clinical techniques for β-cell-specific imaging are yet to be established. The lack of such techniques hampers a deeper understanding of the pathophysiological role of BCM in diabetes, the implementation of personalized BCM-based diabetes management, and the development of antidiabetic therapies targeting BCM preservation and restoration. Nuclear medical techniques have recently triggered a major leap in this field. In particular, radioisotope-labeled probes using exendin peptides that include glucagon-like peptide-1 receptor (GLP-1R) agonist and antagonist have been employed in positron emission tomography and single-photon emission computed tomography. These probes have demonstrated high specificity to β cells and provide clear images accurately showing uptake in the pancreas and transplanted islets in preclinical in vivo and clinical studies. One of these probes, 111indium-labeled exendin-4 derivative ([Lys12(111In-BnDTPA-Ahx)]exendin-4), has captured the longitudinal changes in BCM during the development and progression of diabetes and under antidiabetic therapies in various mouse models of type 1 and type 2 diabetes mellitus. GLP-1R-targeted imaging is therefore a promising tool for non-invasive BCM evaluation. This review focuses on recent advances in non-invasive in vivo β-cell imaging for BCM evaluation in the field of diabetes; in particular, the exendin-based GLP-1R-targeted nuclear medicine techniques.
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Affiliation(s)
- Takaaki Murakami
- Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hiroyuki Fujimoto
- Radioisotope Research Center, Agency of Health, Safety and Environment, Kyoto University, Kyoto, Japan
| | - Nobuya Inagaki
- Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan
- *Correspondence: Nobuya Inagaki,
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Wei W, Ehlerding EB, Lan X, Luo QY, Cai W. Molecular imaging of β-cells: diabetes and beyond. Adv Drug Deliv Rev 2019; 139:16-31. [PMID: 31378283 DOI: 10.1016/j.addr.2018.06.022] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Revised: 04/27/2018] [Accepted: 06/26/2018] [Indexed: 02/09/2023]
Abstract
Since diabetes is becoming a global epidemic, there is a great need to develop early β-cell specific diagnostic techniques for this disorder. There are two types of diabetes (i.e., type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM)). In T1DM, the destruction of pancreatic β-cells leads to reduced insulin production or even absolute insulin deficiency, which consequently results in hyperglycemia. Actually, a central issue in the pathophysiology of all types of diabetes is the relative reduction of β-cell mass (BCM) and/or impairment of the function of individual β-cells. In the past two decades, scientists have been trying to develop imaging techniques for noninvasive measurement of the viability and mass of pancreatic β-cells. Despite intense scientific efforts, only two tracers for positron emission tomography (PET) and one contrast agent for magnetic resonance (MR) imaging are currently under clinical evaluation. β-cell specific imaging probes may also allow us to precisely and specifically visualize transplanted β-cells and to improve transplantation outcomes, as transplantation of pancreatic islets has shown promise in treating T1DM. In addition, some of these probes can be applied to the preoperative detection of hidden insulinomas as well. In the present review, we primarily summarize potential tracers under development for imaging β-cells with a focus on tracers for PET, SPECT, MRI, and optical imaging. We will discuss the advantages and limitations of the various imaging probes and extend an outlook on future developments in the field.
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Alavi A, Werner TJ. Futility of attempts to detect and quantify beta cells by PET imaging in the pancreas: why it is time to abandon the approach. Diabetologia 2018; 61:2512-2515. [PMID: 29955934 DOI: 10.1007/s00125-018-4676-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 06/08/2018] [Indexed: 12/15/2022]
Abstract
In this commentary, we describe the limitations of positron emission tomography (PET) in visualising and characterising beta cell mass in the native pancreas in healthy individuals and those diagnosed with diabetes. Imaging with PET requires a large mass of targeted cells or other structures in the range of approximately 8-10 cm3. Since islets occupy only 1% of the pancreatic volume and are dispersed throughout the organ, it is our view that uptake of PET tracers, including [18F]fluoropropyl-(+)-dihydrotetrabenazine, in islets cannot be successfully detected by current imaging modalities. Therefore, we dispute the feasibility of PET imaging for the detection of loss of beta cells in the native pancreas in individuals with diabetes. However, we believe this novel approach can be successfully employed to visualise beta cell mass in individuals with hyperinsulinism and transplanted islets.
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Affiliation(s)
- Abass Alavi
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
| | - Thomas J Werner
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
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Willekens SMA, van der Kroon I, Bos D, Joosten L, Frielink C, Boerman OC, Brom M, Gotthardt M. Quantitative and longitudinal imaging of intramuscular transplanted islets of Langerhans with SPECT using [ 123 I]IBZM. Diabetes Obes Metab 2017; 19:604-608. [PMID: 27987245 DOI: 10.1111/dom.12857] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 11/30/2016] [Accepted: 12/12/2016] [Indexed: 11/30/2022]
Abstract
A non-invasive imaging method to monitor islet grafts could provide novel and improved insight into the fate of transplanted islets and, potentially, monitor the effect of therapeutic interventions. Therefore, such an imaging method could help improve long-term transplantation outcome. Here, we investigated the use of [ 123 I]IBZM for insulin positive graft volume quantification and longitudinal graft monitoring. SPECT images were acquired 6 weeks after islet transplantation in the calf muscle of rats. For longitudinal graft analysis, rats were monitored by SPECT for 10 weeks. After animals were euthanized, graft containing muscles were dissected for ex vivo analysis and insulin-positive graft volume determination. Six weeks after transplantation, a clear signal was observed in all grafts by SPECT imaging. Moreover, the intensity of the SPECT signal correlated linearly with insulin-positive graft volume, as determined histologically. Longitudinal graft follow-up showed a clear SPECT signal of the transplant from 3 until 10 weeks after transplantation. In this study, we demonstrate for the first time the successful application of a radiotracer, [ 123 I]IBZM, for non-invasive, in vivo graft volume quantification and longitudinal graft monitoring.
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Affiliation(s)
- Stefanie M A Willekens
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Inge van der Kroon
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Desirée Bos
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Lieke Joosten
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Cathelijne Frielink
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Otto C Boerman
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Maarten Brom
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Martin Gotthardt
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
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Kim D, Jun HS. In Vivo Imaging of Transplanted Pancreatic Islets. Front Endocrinol (Lausanne) 2017; 8:382. [PMID: 29403437 PMCID: PMC5786518 DOI: 10.3389/fendo.2017.00382] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 12/26/2017] [Indexed: 01/08/2023] Open
Abstract
The beta-cells in the islets of Langerhans in the pancreas secrete insulin and play an important role in glucose homeostasis. Diabetes, characterized by hyperglycemia, results from an absolute or a relative deficiency of the pancreatic beta-cell mass. Islet transplantation has been considered to be a useful therapeutic approach, but it is largely unsuccessful because most of the transplanted islets are lost in the early stage of transplantation. To evaluate the efficacy of intervention methods for the improvement of islet survival, monitoring of the functional islet mass is needed. Various techniques to image and track transplanted islets have been investigated to assess islets after transplantation. In this review, recent progresses in imaging methods to visualize islets are discussed.
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Affiliation(s)
- Donghee Kim
- Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, South Korea
| | - Hee-Sook Jun
- Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, South Korea
- College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, South Korea
- Gachon Medical Research Institute, Gil Hospital, Incheon, South Korea
- *Correspondence: Hee-Sook Jun,
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Li J, Karunananthan J, Pelham B, Kandeel F. Imaging pancreatic islet cells by positron emission tomography. World J Radiol 2016; 8:764-774. [PMID: 27721939 PMCID: PMC5039672 DOI: 10.4329/wjr.v8.i9.764] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Revised: 04/15/2016] [Accepted: 08/08/2016] [Indexed: 02/06/2023] Open
Abstract
It was estimated that every year more than 30000 persons in the United States - approximately 80 people per day - are diagnosed with type 1 diabetes (T1D). T1D is caused by autoimmune destruction of the pancreatic islet (β cells) cells. Islet transplantation has become a promising therapy option for T1D patients, while the lack of suitable tools is difficult to directly evaluate of the viability of the grafted islet over time. Positron emission tomography (PET) as an important non-invasive methodology providing high sensitivity and good resolution, is able to accurate detection of the disturbed biochemical processes and physiological abnormality in living organism. The successful PET imaging of islets would be able to localize the specific site where transplanted islets engraft in the liver, and to quantify the level of islets remain alive and functional over time. This information would be vital to establishing and evaluating the efficiency of pancreatic islet transplantation. Many novel imaging agents have been developed to improve the sensitivity and specificity of PET islet imaging. In this article, we summarize the latest developments in carbon-11, fluorine-18, copper-64, and gallium-68 labeled radioligands for the PET imaging of pancreatic islet cells.
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11
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Willekens SMA, van der Kroon I, Joosten L, Frielink C, Boerman OC, van den Broek SAMW, Brom M, Gotthardt M. SPECT of Transplanted Islets of Langerhans by Dopamine 2 Receptor Targeting in a Rat Model. Mol Pharm 2015; 13:85-91. [PMID: 26607139 DOI: 10.1021/acs.molpharmaceut.5b00518] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Pancreatic islet transplantation can be a more permanent treatment for type 1 diabetes compared to daily insulin administration. Quantitative and longitudinal noninvasive imaging of viable transplanted islets might help to further improve this novel therapy. Since islets express dopamine 2 (D2) receptors, they could be visualized by targeting this receptor. Therefore, the D2 receptor antagonist based tracer [(125/123)I][IBZM] was selected to visualize transplanted islets in a rat model. BZM was radioiodinated, and the labeling was optimized for position 3 of the aromatic ring. [(125)I]-3-IBZM was characterized in vitro using INS-1 cells and isolated islets. Subsequently, 1,000 islets were transplanted in the calf muscle of WAG/Rij rats and SPECT/CT images were acquired 6 weeks after transplantation. Finally, the graft containing muscle was dissected and analyzed immunohistochemically. Oxidative radioiodination resulted in 3 IBZM isomers with different receptor affinities. The use of 0.6 mg/mL chloramine-T hydrate resulted in high yield formation of predominantly [(125)I]-3-IBZM, the isomer harboring the highest receptor affinity. The tracer showed D2 receptor mediated binding to isolated islets in vitro. The transplant could be visualized by SPECT 6 weeks after transplantation. The transplants could be localized in the calf muscle and showed insulin and glucagon expression, indicating targeting of viable and functional islets in the transplant. Radioiodination was optimized to produce high yields of [(125)I]-3-IBZM, the isomer showing optimal D2R binding. Furthermore, [(123)I]IBZM specifically targets the D2 receptors on transplanted islets. In conclusion, this tracer shows potential for noninvasive in vivo detection of islets grafted in the muscle by D2 receptor targeting.
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Affiliation(s)
- Stefanie M A Willekens
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center , PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | - Inge van der Kroon
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center , PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | - Lieke Joosten
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center , PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | - Cathelijne Frielink
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center , PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | - Otto C Boerman
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center , PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | | | - Maarten Brom
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center , PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | - Martin Gotthardt
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center , PO Box 9101, 6500 HB Nijmegen, The Netherlands
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Barsanti C, Lenzarini F, Kusmic C. Diagnostic and prognostic utility of non-invasive imaging in diabetes management. World J Diabetes 2015; 6:792-806. [PMID: 26131322 PMCID: PMC4478576 DOI: 10.4239/wjd.v6.i6.792] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Revised: 12/23/2014] [Accepted: 04/14/2015] [Indexed: 02/05/2023] Open
Abstract
Medical imaging technologies are acquiring an increasing relevance to assist clinicians in diagnosis and to guide management and therapeutic treatment of patients, thanks to their non invasive and high resolution properties. Computed tomography, magnetic resonance imaging, and ultrasonography are the most used imaging modalities to provide detailed morphological reconstructions of tissues and organs. In addition, the use of contrast dyes or radionuclide-labeled tracers permits to get functional and quantitative information about tissue physiology and metabolism in normal and disease state. In recent years, the development of multimodal and hydrid imaging techniques is coming to be the new frontier of medical imaging for the possibility to overcome limitations of single modalities and to obtain physiological and pathophysiological measurements within an accurate anatomical framework. Moreover, the employment of molecular probes, such as ligands or antibodies, allows a selective in vivo targeting of biomolecules involved in specific cellular processes, so expanding the potentialities of imaging techniques for clinical and research applications. This review is aimed to give a survey of characteristics of main diagnostic non-invasive imaging techniques. Current clinical appliances and future perspectives of imaging in the diagnostic and prognostic assessment of diabetic complications affecting different organ systems will be particularly addressed.
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