In Vivo Imaging of Pancreatic Islet Grafts in Diabetes Treatment

Arifin, Dian R.; Bulte, Jeff W.M.

doi:10.3389/fendo.2021.640117

Cited by 13 publications

(47 citation statements)

References 65 publications

(131 reference statements)

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“…In a controlled, unilaterally nephrectomized mouse study, autoradiography showed the specific uptake of {Lys 40 [( 111In)DTPA]}exendin-3 in insulinexpressing cells, with the highest uptake in the pancreas and lungs followed by the kidneys (71). In another study, diabetic rats showed 111 In-[Lys 40 ]exendin-3 uptake in the pancreas (12).…”

Section: Visualization Of B Cells: Glucagon-like Peptide-1 Receptor-targeted Imagingmentioning

confidence: 98%

“…Biodistribution studies of [ 123 I] exendin-3 in rats harboring rat insulinoma cells (RINm5F) have shown rapid blood clearance and uptake of the radiotracer into the tumor and pancreas, which could be detected by SPECT. 111 In-labeled exendin-3, {Lys 40 [( 111In)DTPA]}exendin-3, was subsequently synthesized, given that the high sensitivity of 111 In-labeled tracers allowed for the administration of small amounts of tracer to prevent receptor saturation and adverse effects in SPECT (70). In a controlled, unilaterally nephrectomized mouse study, autoradiography showed the specific uptake of {Lys 40 [( 111In)DTPA]}exendin-3 in insulinexpressing cells, with the highest uptake in the pancreas and lungs followed by the kidneys (71).…”

Section: Visualization Of B Cells: Glucagon-like Peptide-1 Receptor-targeted Imagingmentioning

confidence: 99%

“…In addition, a moiety of ( 111 In) diethylenetriaminepentaacetic acid (DTPA) or tetraazacyclododecane tetraacetic acid (DOTA) via aminohexanoic acid linker (Ahx) has been introduced to obtain clearer SPECT images of the pancreas. In accordance with ( 125 I)BH reagents, partial modifications of exendin (9-39) at lysine residues and the N-terminus have been considered in the development of [ 111 In]DTPA-labeled derivatives (75). However, a crystal structure analysis suggested that modification of the lysine at position 27 would not improve the imaging of GLP-1R-positive tissues (75,76).…”

Section: Visualization Of B Cells: Glucagon-like Peptide-1 Receptor-targeted Imagingmentioning

confidence: 99%

“…However, a crystal structure analysis suggested that modification of the lysine at position 27 would not improve the imaging of GLP-1R-positive tissues (75,76). 111 In-[Lys 40 (Ahx-DTPA)NH2]exendin (9-39) probe showed reasonable affinity to GLP-1R in vitro, whereas a biodistribution study demonstrated low specific uptake without efficient retention or internalization of the probe, with lower accumulation in rat insulinoma INS-1 tumors and lower INS-1 tumor/pancreas contrast ratio compared with GLP-1R agonist-based counterparts (77). ( 111In)benzyl (Bn)DTPA-exendin (9-39) demonstrated higher affinity for GLP-1R compared with its parent compound, exendin (9-39), and clearly visualized INS-1 tumors in mice (75).…”

Section: Visualization Of B Cells: Glucagon-like Peptide-1 Receptor-targeted Imagingmentioning

confidence: 99%

“…In particular, radioisotope-labeled probes using exendin peptides [including glucagon-like peptide-1 (GLP-1) receptor agonist and antagonist] have been promising tools for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging. A number of these probes, including 111 indium-labeled exendin-4 derivative {[Lys 12 ( 111 In-BnDTPA-Ahx)]exendin-4}, have demonstrated the visualization of the mouse pancreas and its image analysis for BCM quantification and thereby have shown potential for clinical use (12)(13)(14)(15). This review focuses on the recent advances in non-invasive in vivo b-cell imaging and BCM evaluation for type 1 and type 2 diabetes mellitus, especially exendin-based GLP-1R-targeted nuclear medicine techniques.…”

Section: Introductionmentioning

confidence: 99%

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Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond

2021

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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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