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Glucagon-like peptide-1; Glucagon-like peptide-1 receptor; Exendin-4; Exendin(9-39); β-Cell imaging; Islet imaging; Molecular imaging; β-Cell mass; Diabetes
Introduction
However, it is difficult to identify islets ranging in size from 50–500 μm in diameter and scattered throughout the pancreas, which is surrounded by abdominal organs. To quantify β-cell mass non-invasively, appropriate probes that can specifically bind to pancreatic β-cells are required. There are previous reports using probes targeting the PRIMA-1 in β-cells, including sulfonylurea receptor 1 (SUR1) and monoamine transporter 2 (VMAT2) for positron emission tomography (PET) imaging [7]. However, ideal probes for accurate and non-invasive imaging for pancreatic β-cells have not yet been developed.
Glucagon-like peptide 1 (GLP-1) is the incretin peptide released from the intestine in response to nutrient ingestion to augment glucose-induced insulin secretion from pancreatic β-cells through binding to the GLP-1 receptor (GLP-1R) [8] and [9]. Since GLP-1R is expressed highly in islets, especially on β-cells in pancreas, the ligands of GLP-1R might well be ideal probes for pancreatic β-cell imaging. Because native GLP-1 is degraded rapidly by dipeptidyl peptidase-IV (DPP-IV) distributed throughout the body, DPP-IV-resistant agonistic or antagonistic ligands of GLP-1R [10] and [11] are preferable to GLP-1 for use as an imaging probe.