68Ga-labelled-exendin-4: New GLP1R targeting agents for imaging pancreatic β-cell and insulinoma.

Abstract

OBJECTIVE\nGlucagon-like peptide-1 receptor (GLP1R) specifically expressed on the surface of pancreatic β-cells and insulinoma, is a potential biomarker for imaging β-cell mass (BCM). In this study, two new 68Ga-labelled GLP1R targeting agents were prepared and their biological properties for imaging BCM and insulinoma were evaluated.\n\n\nMETHODS\n[68Ga]Ga-HBED-CC-MAL-Cys39-exendin-4 ([68Ga]Ga-4) and its dimer ([68Ga]Ga-5) were synthesized from corresponding precursors. Cell uptake studies were evaluated in INS-1 cells. Biodistribution and microPET studies were performed in male normal Sprague-Dawley rats, diabetic rats and insulinoma xenograft NOD/SCID mice.\n\n\nRESULTS\n[68Ga]Ga-4 and [68Ga]Ga-5 were efficiently radiolabelled by a simple one-step reaction without purification leading to high radiochemical yields and radiochemical purities (both >95%, decay corrected, n\xa0=\xa06, molar activity 15\xa0GBq/μmol). They both showed excellent stability (~95%) in phosphate-buffered saline, pH\xa07.4, and in rat serum (~90%) for 2\xa0h. Biodistribution studies and small animal PET/CT imaging showed that [68Ga]Ga-4 displayed specific uptake in rat pancreas and mouse insulinoma, and a reduced uptake in the pancreas of diabetic rat was observed (~62% reduction). Notably, it exhibited a rapid time-to-peak pancreatic uptake (0.96\xa0±\xa00.19%ID/g in 15\xa0min) and fast clearance from the kidney (42% clearance in 30\xa0min). Results suggested a favorable in vivo kinetics for human imaging studies.\n\n\nCONCLUSIONS\n[68Ga]Ga-4 targeting GLP1R of pancreatic β-cells may be a potentially useful PET agent and a suitable candidate for further structural modification studies. This agent has demonstrated several advantages, rapid time-to-peak pancreatic uptake and faster clearance from the kidney, factors may enhance diagnosis of diabetes and insulinoma.