Novel radiogallium-labeled pyridyl benzofuran derivative for detection of amylin aggregates in pancreas

Introduction: The deposition of islet amyloid composed of amylin aggregates is related to p-cell mass dysfunction in type 2 diabetes mellitus (T2DM), and it may be involved in the development and progression of T2DM. In this study, we newly designed, synthesized, and evaluated a radiogallium-labeled pyridyl benzofuran derivative ([Ga-67(/)68]GPBF) as an amylin imaging probe. Methods: An in vitro competitive inhibition assay was performed to determine the binding affinity for amylin aggregates. An in vitro autoradiographic study was carried out using pancreatic sections from a T2DM patient. A biodistribution of [Ga-67]GPBF in normal mice was evaluated. Finally, we carried out ex vivo autoradiography using mouse transplanted with amylin aggregates. Results: GPMFexhibited binding affinity for amylin aggregates in vitro. In addition, [Ga-67]GPBF dearly labeled islet amyloids in in vitro autoradiography of a T2DM pancreatic section. In a biodistribution study using normal mice, [Ga-67]GPEIF showed initial uptake into the pancreas, but non-specific accumulation in the liver, spleen, and pancreas was also observed. Furthermore, an ex vivo autoradiogram demonstrated that [Ga-67]GPBF bound to amylin aggregates in the pancreas of the amylin aggregate-transplanted mice. Conclusions: These results provide useful insights into the development of radiogallium labeled probes that target amylin aggregates in the T2DM pancreas. (C) 2020 Elsevier Inc. All rights reserved.