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 β-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 ([67/68Ga]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 [67Ga]GPBF in normal mice was evaluated. Finally, we carried out ex vivo autoradiography using mouse transplanted with amylin aggregates.

RESULTS

GPBF exhibited binding affinity for amylin aggregates in vitro. In addition, [67Ga]GPBF clearly labeled islet amyloids in in vitro autoradiography of a T2DM pancreatic section. In a biodistribution study using normal mice, [67Ga]GPBF 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 [67Ga]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.