Low kidney uptake of GLP-1R-targeting, beta cell-specific PET tracer, 18 F-labeled [Nle 14 ,Lys 40 ]exendin-4 analog, shows promise for clinical imaging.

Background: Several radiometal-labeled, exendin-based tracers that target glucagon-like peptide-1 receptors (GLP-1R) have been intensively explored for β cell imaging. The main obstacle has been the high uptake of tracer in the kidneys. This study aimed to develop a novel GLP1-R-specific tracer, with fluorine-18 attached to exendin-4, to label β cells for clinical imaging with PET (positron emission tomography). We hypothesized that this tracer would undergo reduced kidney uptake. ¹⁸ F-labeled [Nle ¹⁴ ,Lys ⁴⁰ ]exendin-4 analog ([ ¹⁸ F]exendin-4) was produced via Cu-catalyzed click chemistry. The biodistribution of [ ¹⁸ F]exendin-4 was assessed with ex vivo organ γ-counting and in vivo PET imaging. We also tested the in vivo stability of the radiotracer. The localization of ¹⁸ F radioactivity in rat and human pancreatic tissue sections was investigated with autoradiography. Receptor specificity was assessed with unlabeled exendin-3. Islet labeling was confirmed with immunohistochemistry. The doses of radiation in humans were estimated based on biodistribution results in rats.
Results: [ ¹⁸ F]exendin-4 was synthesized with high yield and high specific activity. Results showed specific, sustained [ ¹⁸ F]exendin-4 uptake in pancreatic islets. In contrast to previous studies that tested radiometal-labeled exendin-based tracers, we observed rapid renal clearance of [ ¹⁸ F]exendin-4.
Conclusions: [ ¹⁸ F]exendin-4 showed promise as a tracer for clinical imaging of pancreatic β cells, due to its high specific uptake in native β cells and its concomitant low kidney radioactivity uptake.