Insulinoma imaging with glucagon-like peptide-1 receptor targeting probe F-FBEM-Cys-exendin-4.

Purpose: Glucagon-like peptide-1 receptor (GLP-1R) is a specific target for insulinomas imaging since it is overexpressed in the tumor. Exendin-4 exhibits high affinity for the GLP-1R. In this study, a novel F-labeled exendin-4 analog, F-FBEM-Cys-exendin-4, was synthesized and its potentials for GLP-1R imaging were also evaluated. Methods: F-FBEM was synthesized by coupling F-fluorobenzoic acid (F-FBA) with N-(2-aminoethyl) maleimide, and the reaction conditions were optimized. Cys-exendin-4 was then conjugated with F-FBEM to obtain F-FBEM-Cys-exendin-4. The GLP-1R targeting potential and pharmacokinetic profile of the tracer were analyzed in INS-1 insulinoma and MDA-MB-435 breast tumor model, respectively. Results: Under the optimal conditions, the yield of radiolabeled F-FBEM was 49.1 ± 2.0 % (based on F-FBA, non-decay corrected). The yield of F-FBEM-Cys-exendin-4 was 35.1 ± 2.6 % (based on the starting F-FBEM, non-decay corrected). The radiochemical purity of F-FBEM-Cys-exendin-4 is >95 %, and the specific activity was at least 35 GBq/μmol. The GLP-1R-positive INS-1 insulinoma xenograft was clearly visible with good contrast to background, whereas GLP-1R-negative MDA-MB435 breast tumor was barely visible. Low levels of radioactivity were also detected at pancreas and lungs due to few GLP-1R expressions. GLP-1R binding specificity was demonstrated by reduced INS-1 tumor uptake of the tracer after coinjection with an excess of unlabeled Cys-exendin-4 at 1 h postinjection. Conclusion: The thiol-reactive reagent, F-FBEM, was prepared with high yield and successfully conjugated to Cys-exendin-4. Favorable preclinical data showing specific and effective tumor targeting by F-FBEM-Cys-exendin-4 suggest that the tracer may be a potential probe for insulinomas imaging. [ABSTRACT FROM AUTHOR]