Preliminary evaluation of [F-18]AIF-NOTA-MAL-Cys(39)-exendin-4 in insulinoma with PET

摘要

Background: High expression of glucagon-like peptide-1 receptor (GLP-1R) in insulinoma supplies a potential drug target for tumor imaging. Exendin-4 can specifically bind to GLP-1R as an agonist and its analogs are extensively used in receptor imaging studies.Purpose: A new GLP-1R imaging agent, [F-18]AlF-NOTA-MAL-Cys(39)-exendin-4, was designed and prepared for insulinoma imaging.Methods: Cys(39)-exendin-4 was conjugated with NOTA-MAL, then the compound was radiolabeled with [F-18]AlF complex to obtained [F-18]AlF-NOTA-MAL-Cys(39)-exendin-4. The tumor-targeting characters of the tracer were evaluated in INS-1 cells and BALB/c nude mice models.Results: [F-18]AlF-NOTA-MAL-Cys(39)-exendin-4 can be efficiently produced with a yield of 17.53.2% (non-decay corrected) and radiochemical purity of >95%. The IC50 value of displacement [F-18]AlF-NOTA-MAL-Cys(39)-exendin-4 with Cys(39)-exendin-4 was 13.52 +/- 1.36nM. PET images showed excellent tumor visualization with high uptake (9.15 +/- 1.6%ID/g at 30min and 7.74 +/- 0.87%ID/g at 60min). The tumor to muscle, pancreas and liver ratios were 63.25, 3.85 and 7.29 at 60min after injection. GLP-1R binding specificity was demonstrated by co-injection with an excess of unlabeled Cys(39)-exendin-4 and the tumor uptake was found to be reduced significantly.Conclusion: [F-18]AlF-NOTA-MAL-Cys(39)-exendin-4 shows favorable characteristics for insulinoma imaging and may be translated to clinical studies.