Development Of [sup Supra> 18 F] AlF-NOTA-MAL-Cys ³⁹ -exendin-4 And Imaging Studies In Insulinoma

Purpose:To prepare [18F]AlF-NOTA-MAL-Cys39-exendin-4 and evaluate its PET imaging efficacy and distribution in Balb/c nude mice bearing INS-1 tumors.Methods:Cys39-exendin-4 was mixed with NOTA-MAL (1:2) and dissolved in 0.2M ammonium acetate (PH=7.0). After stirring at 40℃ overnight, the mixture was purified by semipreparative HPLC with a linear gradient. The fractions containing NOTA-MAL-Cys39-exendin-4 were collected and lyophilized. A 1mL vial was charged with 6μL of a solution of aluminum chloride (2 mM) in 0.2 M pH 4 sodium acetate buffer. Then, NOTA-MAL-Cys39-exendin-4 (100 fig) in 0.2 M pH 4 sodium acetate buffer was added, followed by cyclotron target water containing [18F]fluoride (740 MBq). The resulting solution was heated at 100℃ for 10 min. The stability of [18F]AlF-NOTA-MAL-Cys39-exendin-4 was tested in human plasma. Characters of the tracer in vitro were performed in INS-1 cells. PET imaging and biodistribution studies were conducted on BALB/c nude mice bearing INS-1 tumors.Results:[18F]AlF-NOTA-MAL-Cys39-exendin-4 can be efficiently produced within 30 min with a yield of 17.5±3.2% (non-decay corrected) and a radiochemical purity of greater than 95%. The imaging agent was stable in human plasma for at least 3 h. The IC50 values of displacement [18F]AlF-NOTA-MAL-Cys39-exendin-4 with Cys39-exendin-4 were 13.52±1.36 nM. Insulinoma xenograft in the animal model was clearly visible with good contrast to background. High uptakes of tumor by quantification of the PET data were determined to be 9.15±1.6,7.74±0.87%ID/g at 30 min,60 min p.i., respectively. GLP-1R binding specificity was demonstrated by coinjection an excess of unlabeled Cys39-exendin-4 with [18F]AlF-NOTA-MAL-Cys39-exendin-4 and INS-1 tumor uptake was found to be reduced. [18F]AlF-NOTA-MAL-Cys39-exendin-4 uptake was also found in pancreas and lungs. However, compared with tumor, the uptake in pancreas and lungs was distinctly lower. The tumor to muscle, pancreas and liver ratios were 63.25,3.85 and 7.29 at 60 min respectively after injection.Conclusion:[18F]AlF-NOTA-MAL-Cys39-exendin-4 could be prepared in a simple procedure with high radiochemical purity. The radiotracer shows favorable characteristics such as ideal biodistribution and good targetability. Therefore, it is a promise tracer for insulinoma imaging.