Session: SAT 326-337-Hormone-Dependent Tumors
Bench to Bedside
Poster Board SAT-333
Methods: The thiol-reactive reagent, 18F vinyl sulfone (18F-DEG-VS), was prepared through one step radio-fluorination. After high-pressure liquid chromatography purification, 18F-DEG-VS was conjugated to the thiolated Exendin-4 peptide (a high affinity ligand towards GLP-1R and metabolically much more stable than GLP-1). The resulting imaging probe (18F-DEG-VS-Exendin-4) was tested for receptor-binding assay and microPET studies in murine xenograft models.
Results: Thiolated exendin-4 peptide could be efficiently labeled with 18F-DEG-VS with 95% labeling yield (decay-corrected on the basis of 18F-DEG-VS). The radiochemical purity of the 18F-DEG-VS-Exendin-4 was >98%. The in vitro cell binding assay of F-DEG-VS-Exendin-4 in INS-1 cells (GLP-1R positive) demonstrated that the conjugation has minimal effect on receptor-binding affinity. Noninvasive microPET demonstrated that 18F-DEG-VS-Exendin-4 had GLP-1R-specific tumor uptake in subcutaneous INS-1 xenografts. The tumor to liver and tumor to kidney ratio could reach 4.26 and 2.23 at 2 hr p.i. respectively. Receptor specificity was successfully demonstrated by blocking experiment.
Conclusions: Through the 18F-vinyl sulfone synthon, a GLP-1R targeted PET imaging agent was synthesized, which demonstrated specific insulinoma uptake and superior tumor to background contrast. The elevated tumor to major organ uptake ratios (including tumor/kidney) lead to high contrast images in vivo. The evaluation in non-human primate will be performed to determin the safety profile of 18F-DEG-VS-Exendin-4 for clinical translation.
Nothing to Disclose: ZW, SL, IN, IT, ZL, JES, FRK
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