18F-DEG-VS-Exendin-4 as a PET probe for insulinoma imaging

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 326-337-Hormone-Dependent Tumors
Bench to Bedside
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-333
Zhanhong Wu1, Shuanglong Liu2, Indu Nair1, Ivan Todorov1, Zibo Li2, John E Shively1 and Fouad R Kandeel*1
1City of Hope National Med Ctr, Duarte, CA, 2University of Southern California, Los Angeles, CA
Objective: Insulinoma is a tumor derived from endocrine pancreatic beta cells. The standard treatment for insulinomas is surgical resection, which requires information on exact localization of the tumor lesions. However, the size of insulinoma is usually small making it hard to detect by the current imaging technologies. Glucagon like peptide-1 receptor (GLP-1R) is highly expressed in insulinoma, ligands of GLP-1R could therefore be used as molecular probes for imaging these tumors. In this study, we developed an 18F labeled Exendin-4 for GLP-1R targeted imaging of insulinoma by PET scans.

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

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: The Jonas Brothers Foundation