Publication Details (including relevant citation information):
Haokao Gao, Gang Niu, Min Yang, Qimeng Quan, Ying Ma, Eunice N. Murage,
Jung-Mo Ahn, Dale O. Kiesewetter, and Xiaoyuan Chen, . Mol. Pharmaceuticals, 2011, 8, 1775-1782.
In this study, we labeled a novel GLP-1 analogue, EM3106B, with 18F and performed PET imaging to visualize insulinoma tumors in an animal model. A GLP-1 analogue that contains multiple lactam bridges, EM3106B, was labeled with 18F through a maleimide-based prosthetic group,N-2-(4-18F-fluorobenzamido)ethylmaleimide (18F-FBEM). The newly developed radiotracer was characterized by cell based receptor-binding assay, cell uptake and efflux assay. The stability in serum was evaluated by radio-HPLC analysis. In vivo PET imaging was performed in nude mice bearing subcutaneous INS-1 insulinoma tumors and MDA-MB-435 tumors of melanoma origin. Ex vivo biodistribution study was performed to confirm the PET imaging data. EM3106B showed high binding affinity (IC50 = 1.38 nM) and high cell uptake (5.25 ( 0.61% after 120 min incubation). 18F-FBEM conjugation of EM3106B resulted in high labeling yield (24.9 ( 2.4%) and high specific activity (>75 GBq/μmol at the end of bombardment). EM3106B specifically bound and was internalized by GLP-1R positive INS-1 cells. After intravenous injection of 3.7MBq (100 μCi) of 18F-FBEM-EM3106B, the
INS-1 tumors were clearly visible with high contrast in relation to the contralateral background on PET images, and tumor uptake of
18F-FBEM-EM3106B was determined to be 28.5(4.7 and 25.4(4.1% ID/g at 60 and 120 min, respectively. 18F-FBEM-EM3106B showed low uptake in MB-MDA-435 tumors with low level of GLP-1R expression. Direct tissue sampling biodistribution experiment confirmed high tracer uptake in INS-1 tumors and receptor specificity in both INS-1 tumor and pancreas. In conclusion, 18F-FBEM-EM3106B exhibited GLP-1R-receptor-specific targeting properties in insulinomas. The favorable characteristics of 18F-FBEM-EM3106B, such as high specific activity and high tumor uptake, and high tumor to nontarget uptake, demonstrate that it is a promising tracer for clinical insulinoma imaging.