Eunice Murage - PET of Insulinoma Using 18F-FBEM-EM3106B, a New GLP-1 Analogue

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      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.

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