In Vivo Imaging of Transplanted Islets with 64Cu-DO3A-VS-Cys40-Exendin-4 by Targeting GLP-1 Receptor

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• 作者：Zhanhong Wu ; Ivan Todorov ; Lin Li ; James R. Bading ; Zibo Li ; Indu Nair ; Kohei Ishiyama ; David Colcher ; Peter E. Conti ; Scott E. Fraser ; John E. Shively ; Fouad Kandeel
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：August 17, 2011
• 年：2011
• 卷：22
• 期：8
• 页码：1587-1594
• 全文大小：980K
• 年卷期：v.22,no.8(August 17, 2011)
• ISSN：1520-4812

文摘

Glucagon-like peptide 1 receptor (GLP-1R) is highly expressed in pancreatic islets, especially on 尾-cells. Therefore, a properly labeled ligand that binds to GLP-1R could be used for in vivo pancreatic islet imaging. Because native GLP-1 is degraded rapidly by dipeptidyl peptidase-IV (DPP-IV), a more stable agonist of GLP-1 such as Exendin-4 is a preferred imaging agent. In this study, DO3A-VS-Cys⁴⁰-Exendin-4 was prepared through the conjugation of DO3A-VS with Cys⁴⁰-Exendin-4. The in vitro binding affinity of DO3A-VS-Cys⁴⁰-Exendin-4 was evaluated in INS-1 cells, which overexpress GLP-1R. After ⁶⁴Cu labeling, biodistribution studies and microPET imaging of ⁶⁴Cu-DO3A-VS-Cys⁴⁰-Exendin-4 were performed on both subcutaneous INS-1 tumors and islet transplantation models. The subcutaneous INS-1 tumor was clearly visualized with microPET imaging after the injection of ⁶⁴Cu-DO3A-VS-Cys⁴⁰-Exendin-4. GLP-1R positive organs, such as pancreas and lung, showed high uptake. Tumor uptake was saturable, reduced dramatically by a 20-fold excess of unlabeled Exendin-4. In the intraportal islet transplantation models, ⁶⁴Cu-DO3A-VS-Cys⁴⁰-Exendin-4 demonstrated almost two times higher uptake compared with normal mice. ⁶⁴Cu-DO3A-VS-Cys⁴⁰-Exendin-4 demonstrated persistent and specific uptake in the mouse pancreas, the subcutaneous insulinoma mouse model, and the intraportal human islet transplantation mouse model. This novel PET probe may be suitable for in vivo pancreatic islets imaging in the human.