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In Vivo Imaging of Transplanted Islets with ^(64)Cu-DO3A-VS-Cys^(40)-Exendin-4 by Targeting GLP-1 Receptor

Wu, Zhanhong and Todorov, Ivan and Li, Lin and Bading, James R. and Li, Zibo and Nair, Indu and Ishiyama, Kohei and Colcher, David and Conti, Peter E. and Fraser, Scott E. and Shively, John E. and Kandeel, Fouad (2011) In Vivo Imaging of Transplanted Islets with ^(64)Cu-DO3A-VS-Cys^(40)-Exendin-4 by Targeting GLP-1 Receptor. Bioconjugate Chemistry, 22 (8). pp. 1587-1594. ISSN 1043-1802.

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Glucagon-like peptide 1 receptor (GLP-1R) is highly expressed in pancreatic islets, especially on β-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-Cys^(40)-Exendin-4 was prepared through the conjugation of DO3A-VS with Cys^(40)-Exendin-4. The in vitro binding affinity of DO3A-VS-Cys^(40)-Exendin-4 was evaluated in INS-1 cells, which overexpress GLP-1R. After ^(64)Cu labeling, biodistribution studies and microPET imaging of ^(64)Cu-DO3A-VS-Cys^(40)-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 ^(64)Cu-DO3A-VS-Cys^(40)-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, ^(64)Cu-DO3A-VS-Cys^(40)-Exendin-4 demonstrated almost two times higher uptake compared with normal mice. ^(64)Cu-DO3A-VS-Cys^(40)-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.

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Fraser, Scott E.0000-0002-5377-0223
Additional Information:© 2011 American Chemical Society. Received: March 15, 2011. Revised: June 20, 2011. Publication Date (Web): June 21, 2011. This work was supported by the grant from the Juvenile Diabetes Research Foundation International (JDRF-37-2009-20). The authors thank Dr. Ismail Al-Abdullah and the islet isolation team of the Southern California Islet Cell Resource Center at City of Hope for providing the human islets.
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Juvenile Diabetes Research Foundation InternationalJDRF-37-2009-20
Issue or Number:8
Record Number:CaltechAUTHORS:20110912-115321956
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Official Citation:In Vivo Imaging of Transplanted Islets with 64Cu-DO3A-VS-Cys40-Exendin-4 by Targeting GLP-1 Receptor 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 Bioconjugate Chemistry 2011 22 (8), 1587-1594
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:25307
Deposited By: Ruth Sustaita
Deposited On:13 Sep 2011 16:29
Last Modified:03 Oct 2019 03:04

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