Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published August 2011 | Supplemental Material
Journal Article Open

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

Abstract

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.

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.

Attached Files

Supplemental Material - bc200132t_si_001.pdf

Files

bc200132t_si_001.pdf
Files (106.9 kB)
Name Size Download all
md5:fc42e7f4525920edcbd2c906dd10ea36
106.9 kB Preview Download

Additional details

Created:
August 19, 2023
Modified:
October 24, 2023