Glucagon-like peptide 1 receptor (GLP-1R) is highly expressed in pancreatic islets, especially on beta cells. Therefore, a properly labeled molecule that binds to GLP-1R could be used for pancreatic islet imaging. Because native GLP-1 is degraded rapidly, a more stable binding molecule such as Exendin-4 is a preferred imaging agent. After radioactive labeling, biodistribution studies and microPET imaging using Exendin-4 were performed in islet transplantation models. GLP-1R positive organs, such as pancreas and lung, showed high uptake. In the intraportal islet transplantation models, labeled Exendin-4 demonstrated almost two times higher uptake compared with normal mice. 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 human subjects.
Wu, Z., et al. (2011). In vivo imaging of transplanted islets with 64Cu-DO3A-VS-Cys40-Exendin-4 by targeting GLP-1 receptor. Bioconjug Chem. 22(8):1587-94.
Ramifications for Individuals with Type 1 Diabetes:
There are currently very few unique markers on beta cells that would be useful for beta cell imaging. This work shows that GLP-1 receptor is a potential target for beta cell imaging.
This work was supported by a JDRF grant to Dr. Kandeel and Dr. Fraser.