GLP-1R-targeting magnetic nanoparticles for pancreatic islet imaging
Non-invasive assessment of pancreatic beta-cell mass would tremendously aid in managing type 1 diabetes. Towards this goal we synthesized an exendin-4 conjugated magnetic iron oxide based nanoparticle probe targeting glucagon-like peptide-1 receptor (GLP-1R), which is highly expressed on the surface of pancreatic beta-cells. In vitro studies in βTC-6 beta-cell line showed specific accumulation of the targeted probe (termed MN-Ex10-Cy5.5) compared to non-targeted (termed MN-Cy5.5). In vivo MR imaging showed a significant T2 shortening in the pancreas of mice injected with MN-Ex10-Cy5.5 probe compared to control animals injected with non-targeted probe at 7.5 and 24 h after injection. Furthermore, ΔT2 of the panceata of pre-diabetic NOD mice was significantly higher than that of diabetic NOD mice after the injection of MN-Ex10-Cy5.5, indicating the decrease of probe accumulation in these animals due to beta-cell loss. Noteworthy, ΔT2 of pre-diabetic and diabetic NOD mice injected with MN-Cy5.5 was not significantly changed reflecting the non-specific mode of accumulation of non-targeted probe. We believe that our results pointing to the potential for using this agent for monitoring the disease development and response to therapy.
- Received October 7, 2013.
- Accepted January 15, 2014.
- © 2014 by the American Diabetes Association.
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