GLP-1R-targeting magnetic nanoparticles for pancreatic islet imaging
- Ping Wang1,
- Byunghee Yoo1,
- Jingsheng Yang2,
- Xueli Zhang1,3,
- Alana Ross1,
- Pamela Pantazopoulos1,
- Guangping Dai2 and
- Anna Moore1⇑
- 1Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.
- 2MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston.
- 3Center for Drug Discovery, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
- Corresponding author: Anna Moore, Email:
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.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.