期刊
DIABETES
卷 63, 期 5, 页码 1465-1474出版社
AMER DIABETES ASSOC
DOI: 10.2337/db13-1543
关键词
-
资金
- JDRF [JDRF 37-2009-30]
- Harvard/Massachusetts General Hospital Nuclear Medicine Training Program - U.S. Department of Energy [DE-SC0008430]
Noninvasive assessment of pancreatic -cell mass would tremendously aid in managing type 1 diabetes (T1D). Toward 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 -cells. In vitro studies in TC-6, the -cell line, showed specific accumulation of the targeted probe (termed MN-Ex10-Cy5.5) compared with nontargeted (termed MN-Cy5.5). In vivo magnetic resonance imaging showed a significant transverse relaxation time (T2) shortening in the pancreata of mice injected with the MN-Ex10-Cy5.5 probe compared with control animals injected with the nontargeted probe at 7.5 and 24 h after injection. Furthermore, T2 of the pancreata of prediabetic 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 -cell loss. Of note, T2 of prediabetic and diabetic NOD mice injected with MN-Cy5.5 was not significantly changed, reflecting the nonspecific mode of accumulation of nontargeted probe. We believe our results point to the potential for using this agent for monitoring the disease development and response of T1D to therapy.
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