GLP-1R-targeting magnetic nanoparticles for pancreatic islet imaging.
Noninvasive assessment of pancreatic β-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 β-cells. In vitro studies in βTC-6, the β-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, ΔT2 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 β-cell loss. Of note, ΔT2 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.
Molecular Imaging Laboratory, Massachusetts General Hospital/Massachusetts Institute of Technology/Harvard Medical School Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Ping
P
Wang
Byunghee
B
Yoo
Jingsheng
J
Yang
Xueli
X
Zhang
Alana
A
Ross
Pamela
P
Pantazopoulos
Guangping
G
Dai
Anna
A
Moore
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology*; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D018027:Receptors, Glucagon / Q000378:metabolism*
C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D058185:Magnetite Nanoparticles; D018027:Receptors, Glucagon