GLP-1R–Targeting Magnetic Nanoparticles for Pancreatic Islet Imaging

Wang, Ping; Yoo, Byunghee; Yang, Jingsheng; Zhang, Xueli; Ross, Alana; Pantazopoulos, Pamela; Dai, Guangping; Moore, Anna

doi:10.2337/db13-1543

GLP-1R–Targeting Magnetic Nanoparticles for Pancreatic Islet Imaging

Journal Article · Wed Apr 23 00:00:00 EDT 2014 · Diabetes

DOI:https://doi.org/10.2337/db13-1543· OSTI ID:1628017

Wang, Ping ^[1]; Yoo, Byunghee ^[2]; Yang, Jingsheng ^[3]; Zhang, Xueli ^[4]; Ross, Alana ^[2]; Pantazopoulos, Pamela ^[2]; Dai, Guangping ^[3]; Moore, Anna ^[2]

Harvard Medical School, Boston, MA (United States). Dept. of Radiology. Athinoula A. Martinos Center for Biomedical Imaging. Molecular Imaging Lab.; DOE/OSTI
Harvard Medical School, Boston, MA (United States). Dept. of Radiology. Athinoula A. Martinos Center for Biomedical Imaging. Molecular Imaging Lab.
Harvard Medical School, Boston, MA (United States). Massachusetts General Hospital. Dept. of Radiology. Athinoula A. Martinos Center for Biomedical Imaging
Harvard Medical School, Boston, MA (United States). Dept. of Radiology. Athinoula A. Martinos Center for Biomedical Imaging. Molecular Imaging Lab.; China Pharmaceutical Univ., Nanjing (China). School of Pharmacy. Center for Drug Discovery

Noninvasive assessment of pancreatic b-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 (GLP1R), which is highly expressed on the surface of pancreatic b-cells. In vitro studies in βTC-6, the b-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.

View Accepted Manuscript (DOE)

Research Organization:: Massachusetts General Hospital, Boston, MA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: SC0008430

OSTI ID:: 1628017

Journal Information:: Diabetes, Journal Name: Diabetes Journal Issue: 5 Vol. 63; ISSN 0012-1797

Publisher:: American Diabetes AssociationCopyright Statement

Country of Publication:: United States

Language:: English

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