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

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

doi:10.2337/db13-1543

journal article Open Access Apr 12, 2014

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

Ping Wang

Byunghee Yoo Jingsheng Yang Xueli Zhang

Alana Ross Pamela Pantazopoulos Guangping Dai Anna Moore

Diabetes Vol. 63 No. 5 pp. 1465-1474 · American Diabetes Association

View at Publisher Save 10.2337/db13-1543

Abstract

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.

Topics

No keywords indexed for this article. Browse by subject →

References

57

[1]

Mukai "GLP-1 receptor antagonist as a potential probe for pancreatic beta-cell imaging" Biochem Biophys Res Commun (2009) 10.1016/j.bbrc.2009.09.014

[2]

Mathis "beta-Cell death during progression to diabetes" Nature (2001) 10.1038/414792a

[3]

Fu "Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging" Nat Immunol (2012) 10.1038/ni.2233

[4]

Wang "Translational molecular imaging of diabetes" Curr Radiol Rep (2013) 10.1007/s40134-013-0019-7

[5]

Andralojc "Obstacles on the way to the clinical visualisation of beta cells: looking for the Aeneas of molecular imaging to navigate between Scylla and Charybdis" Diabetologia (2012) 10.1007/s00125-012-2491-7

[6]

Nauck "Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients" Diabetologia (1993) 10.1007/bf00401145

[7]

Rachman "Normalization of insulin responses to glucose by overnight infusion of glucagon-like peptide 1 (7-36) amide in patients with NIDDM" Diabetes (1996) 10.2337/diab.45.11.1524

[8]

Kim "Mono-PEGylated dimeric exendin-4 as high receptor binding and long-acting conjugates for type 2 anti-diabetes therapeutics" Bioconjug Chem (2011) 10.1021/bc100404x

[9]

Reiner "Near-infrared fluorescent probe for imaging of pancreatic beta cells" Bioconjug Chem (2010) 10.1021/bc100184w

[10]

Reiner "Accurate measurement of pancreatic islet beta-cell mass using a second-generation fluorescent exendin-4 analog" Proc Natl Acad Sci U S A (2011) 10.1073/pnas.1109859108

[11]

Wang "Synthesis and evaluation of [18F]exendin (9-39) as a potential biomarker to measure pancreatic β-cell mass" Nucl Med Biol (2012) 10.1016/j.nucmedbio.2011.07.011

[12]

Selvaraju "In vivo imaging of the glucagonlike peptide 1 receptor in the pancreas with 68Ga-labeled DO3A-exendin-4" J Nucl Med (2013) 10.2967/jnumed.112.114066

[13]

Pattou "GLP-1-receptor scanning for imaging of human beta cells transplanted in muscle" N Engl J Med (2010) 10.1056/nejmc1004547

[14]

Wu "In vivo imaging of transplanted islets with 64Cu-DO3A-VS-Cys40-Exendin-4 by targeting GLP-1 receptor" Bioconjug Chem (2011) 10.1021/bc200132t

[15]

Wu "Development and evaluation of 18F-TTCO-Cys40-Exendin-4: a PET probe for imaging transplanted islets" J Nucl Med (2013) 10.2967/jnumed.112.109694

[16]

Wild "[Lys40(Ahx-DTPA-111In)NH2]exendin-4, a very promising ligand for glucagon-like peptide-1 (GLP-1) receptor targeting" J Nucl Med (2006)

[17]

Christ "Glucagon-like peptide-1 receptor imaging for localization of insulinomas" J Clin Endocrinol Metab (2009) 10.1210/jc.2009-1082

[18]

Wild "Exendin-4-based radiopharmaceuticals for glucagonlike peptide-1 receptor PET/CT and SPECT/CT" J Nucl Med (2010) 10.2967/jnumed.110.074914

[19]

Kiesewetter "18F-radiolabeled analogs of exendin-4 for PET imaging of GLP-1 in insulinoma" Eur J Nucl Med Mol Imaging (2012) 10.1007/s00259-011-1980-0

[20]

Kiesewetter "Evaluation of an [(18)F]AlF-NOTA Analog of Exendin-4 for imaging of GLP-1 receptor in insulinoma" Theranostics (2012) 10.7150/thno.5276

[21]

Sowa-Staszczak "Glucagon-like peptide-1 receptor imaging with [Lys40(Ahx-HYNIC- 99mTc/EDDA)NH2]-exendin-4 for the detection of insulinoma" Eur J Nucl Med Mol Imaging (2013) 10.1007/s00259-012-2299-1

[22]

Zhang "The role of exendin-4-conjugated superparamagnetic iron oxide nanoparticles in beta-cell-targeted MRI" Biomaterials (2013) 10.1016/j.biomaterials.2013.04.021

[23]

Lunov "Modeling receptor-mediated endocytosis of polymer-functionalized iron oxide nanoparticles by human macrophages" Biomaterials (2011) 10.1016/j.biomaterials.2010.08.111

[24]

Duncan "Endocytosis and intracellular trafficking as gateways for nanomedicine delivery: opportunities and challenges" Mol Pharm (2012) 10.1021/mp300293n

[25]

Tornehave "Expression of the GLP-1 receptor in mouse, rat, and human pancreas" J Histochem Cytochem (2008) 10.1369/jhc.2008.951319

[26]

[27]

Zmuda "A method for murine islet isolation and subcapsular kidney transplantation" J Vis Exp (2011) 10.3791/2096

[28]

Medarova "In vivo multimodal imaging of transplanted pancreatic islets" Nat Protoc (2006) 10.1038/nprot.2006.63

[29]

Wang "Combined small interfering RNA therapy and in vivo magnetic resonance imaging in islet transplantation" Diabetes (2011) 10.2337/db10-1400

[30]

Wang "A theranostic small interfering RNA nanoprobe protects pancreatic islet grafts from adoptively transferred immune rejection" Diabetes (2012) 10.2337/db12-0441

[31]

Jin "A new orally available glucagon-like peptide-1 receptor agonist, biotinylated exendin-4, displays improved hypoglycemic effects in db/db mice" J Control Release (2009) 10.1016/j.jconrel.2008.09.091

[32]

Chae "The fatty acid conjugated exendin-4 analogs for type 2 antidiabetic therapeutics" J Control Release (2010) 10.1016/j.jconrel.2010.01.024

[33]

Wunderbaldinger "Crosslinked iron oxides (CLIO): a new platform for the development of targeted MR contrast agents" Acad Radiol (2002) 10.1016/s1076-6332(03)80210-6

[34]

Moore "In vivo targeting of underglycosylated MUC-1 tumor antigen using a multimodal imaging probe" Cancer Res (2004) 10.1158/0008-5472.can-03-3230

[35]

Moore "Tumoral distribution of long-circulating dextran-coated iron oxide nanoparticles in a rodent model" Radiology (2000) 10.1148/radiology.214.2.r00fe19568

[36]

Bourrinet "Preclinical safety and pharmacokinetic profile of ferumoxtran-10, an ultrasmall superparamagnetic iron oxide magnetic resonance contrast agent" Invest Radiol (2006) 10.1097/01.rli.0000197669.80475.dd

[37]

Ban "Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways" Circulation (2008) 10.1161/circulationaha.107.739938

[38]

Kedees "Functional activity of murine intestinal mucosal cells is regulated by the glucagon-like peptide-1 receptor" Peptides (2013) 10.1016/j.peptides.2013.07.022

[39]

Richards "Identification and characterization of GLP-1 receptor–expressing cells using a new transgenic mouse model" Diabetes (2014) 10.2337/db13-1440

[40]

Arifin "Imaging of pancreatic islet cells" Diabetes Metab Res Rev (2011) 10.1002/dmrr.1248

[41]

Antkowiak "Manganese-enhanced magnetic resonance imaging detects declining pancreatic β-cell mass in a cyclophosphamide-accelerated mouse model of type 1 diabetes" Diabetes (2013) 10.2337/db12-0153

[42]

Lubag "Noninvasive MRI of β-cell function using a Zn2+-responsive contrast agent" Proc Natl Acad Sci U S A (2011) 10.1073/pnas.1109649108

[43]

Canton "Endocytosis at the nanoscale" Chem Soc Rev (2012) 10.1039/c2cs15309b

[44]

Yuan "Variable nanoparticle-cell adhesion strength regulates cellular uptake" Phys Rev Lett (2010) 10.1103/physrevlett.105.138101

[45]

Evgenov "In vivo imaging of islet transplantation" Nat Med (2006) 10.1038/nm1316

[46]

Evgenov "In vivo imaging of immune rejection in transplanted pancreatic islets" Diabetes (2006) 10.2337/db06-0484

[47]

Medarova "In vivo imaging of autologous islet grafts in the liver and under the kidney capsule in non-human primates" Transplantation (2009) 10.1097/tp.0b013e3181a5cbc0

[48]

[49]

Denis "Imaging inflammation of the pancreatic islets in type 1 diabetes" Proc Natl Acad Sci U S A (2004) 10.1073/pnas.0404307101

[50]

Turvey "Noninvasive imaging of pancreatic inflammation and its reversal in type 1 diabetes" J Clin Invest (2005) 10.1172/jci25048

Showing 50 of 57 references

Cited By

64

A quantitative design framework for ROS-responsive, hypersensitive materials targeting pancreatic β cells

Xingqi Zhao, Chao Wang · 2026

Materials & Design

Metrics

64

Citations

57

References

Details

Published: Apr 12, 2014
Vol/Issue: 63(5)
Pages: 1465-1474
License: View

Authors

P

Ping Wang

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

B

Byunghee Yoo

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

J

Jingsheng Yang

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

X

Xueli Zhang

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; Center for Drug Discovery, School of Pharmacy, China Pharmaceutical University, Nanjing, China

A

Alana Ross

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

P

Pamela Pantazopoulos

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

G

Guangping Dai

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

A

Anna Moore

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

Cite This Article

Ping Wang, Byunghee Yoo, Jingsheng Yang, et al. (2014). GLP-1R–Targeting Magnetic Nanoparticles for Pancreatic Islet Imaging. Diabetes, 63(5), 1465-1474. https://doi.org/10.2337/db13-1543

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

You May Also Like