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In vivo imaging of immuno-spin trapped radicals with molecular magnetic resonance imaging in a diabetic mouse model. Diabetes 2012 Oct;61(10):2405-13

Date

06/16/2012

Pubmed ID

22698922

Pubmed Central ID

PMC3447912

DOI

10.2337/db11-1540

Scopus ID

2-s2.0-84866603867 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

Oxidative stress plays a major role in diabetes. In vivo levels of membrane-bound radicals (MBRs) in a streptozotocin-induced diabetic mouse model were uniquely detected by combining molecular magnetic resonance imaging (mMRI) and immunotrapping techniques. An anti-DMPO (5,5-dimethyl-1-pyrroline N-oxide) antibody (Ab) covalently bound to an albumin (BSA)-Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)-biotin MRI contrast agent (anti-DMPO probe), and mMRI, were used to detect in vivo levels of DMPO-MBR adducts in kidneys, livers, and lungs of diabetic mice, after DMPO administration. Magnetic resonance signal intensities, which increase in the presence of a Gd-based molecular probe, were significantly higher within the livers, kidneys, and lungs of diabetic animals administered the anti-DMPO probe compared with controls. Fluorescence images validated the location of the anti-DMPO probe in excised tissues via conjugation of streptavidin-Cy3, which targeted the probe biotin moiety, and immunohistochemistry was used to validate the presence of DMPO adducts in diabetic mouse livers. This is the first report of noninvasively imaging in vivo levels of MBRs within any disease model. This method can be specifically applied toward diabetes models for in vivo assessment of free radical levels, providing an avenue to more fully understand the role of free radicals in diabetes.

Author List

Towner RA, Smith N, Saunders D, Henderson M, Downum K, Lupu F, Silasi-Mansat R, Ramirez DC, Gomez-Mejiba SE, Bonini MG, Ehrenshaft M, Mason RP



MESH terms used to index this publication - Major topics in bold

Animals
Cell Membrane
Diabetes Mellitus, Experimental
Electron Spin Resonance Spectroscopy
Free Radicals
Magnetic Resonance Imaging
Mice
Mice, Inbred C57BL
Oxidative Stress
Spin Trapping