In vivo imaging of immuno-spin trapped radicals with molecular magnetic resonance imaging in a diabetic mouse model

Rheal A. Towner*, Nataliya Smith, Debra Saunders, Michael Henderson, Kristen Downum, Florea Lupu, Robert Silasi-Mansat, Dario C. Ramirez, Sandra E. Gomez-Mejiba, Marcelo G. Bonini, Marilyn Ehrenshaft, Ronald P. Mason

*Corresponding author for this work

Research output: Contribution to journalArticle

24 Scopus 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.

Original languageEnglish (US)
Pages (from-to)2405-2413
Number of pages9
JournalDiabetes
Volume61
Issue number10
DOIs
StatePublished - Oct 2012
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Towner, R. A., Smith, N., Saunders, D., Henderson, M., Downum, K., Lupu, F., Silasi-Mansat, R., Ramirez, D. C., Gomez-Mejiba, S. E., Bonini, M. G., Ehrenshaft, M., & Mason, R. P. (2012). In vivo imaging of immuno-spin trapped radicals with molecular magnetic resonance imaging in a diabetic mouse model. Diabetes, 61(10), 2405-2413. https://doi.org/10.2337/db11-1540