IN VIVO IMAGING OF IMMUNO-SPIN TRAPPED RADICALS WITH MOLECULAR MRI IN A MOUSE DIABETES MODEL

RHEAL A. TOWNER; NATALIYA SMITH; SAUNDERS, DEBORAH; HENDERSON, M; DOWNUM, K.; FLOREA, LUPU; SILASI-MANSAT, R.; DARIO C. RAMIREZ; SANDRA E. GOMEZ-MEJIBA; MARCELO G. BONINI; EHRENSHAFT MARILYN; RONALD P. MASON

DIABETES

AMER DIABETES ASSOC

Año: 2012 vol. 61 p. 2405 - 2413

0012-1797

Oxidative stress plays a major role in diabetes. In vivo levels ofmembrane-bound radicals (MBR) in a streptozotocin-induceddiabetic mouse model were uniquely detected by combiningmolecular magnetic resonance imaging (mMRI) and immunotrappingtechniques. 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 contrastagent (anti-DMPO probe), and molecular MRI, were used todetect in vivo levels of DMPO-MBR adducts in kidneys, liver,and lungs of diabetic mice, after DMPO administration. MR signalintensities, which increase in the presence of a Gd-based molecularprobe, were significantly higher within the livers, kidneys,and lungs of diabetic animals administered the anti-DMPO probecompared with controls. Fluorescence images validated the locationof the anti-DMPO probe in excised tissues via conjugation ofstreptavidin-Cy3, which targeted the probe biotin moiety, and immunohistochemistrywas used to validate the presence ofDMPO-adducts in diabetic mouse livers. This is the first reportof noninvasively imaging in vivo levels of MBR within any diseasemodel. This method can be specifically applied toward diabetesmodels for in vivo assessment of free radical levels, providing anavenue to more fully understand the role of free radicals indiabetes.