title: In vivo targeted molecular magnetic resonance imaging of free radicals in diabetic cardiomyopathy within mice.
abstract: Free radicals contribute to the pathogenesis of diabetic cardiomyopathy. We present a method for in vivo observation of free radical events within murine diabetic cardiomyopathy. This study reports on in vivo imaging of protein/lipid radicals using molecular MRI (mMRI) and immuno-spin trapping (IST) in diabetic cardiac muscle. To detect free radicals in diabetic cardiomyopathy, streptozotocin (STZ)-exposed mice were given 5,5-dimethyl-pyrroline-N-oxide (DMPO) and administered an anti-DMPO probe (biotin-anti-DMPO antibody-albumin-Gd-DTPA). For controls, non-diabetic mice were given DMPO (non-disease control), and administered an anti-DMPO probe; or diabetic mice were given DMPO but administered a non-specific IgG contrast agent instead of the anti-DMPO probe. DMPO administration started at 7 weeks following STZ treatment for 5 days, and the anti-DMPO probe was administered at 8 weeks for MRI detection. MRI was used to detect a significant increase (p < 0.001) in MRI signal intensity (SI) from anti-DMPO nitrone adducts in diabetic murine left-ventricular (LV) cardiac tissue, compared to controls. Regional increases in MR SI in the LV were found in the apical and upper-left areas (p < 0.01 for both), compared to controls. The biotin moiety of the anti-DMPO probe was targeted with fluorescently-labeled streptavidin to locate the anti-DMPO probe in excised cardiac tissues, which indicated elevated fluorescence only in cardiac muscle of mice administered the anti-DMPO probe. Oxidized lipids and proteins were also found to be significantly elevated (p < 0.05 for both) in diabetic cardiac muscle compared to controls. It can be concluded that diabetic mice have more heterogeneously distributed radicals in cardiac tissue than non-diabetic mice.
authors.affiliation: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation , Oklahoma City, OK , USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Towner
authors.forename: N
authors.initials: N
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Saunders
authors.forename: J
authors.initials: J
authors.lastname: Carrizales
authors.forename: F
authors.initials: F
authors.lastname: Lupu
authors.forename: R
authors.initials: R
authors.lastname: Silasi-Mansat
authors.forename: M
authors.initials: M
authors.lastname: Ehrenshaft
authors.forename: R P
authors.initials: RP
authors.lastname: Mason
mesh_terms: D000418:Albumins / Q000737:chemistry; D000818:Animals; D003287:Contrast Media / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000473:pathology*; D005609:Free Radicals / Q000737:chemistry; D019786:Gadolinium DTPA / Q000737:chemistry; D006352:Heart Ventricles / Q000473:pathology; D008055:Lipids / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008956:Models, Chemical; D032383:Myocytes, Cardiac / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D019097:Spin Trapping; D013311:Streptozocin
chemical_list: D000418:Albumins; D003287:Contrast Media; D003497:Cyclic N-Oxides; D005609:Free Radicals; D008055:Lipids; C058946:albumin-(gadolinium-DTPA); D013311:Streptozocin; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D019786:Gadolinium DTPA; D010100:Oxygen
keywords: free radical targeted imaging; immuno-spin trapping; in vivo; mice; streptozotocin