Abstract 1492: Molecular Imaging Of Occult Kidney Inflammation In ApoE −/− Mice Using 19F MRI Nanobeacons For VCAM-1
Although renal disease has been identified as a comorbidity for late-stage atherosclerosis, the early involvement of renal inflammation in the pathophysiology of progressive atherosclerosis has not yet been defined. To elucidate the impact of hyperlipidemia on incipient kidney disease, we deployed a VCAM-1-specific nanobeacon for magnetic resonance molecular imaging that emits a unique fluorine (19F) signature without any background signal (Figure⇓). A dose of 1ml/kg was given intravenously to 6 cholesterol-fed ApoE −/− and 6 C57BL/6 mice, and VCAM -1 expression was measured after 2 hours at 11.7T ex vivo. Marked diffuse expression of VCAM-1 and macrophage infiltration was observed by immunocytochemistry in glomerular structures, especially in efferent and afferent arterioles. 19F imaging confirmed widespread involvement in the renal cortex (Figure⇓). Magnetic resonance spectroscopic quantification of renal VCAM-1 expression in control (C57BL/6) mice was significantly lower (36.5±8.8 vs. 9.3±2.2x108 NP/g kidney) than that of ApoE−/− mice (p<0.05). These data indicate that 19F-based molecular MRI nanobeacons can detect and quantify renovascular disease in its earliest preclinical stages, and serve as a tool for both prognosis and management of generalized atherosclerosis.
This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).