Abstract 5760: Early Detection of Arteriopathy in Metabolic Syndrome by MR Molecular Imaging with Targeted Nanobeacons
Metabolic syndrome elicits widespread inflammatory changes in vascular structures leading to early atherosclerosis that cannot be detected with classical imaging methods. Because pronounced early angiogenesis within the arterial wall typically accompanies activated inflammatory cells in standard models of atherosclerosis, we hypothesized that the expression of αvβ3-integrins on neovascular endothelium would provide an abundant and sensitive biomarker of the metabolic vasculopathy. The mildly diabetic JCR:LA-cp rat was used as a model for MR molecular imaging of angiogenesis with αvβ3-targeted gadolinium nanoparticles (NP). 5 month-old male JCR:LA-cp lean (control) and obese (affected) rats (n=5 each) were studied. The abdominal aorta was imaged with a 3.0 T clinical MRI scanner and a T1w, fat-suppressed, black-blood imaging sequence. Imaging was performed before (BSL) and 2 hours (2 HR) after NP injection (IV, 1.0 ml/kg). Fat suppressed imaging revealed large abdominal fat deposits in the obese rats but not in controls, concordant with elevated cholesterol levels (~2 times higher) in the obese rats (p<0.05). MRI contrast enhancement of angiogenesis in the aortic wall (Figure⇓: top, arrow) in the obese rats was significantly higher than that in the lean rats (bottom, *p<0.05) indicating the widespread presence of neovasculature despite no apparent stenosis. MR molecular imaging of angiogenesis with integrin-targeted nanoparticles may represent a sensitive high-resolution surrogate signal for detecting early metabolic vasculopathy.
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).