on October 13, 2003
Circulation. 2003
Published online before print October 13, 2003, doi: 10.1161/01.CIR.0000093185.16083.95
Published online before print October 13, 2003, doi: 10.1161/01.CIR.0000093185.16083.95
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Submitted on April 18, 2003
From the Cardiovascular Magnetic Resonance Laboratories (P.M.W., A.M.M., S.D.C., R.W.F., H.Z., T.A.W., J.S.A., E.K.L., G.M.L., S.A.W.), Department of Medicine, Washington University School of Medicine, St Louis, Mo; Philips Medical Systems (S.D.C.), Best, the Netherlands; and the University of Missouri Research Reactor (J.D.R.), Columbia, Mo. * To whom correspondence should be addressed. E-mail: saw{at}howdy.wustl.edu.
Background--Angiogenesis is a critical feature of plaque development in atherosclerosis and might play a key role in both the initiation and later rupture of plaques that lead to myocardial infarction and stroke. The precursory molecular or cellular events that initiate plaque growth and that ultimately contribute to plaque instability, however, cannot be detected directly with any current diagnostic modality. Methods and Results--Atherosclerosis was induced in New Zealand White rabbits fed 1% cholesterol for Conclusions--This molecular imaging approach might provide a method for defining the burden and evolution of atherosclerosis in susceptible individuals as well as responsiveness of individual patients to antiatherosclerotic therapies.
Revised on July 7, 2003
Accepted on July 7, 2003
Molecular Imaging of Angiogenesis in Early-Stage Atherosclerosis With
Patrick M. Winter PhD, 
v
3-Integrin-Targeted Nanoparticles
80 days. 
v
3-Integrin-targeted, paramagnetic nanoparticles were injected intravenously and provided specific detection of the neovasculature within 2 hours by routine magnetic resonance imaging (MRI) at a clinically relevant field strength (1.5 T). Increased angiogenesis was detected as a 47±5% enhancement in MRI signal averaged throughout the abdominal aortic wall among rabbits that received v3-targeted, paramagnetic nanoparticles. Pretreatment of atherosclerotic rabbits with v3-targeted, nonparamagnetic nanoparticles competitively blocked specific contrast enhancement of the v3-targeted paramagnetic agent. MRI revealed a pattern of increased v3-integrin distribution within the atherosclerotic wall that was spatially heterogeneous along both transverse and longitudinal planes of the abdominal aorta. Histology and immunohistochemistry confirmed marked proliferation of angiogenic vessels within the aortic adventitia, coincident with prominent, neointimal proliferation among cholesterol-fed, atherosclerotic rabbits in comparison with sparse incidence of neovasculature in the control animals.
Key words: magnetic resonance imaging • atherosclerosis • contrast media • angiogenesis
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