Circulation. 2003;108:2270-2274
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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(Circulation. 2003;108:2270.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Molecular Imaging of Angiogenesis in Early-Stage Atherosclerosis With 
vß3-Integrin–Targeted Nanoparticles
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.
Correspondence to Samuel A. Wickline, MD, or Gregory M. Lanza, MD, PhD, Washington University School of Medicine, Campus Box 8086, 660 S Euclid Ave, St Louis, MO 63110. E-mail saw{at}howdy.wustl.edu
Received April 18, 2003; revision received July 7, 2003; accepted July 7, 2003.
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 
80 days. 
vß3-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 vß3-targeted, paramagnetic nanoparticles. Pretreatment of atherosclerotic rabbits with vß3-targeted, nonparamagnetic nanoparticles competitively blocked specific contrast enhancement of the vß3-targeted paramagnetic agent. MRI revealed a pattern of increased vß3-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.
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.
Key Words: magnetic resonance imaging • atherosclerosis • contrast media • angiogenesis
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