Molecular Imaging of Angiogenesis in Early-Stage Atherosclerosis With α v β 3 -Integrin–Targeted Nanoparticles

Abstract

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. αvβ3-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 αvβ3-targeted, paramagnetic nanoparticles. Pretreatment of atherosclerotic rabbits with αvβ3-targeted, nonp...