Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha(v)beta3-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 approximately 80 days. alpha(v)beta3-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 alpha(v)beta3-targeted, paramagnetic nanoparticles. Pretreatment of atherosclerotic rabbits with alpha(v)beta3-targeted, nonparamagnetic nanoparticles competitively blocked specific contrast enhancement of the alpha(v)beta3-targeted paramagnetic agent. MRI revealed a pattern of increased alpha(v)beta3-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.

journal_name

Circulation

journal_title

Circulation

authors

Winter PM,Morawski AM,Caruthers SD,Fuhrhop RW,Zhang H,Williams TA,Allen JS,Lacy EK,Robertson JD,Lanza GM,Wickline SA

doi

10.1161/01.CIR.0000093185.16083.95

subject

Has Abstract

pub_date

2003-11-04 00:00:00

pages

2270-4

issue

18

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000093185.16083.95

journal_volume

108

pub_type

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