Abstract
INTRODUCTION: Rupture of unstable atherosclerotic plaque that leads to stroke and myocardial infarction may be induced by macrophage infiltration and neovessel formation. A tracer that selectively binds to integrin αvβ3 a protein expressed by macrophages and neovascular endothelium may identify rupture prone plaque. METHODS: (18)F-labeled "R-G-D" containing tripeptide (Flotegatide), a click chemistry derived radiotracer that binds to integrin αvβ3 was injected in ApoE knockout mice fed a high fat diet. Uptake of Flotegatide by atherosclerotic plaque was visualized by micro-PET, autoradiography, and correlated to histologic markers of inflammation and angiogenesis. RESULTS: We found that Flotegatide preferentially binds to aortic plaque in an ApoE knockout mouse model of atherosclerosis. The tracer's uptake is strongly associated with presence of histologic markers for macrophage infiltration and integrin expression. There is a weaker but detectable association between Flotegatide uptake and presence of an immunohistochemical marker for neovascularization. DISCUSSION: We hypothesize that Flotegatide may be a useful tracer for visualization of inflamed plaque in clinical subjects with atherosclerosis and may have potential for detecting vulnerable plaque.