PET/CT Imaging of Integrin αvβ3 Expression in Human Carotid Atherosclerosis

OBJECTIVES The goal of this study was to evaluate the feasibility of [F-18]Galacto-RGD positron emission tomography (PET)/computed tomography (CT) imaging of alpha v beta 3 expression in human carotid plaques. BACKGROUND The integrin alpha v beta 3 is expressed by macrophages and angiogenic endothelial cells in atherosclerotic lesions and thus is a marker of plaque inflammation and, potentially, of plaque vulnerability. [F-18]Galacto-RGD is a PET tracer binding specifically to alpha v beta 3. Therefore, [F-18]Galacto-RGD PET/CT imaging of alpha v beta 3 expression in human carotid plaques might provide a novel noninvasive biomarker of plaque vulnerability. METHODS [F-18]Galacto-RGD PET/CT imaging was performed in 10 patients with high-grade carotid artery stenosis scheduled for carotid endarterectomy. Tracer uptake was measured in the stenotic areas of the carotid arteries, as well as on the contralateral side, and was corrected for blood pool activity, measured in the distal common carotid artery (target-to-background [TB] ratio). TB ratio was correlated with immunohistochemistry of alpha v beta 3 expression (LM609), macrophage density (CD68), and microvessel density (CD31) of the surgical specimen. In addition, ex vivo autoradiography of the surgical specimen with [F-18]Galacto-RGD and competition experiments with an unlabeled alpha v beta 3-specific RGD peptide were performed. RESULTS [F-18]Galacto-RGD PET/CT showed significantly higher TB ratios in stenotic areas compared with nonstenotic areas (p = 0.01). TB ratios correlated significantly with alpha v beta 3 expression (R = 0.787, p = 0.026) and intensity of ex vivo autoradiography (R = 0.733, p = 0.038). Binding to atherosclerotic plaques was efficiently blocked in ex vivo competition experiments. A weak-to-moderate correlation was found with macrophage density (R = 0.367, p = 0.299) and microvessel density (R = 0.479, p = 0.176), which did not reach statistical significance. CONCLUSIONS [F-18]Galacto-RGD PET/CT shows specific tracer accumulation in human atherosclerotic carotid plaques, which correlates with alpha v beta 3 expression. Based on these initial data, larger prospective studies are now warranted to evaluate the potential of molecular imaging of alpha v beta 3 expression for assessment of plaque inflammation in patients. (J Am Coll Cardiol Img 2014;7:178-87) (C) 2014 by the American College of Cardiology Foundation