Arterial 18F-Fluorodeoxyglucose Uptake Reflects Balloon Catheter-Induced Thrombus Formation and Tissue Factor Expression via Nuclear Factor-κB in Rabbit Atherosclerotic Lesions

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Background: Imaging modalities to assess atherosclerotic plaque thrombogenicity have not been established, so in this study the relationship between [18F]-fluorodeoxyglucose (18F-FDG) uptake and thrombus formation was investigated in rabbit atherosclerotic arteries. Methods and Results: Atherosclerotic plaque was induced in the iliacofemoral artery by balloon injury and a 0.5% cholesterol diet. At 3 weeks after the first balloon injury, the arteries were visualized by 18F-FDG positron emission tomography (PET) imaging 2h after an 18F-FDG infusion, and then arterial thrombus was induced by a second balloon injury of both iliacofemoral arteries. Imaging with 18F-FDG-PET revealed significantly more radioactivity along the injured (0.63±0.12 SUVmax), than the contralateral non-injured artery (0.34±0.08 SUVmax, n=17, P<0.0001). Arterial radioactivity measured by autoradiography positively correlated with macrophage area, the number of nuclei that were immunopositive for nuclear factor κ B (NF-κB), and tissue factor (TF) expression. The immunopositive areas for glycoprotein IIb/IIIa and fibrin in thrombi were significantly larger in the atherosclerotic than in the contralateral arteries, and significantly correlated with radioactivity in PET (r=0.92, P<0.001, n=10) and autoradiography (r=0.73, P<0.0001, n=50) in the arteries. Inhibition of NF-κB significantly reduced TF expression in cultured atherosclerotic plaque. Conclusions: Arterial 18F-FDG uptake reflects the thrombogenicity of atherosclerotic plaque following balloon injury.

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