Abstract 12091: 18F-fluorodeoxyglucose Uptake Reflects Thrombus Formation and Tissue Factor Expression via Nuclear Factor-κB in Rabbit Atherosclerotic Lesions

Abstract

Introduction: The uptake of ¹⁸F-fluorodeoxyglucose (FDG) in atherosclerotic plaques is detected by positron emission tomography (PET) imaging. However, its significance with respect to atherothrombus formation remains unknown. Hypothesis: We assessed the hypothesis that ¹⁸F-FDG uptake reflects thrombus formation in rabbit atherosclerotic arteries.

Methods: Atherosclerotic plaque was induced in the rabbit iliac-femoral artery by balloon injury and feeding with a diet containing 0.5% cholesterol. The arteries were visualized by ¹⁸F-FDG PET imaging two hours after an ¹⁸F-FDG infusion, and then arterial thrombus was induced by a second balloon injury of the arteries. Fifteen minutes after the second balloon injury, serial sections of the arteries were immunohistochemically and autoradiographically assessed. Tissue factor (TF) expression was measured in cultured atherosclerotic plaques in vitro.

Results: Imaging with ¹⁸F-FDG PET revealed significantly higher radioactivity accumulation along the atherosclerotic (0.063 ± 0.012 %ID × kg/g), than the contralateral normal artery (0.035± 0.008 %ID × kg/g, n = 12, p < 0.0001). The amount of tracer in the excised artery was higher in atherosclerotic, than in normal areas of the artery. Arterial radioactivity measured by autoradiography positively correlated with macrophage area, the number of nuclei that were immunopositive for nuclear factor (NF)-κB, and TF expression. The immunopositive areas for glycoprotein IIb/IIIa and fibrin in thrombi were significantly larger in atherosclerotic, than in normal arteries, and significantly correlated with radioactivity in PET (r = 0.88, p < 0.01, n = 8) and autoradiography (r = 0.65, p < 0.0001, n = 48) in the arteries. The inhibition of NF-κB significantly reduced TF expression in atherosclerotic plaque tissues.

Conclusion: The results suggest that arterial ¹⁸F-FDG uptake reflects the thrombogenicity of atherosclerotic plaques.