Imaging of vulnerable atherosclerotic plaque with [ 18F]FDG-PET: an animal atherosclerosis model study

Abstract

The rupture of atherosclerotic plaques and the resultant thrombus formation are mainly responsible for myocardial and cerebral infarctions. Thus, the detection of vulnerable plaques in atherosclerotic lesions has been desired, and attempts to image them with [ 18F]FDG are ongoing. Intimal thickening can be observed both in stable and vulnerable plaques; however, in vulnerable plaque, the lesion is inflamed, and the infiltrated macrophages cause the rupture of such plaques. In this study, we investigated whether [ 18F]FDG-PET could specifically detect the vulnerable plaque, other than stable plaque, or not using an animal model of atherosclerosis, the Watanabe heritable hyperlipidemic (WHHL) rabbit. A helical CT angiogram was acquired at 180 min postinjection of [ 18F]FDG, and PET scanning was carried out for 15 min from 210 min postinjection of [ 18F]FDG. At 4 h postinjection of the radiotracer, the aortas were removed, and the radioactivity was measured. Then, each arterial segment was embedded in paraffin, and consecutive 5-μm-thick slices were prepared. They were subjected to Azan–Mallory staining or immunohistochemical staining for measurement of intimal thickness and macrophage number. In the aortas of the WHHL rabbits, intense [ 18F]FDG radioactivity was detected with PET, while little radioactivity was seen in the aortas of control rabbits. Actually, in the removed aortic segments [ 18F]FDG accumulated significantly higher in the aortas of the WHHL rabbits than in those of the control rabbits. Furthermore, in the atherosclerotic lesions of the WHHL rabbits, the [ 18F]FDG uptake was well correlated with macrophage number. On the other hand, the correlation between [ 18F]FDG uptake and the area ratio of the intima to the whole cross-section was poor. These results suggest that the detected radioactivity with [ 18F]FDG-PET in the atherosclerotic lesion is associated with macrophage density. Since macrophages are responsible for plaque vulnerability, [ 18F]FDG imaging should be useful for selective detection of vulnerable plaques.