FDG–PET can distinguish inflamed from non-inflamed plaque in an animal model of atherosclerosis

Abstract

The presence of activated macrophages is an important predictor of atherosclerotic plaque rupture. In this study, our aim was to determine the accuracy of (18)F- fluorodeoxyglucose (FDG) microPET imaging for quantifying aortic wall macrophage content in a rabbit model of atherosclerosis. Rabbits were divided into a control group and two groups post aortic balloon injury: 6 months high-cholesterol diet (HC); and 3 months HC followed by 3 months low-cholesterol diet plus statin (LCS). In vivo and ex vivo microPET, ex vivo well counting and histological quantification of the atherosclerotic aortas were performed for all groups. Macrophage density was greater in the HC group than the LCS group (5.1 +/- 1.4% vs. 0.6 +/- 0.7%, P < 0.001) with a trend towards greater macrophage density in LCS compared to controls (P = 0.08). There was a strong correlation across all groups between macrophage density and standardized uptake value (SUV) derived from ex vivo microPET (r = 0.95, P < 0.001) and well counting (r = 0.96, P < 0.001). Ex vivo FDG SUV was significantly different between the three groups (P < 0.001). However, the correlation between in vivo microPET FDG SUV and macrophage density was insignificant (r = 0.16, P = 0.57) with no statistical differences in FDG SUV seen between the three groups. This study confirms that in an animal model of inflamed and non-inflamed atherosclerosis, significant differences in FDG SUV allow differentiation of highly inflamed atherosclerotic aortas from those stabilized by statin therapy and low cholesterol diet and controls.

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

“…Inhibiting NF-κB using Bay 11-7055, an inhibitor of inhibitor of κB kinase, significantly reduced both the number of NF-κB-immunopositive nuclei ( Figure 6A) and TF protein production ( Figure 6B). Staining 23 Macrophages and granulocytes express glucose transporter 1 and hexokinase II in lung inflammatory lesions. 18 F-FDG uptake correlates with the degree of inflammation 24 and lipopolysaccharide enhances 18 F-FDG uptake by isolated human monocyte-macrophages.…”

18F-Fluorodeoxyglucose PET Imaging of Coronary Atherosclerosis and Plaque Inflammation

“…In rabbit models, FDG was shown to be taken up by macrophage-rich atherosclerotic lesions in the aortic arch, and there was a correlation between FDG accumulation in the plaque with local macrophage density [15][16][17][18]. In humans, accumulation of 3H-deoxyglucose was shown in macrophage-rich areas of freshly isolated human carotid plaques [19] along with a significant correlation between FDG PET activity in carotid plaques and macrophage staining from the corresponding histologic sections of post-endarterectomy samples [20].…”

“…Recent studies reported on the potential use of intravascular ultrasonography, CT angiography, MRI, and metabolic 18 F-fluorodeoxyglucose (FDG) imaging with positron emission tomography (PET) for this purpose [5][6][7][8]. A combined functional and structural whole-body imaging will likely afford the best potential for visualizing coronary atherosclerosis and plaque inflammation [8,9].…”

Imaging Intraplaque Inflammation in Carotid Atherosclerosis With 18 F-Fluorocholine Positron Emission Tomography–Computed Tomography

“…[6][7][8][9][10][11][12] However, because FDG is taken up by any metabolically active tissues, including those surrounding atherosclerotic plaques (such as fat, muscles, and lymph nodes), concerns have been raised about the specificity of this tracer for imaging inflammatory cells. Indeed, Davies et al 32 showed that in vivo FDG uptake in atherosclerotic lesions of rabbit aorta does not correlate with macrophage density. They reported no significant difference in FDG uptake between rabbits with highly inflamed aortic walls, those with low levels of inflammation, or controls.…”

“…They reported no significant difference in FDG uptake between rabbits with highly inflamed aortic walls, those with low levels of inflammation, or controls. 32 Moreover, recent clinical data on FDG PET showed an inconsistent correlation between FDG uptake and intraplaque inflammation, ranging from significantly high, 7 medium, 33 to very poor correlation coefficients. 34 Conversely, a high degree of choline uptake in macrophage-rich areas of murine atherosclerotic lesions has been observed with choline in autoradiographic studies, 20 suggesting that 18 F-FCH may provide a more specific tracer to assess active macrophage infiltration.…”