Correlation between arterial FDG uptake and biomarkers in peripheral artery disease

Abstract

Objectives: A prospective, multicenter (18)fluorine-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging study was performed to estimate the correlations among arterial FDG uptake and atherosclerotic plaque biomarkers in patients with peripheral artery disease.

Background: Inflammation within atherosclerotic plaques is associated with instability of the plaque and future cardiovascular events. Previous studies have shown that (18)F-FDG-PET/CT is able to quantify inflammation within carotid artery atherosclerotic plaques, but no studies to date have investigated this correlation in peripheral arteries with immunohistochemical confirmation.

Methods: Thirty patients across 5 study sites underwent (18)F-FDG-PET/CT imaging before SilverHawk atherectomy (FoxHollow Technologies, Redwood City, California) for symptomatic common or superficial femoral arterial disease. Vascular FDG uptake (expressed as target-to-background ratio) was measured in the carotid arteries and aorta and femoral arteries, including the region of atherectomy. Immunohistochemistry was performed on the excised atherosclerotic plaque extracts, and cluster of differentiation 68 (CD68) level as a measure of macrophage content was determined. Correlations between target-to-background ratio of excised lesions, as well as entire arterial regions, and CD68 levels were determined. Imaging was performed during the 2 weeks before surgery in all cases.

Results: Twenty-one patients had adequate-quality (18)F-FDG-PET/CT peripheral artery images, and 34 plaque specimens were obtained. No significant correlation between lesion target-to-background ratio and CD68 level was observed.

Conclusions: There were no significant correlations between CD68 level (as a measure of macrophage content) and FDG uptake in the peripheral arteries in this multicenter study. Differences in lesion extraction technique, lesion size, the degree of inflammation, and imaging coregistration techniques may have been responsible for the failure to observe the strong correlations with vascular FDG uptake observed in previous studies of the carotid artery and in several animal models of atherosclerosis.

Figure 1. Plaque Histology of SilverHawk Atherectomy Specimens

Representative histology sample of atherosclerotic plaque from a preliminary study extracted by using the SilverHawk technique (FoxHollow Technologies, Redwood City, California) stained with hematoxylin and eosin (H&E), cluster of differentiation 68 (CD68; for macrophages), Elastica-van Gieson ([EVG]; for connective tissue), and Gomori’s Trichrome (for smooth muscle cells [SMC]).

Figure 2. CD68 Versus TBR

Correlation of cluster of differentiation 68 (CD68) (after log transformation for normality) and mean of the maximum target-to-background ratios (max TBR) in the excised femoral lesions. CD68 values from the excised lesion as a measure of macrophage content showed no significant correlation to the max TBR values in the lesion (r = 0.21; p > 0.05).

Figure 3. PET/CT Images in Subjects With High Versus Low CD68 Values

Axial computed tomography (CT), positron emission tomography (PET), and fused PET/CT images are shown from left to right, respectively, in the region of the excised lesion for subjects with (A) a lower cluster of differentiation 68 (CD68) value (CD68 value of 1.08 [about 1 SD below the mean]) and (B) a higher CD68 value (CD68 value of 1.4 [about 1 SD above the mean]). No correlation between CD68 content and mean of the maximum target-to-background ratios (max TBR) in the excised lesions was found (p > 0.05).

Figure 4. TBR in Different Arterial Regions

Mean of the max TBR in different arterial regions. Error bars indicate ± 1 SD. Max TBRs of the carotid arteries were significantly higher than the max TBRs in any peripheral region (*p < 0.05). CFA = carotid femoral arteries; SFA = superficial femoral arteries; other abbreviation as in Figure 2.

Figure 5. TBRs of Right Versus Left Arterial Regions

Correlations of mean of the max TBR in the right versus left (A) SFA and (B) carotid arteries. Significant, high correlations between right and left arteries in these regions demonstrate the global nature of atherosclerotic inflammation. Abbreviations as in Figures 2 and 4.