Correlation Between Arterial FDG Uptake and Biomarkers in Peripheral Artery Disease

Abstract

OBJECTIVES A prospective, multicenter 18fluorine-fluorodeoxyglucose (18F-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 18F-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 18F-FDG-PET/CT imaging before Silver-Hawk 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 18F-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.

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

“…However, clinical and experimental studies have failed to show a correlation between 18 F-FDG uptake and macrophage content in atherosclerotic lesions. 21, 26 The evidence suggests that the presence of macrophages does not always indicate active inflammation. Recent studies have revealed macrophage heterogeneity in atherosclerotic lesions, 27 and approximately 25% of macrophages in coronary atherosclerotic plaques have an antiinflammatory phenotype.…”

Bioenergetic Profiles Diverge During Macrophage Polarization: Implications for the Interpretation of 18F-FDG PET Imaging of Atherosclerosis

“…Early 18 F-FDG–based PET imaging studies showed promising results in both the detection of inflammatory lesions and the response of these lesions to therapeutic interventions (4–8). However, some clinical studies failed to demonstrate a significant association between plaque inflammation and 18 F-FDG uptake (4,9), hindering the translation of experimental studies to the clinical practice. Additionally, a direct association between increased glucose uptake and specific macrophage functions or activation states has yet to be validated.…”

Molecular imaging of atherosclerotic lesions by positron emission tomography - can it meet the expectations?

“…Thus, an increase in infl ammatory cells in the perivascular adipose tissue, the largest endocrine organ, does not play a role only in atherogenesis, but it may also infl uence imaging results. Simple correlations of FDG uptake with risk factors, including already existing diseases such as metabolic syndrome, diabetes mellitus as well as with certain laboratory markers of atherosclerosis such as CRP [24,25,26], malondialdehyde-modifi ed LDL [27], LDL-cholesterol and leptin [28], and matrix metalloproteinases [29] were not helpful at all. Interestingly, in particular in peripheral arterial disease, there was no correlation between F-18-FDG uptake and various biomarkers, including hsCRP.…”