Objectives

This study investigated the use of 18F-NaF and 18F-FDG PET/CT to evaluate carotid atheroma development.
Bilateral carotid artery uptake of both tracers was higher in at-risk patients compared to healthy volunteers.
Uptake correlated with several established atherogenic risk factors.
No significant correlations were found between 18F-NaF and 18F-FDG uptake after adjusting for age and gender.
18F-NaF, but not 18F-FDG, correlated with increased 10-year risk of adverse cardiovascular events (Framingham Risk Score - FRS).
Both tracers were associated with elevated thromboembolic risk (CHA2DS2-VASc score).

Methodology

115 subjects (73 healthy volunteers, 42 at-risk for CVD) underwent 18F-NaF and 18F-FDG PET/CT imaging.
Radiotracer uptake was quantitatively assessed by measuring the average blood-pool-corrected mean standardized uptake value (aSUVmean).
Regions of interest (ROIs) were manually delineated on fused PET/CT axial images surrounding the outer perimeter of the left and right common carotid arteries (LCC/RCC).
Blood 18F-NaF and 18F-FDG activity were determined by measuring a ROI in the inferior vena cava.
Multivariable linear regression was used to adjust for blood activity, injected radiotracer dose, and PET/CT system.
Spearman's rank correlation coefficient was used to assess the correlation between 18F-NaF aSUVmean and 18F-FDG aSUVmean.
Univariate and multivariate linear regression models were used to evaluate relationships between CVD risk factors and carotid 18F-NaF / 18F-FDG aSUVmean.
ANOVA was used to compare tracer uptake among different risk groups (FRS and CHA2DS2-VASc).

Relative to healthy volunteers, at-risk subjects had greater uptake of NaF and FDG (10–22% and 16–27% higher, respectively, in both arteries, p<0.05).
On multivariate regression, NaF aSUVmean correlated with age and BMI (p<0.01), and FDG aSUVmean correlated with BMI (p ≤ 0.01), fibrinogen (p<0.01 in LCC only), and total cholesterol (p=0.02 in RCC only).
NaF aSUVmean increased with elevated 10-year CVD risk (p=0.003 in LCC only); NaF uptake was on average 29.1% higher in the highest risk group compared to the lowest risk group.
NaF and FDG aSUVmean increased with elevated thromboembolic risk in both arteries (p<0.05). Uptake was 18.5-21.8% higher in the highest risk groups.
No correlations between NaF and FDG aSUVmean were observed (p>0.05) after adjusting for age and gender.

The study utilizes a cross-sectional design, limiting the ability to establish causal relationships between tracer uptake and the development of atherosclerosis.
The reliance on FRS and CHA2DS2-VASc scores, which have known limitations in risk prediction, could introduce bias.
The manual segmentation of ROIs may introduce inter-observer variability, although the authors mention using established methods. The use of automated segmentation techniques could improve reproducibility.
The study includes subjects on statin therapy (17/115), which can influence tracer uptake. While subjects who started statins within 3 months were excluded, the long-term effects of statin use are not fully accounted for.
Laterality-specific associations are noted, but the underlying mechanisms are not fully explored. Further investigation into the hemodynamic and metabolic differences between the left and right carotid arteries could provide valuable insights.