In Vivo Imaging of Mineral Deposition in Carotid Plaque Using ¹⁸F-Sodium Fluoride PET/CT: Correlation with Atherogenic Risk Factors

Abstract

The purpose of this study was to correlate 18 F-sodium fluoride accumulation in the common carotid arteries of neurologically asymptomatic patients with cardiovascular risk factors and carotid calcified plaque burden. Methods: Two hundred sixtynine oncologic patients were examined by 18 F-sodium fluoride PET/CT. Tracer accumulation in the common carotid arteries was analyzed both qualitatively and semiquantitatively by measuring the blood-pool-corrected standardized uptake value (target-to-background ratio) and comparing it with cardiovascular risk factors and calcified plaque burden. Results: 18 Fsodium fluoride uptake was observed at 141 sites in 94 (34.9%) patients. Radiotracer accumulation was colocalized with calcification in all atherosclerotic lesions. 18 F-sodium fluoride uptake was significantly associated with age (P , 0.0001), male sex (P , 0.0001), hypertension (P , 0.002), and hypercholesterolemia (P , 0.05). The presence of calcified plaque correlated significantly with these risk factors but also with diabetes (P , 0.0001), history of smoking (P 5 0.03), and prior cardiovascular events (P , 0.01). There was a highly significant correlation between the presence of 18 F-sodium fluoride uptake and number of present cardiovascular risk factors (r 5 0.30, P , 0.0001). Conclusion: Carotid 18 F-sodium fluoride uptake is a surrogate measure of calcifying carotid plaque, correlates with cardiovascular risk factors, and is more frequent in patients with a high-risk profile for atherothrombotic events but demonstrates a weaker correlation with risk factors than does calcified plaque burden. This study provides a rationale to conduct further prospective studies to determine whether 18 F-sodium fluoride uptake can predict vascular events, or if it may be used to monitor pharmacologic therapy.

Imaging Cardiovascular Calcification

“…Several other studies have reported similar findings and have led to growing support for the use of 18 F‐NaF for imaging the process of microcalcification and visualizing ongoing mineral deposition within the atherosclerotic plaque 64, 99, 100, 101, 102, 103…”

“…Ten‐year Framingham risk scores for CVD and death are related to 18 F‐NaF uptake 64. Other retrospective studies have shown positive correlations between arterial 18 F‐NaF uptake and CVD risk factors, including age, sex, hypertension, hypercholesterolemia, and diabetes mellitus, further supporting the notion that 18 F‐NaF PET imaging may improve CVD risk stratification 98, 100, 101, 102, 104, 111, 112, 113, 114…”

“…In fact, 41% of patients with CACS >1000 had no significant 18 F‐NaF uptake, and often 18 F‐NaF uptake was found in areas adjacent to and remote from existing coronary calcification. In a separate study, visible arterial calcium was not associated with higher 18 F‐NaF uptake, and 18 F‐NaF uptake was similar in the arterial segments with or without visible calcification 100. Further investigation into the relationship between 18 F‐NaF uptake, visible calcification on CT, and the Framingham risk score for CVD showed that 18 F‐NaF uptake was significantly associated with many cardiovascular risk factors, while visible calcification correlated with age but not other determinants of cardiovascular risk 104…”

“…Recently, substantial attention has been given to using 18 F‐NaF to investigate vascular calcification in the coronary arteries,22, 64 the aorta,99 and the carotid arteries,100 and it has rapidly gained acceptance as a useful tool for the investigation of plaque pathobiology.…”

“…The mismatch pattern between CT calcium imaging and 18 F‐NaF PET imaging occurs as a result of the dynamic and complex procession of vascular calcification 100, 101. In the earliest stage of atherosclerosis, inflammation induces the release of several bone‐forming peptides and further promotes the active deposition of hydroxyapatite matrix.…”