Divergent determinants of 18F–NaF uptake and visible calcium deposition in large arteries: relationship with Framingham risk score

Abstract

To compare regional vascular distribution and biological determinants of visible calcium load, as assessed by computed tomography, as well as of molecular calcium deposition as assessed by (18)F-NaF positron emission tomography. Eighty oncologic patients undergoing (18)F-NaF PET/CT scan were included in the study. Cardiovascular-risk stratification was performed according to a simplified version of the Framingham model [including age, diabetes, smoking, systolic blood pressure and body mass index (BMI)]. Arterial (18)F-NaF uptake was measured by drawing regions of interest comprising the arteries on each slice of the transaxial PET/CT and normalized to blood (18)F-NaF activity to obtain the arterial target-to-background ratio (TBR). The degree of arterial calcification (AC) was measured using a software program providing Agatston-like scores. Differences in mean values and regression analysis were tested. Predictors of AC and TBR were evaluated by univariate and multivariate analysis. p value of 0.05 was considered statistically significant. No correlation was documented between regional calcium load and regional TBR in any of the studied arterial segments. Visible calcium deposition was found to be dependent upon age while it was not influenced by all the remaining determinants of cardiovascular risk. By contrast, (18)F-NaF uptake was significantly correlated with all descriptors of cardiovascular risk, with the exception of BMI. Vascular (18)F-NaF uptake displays a different regional distribution, as well as different biological predictors, when compared to macroscopic AC. The tight dependency of tracer retention upon ongoing biological determinants of vascular damage suggests that this tool might provide an unexplored window on plaque pathophysiology.

18F-NaF Uptake by Atherosclerotic Plaque on PET/CT Imaging: Inverse Correlation Between Calcification Density and Mineral Metabolic Activity

“…The study included 64 patients with either breast or prostate cancer (14 men and 50 women; mean age, 65.3 6 8.2 y; range, 26-81 y) undergoing 18 F-NaF PET/CT to evaluate for the presence of bone metastases. To be included in the study, the patient had to have at least one calcification in the infrarenal abdominal aorta.…”

“…Calcification was defined as a mural area having a minimum density of 130 HU (14). Patients were excluded from the study if they had a history of vasculitis, autoimmune disease, or systemic inflammatory disease or had received chemotherapy or radiotherapy in the preceding 8 wk, as previously proposed (18). Ongoing or previous statin treatment was a further exclusion criterion to exclude the influence of these drugs on the results (19).…”

“…These studies, however, highlighted a striking discrepancy between PET and CT in imaging plaque. In particular, PET-positive areas almost invariably colocalized with calcification, whereas only a fraction of the calcification showed visible 18 F-NaF uptake (9). Moreover, the fraction of calcification that correlated with tracer uptake varied widely according to the arterial segment studied, being as low as 12% if the average of all calcification sites was considered (9), showing great variability in the coronary district (15), and peaking in the carotid arteries (10).…”

“…However, a calcification score represents only a static picture, not the pathophysiologic behavior of plaque, and may not fully correlate with a patient's clinical status and cardiovascular risk (6)(7)(8). Therefore, in view of the similarities between calcification formation and osteogenesis, functional studies with 18 FNaF PET have been performed to complement the calcification score with functional data on plaque mineral metabolism (9)(10)(11)(12)(13)(14)(15). These studies, however, highlighted a striking discrepancy between PET and CT in imaging plaque.…”

Imaging Cardiovascular Calcification

“…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…”