In Vivo Coronary ¹⁸F-Sodium Fluoride Activity: Correlations With Coronary Plaque Histological Vulnerability and Physiological Environment

Background: ¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET)/computed tomography (CT) is a promising new approach for assessing microcalcification in vascular plaque.

Objectives: This prospective study aimed to evaluate the associations between in vivo coronary ¹⁸F-NaF PET/CT activity and ex vivo histological characteristics, to determine whether coronary ¹⁸F-NaF activity is a novel biomarker of plaque pathological vulnerability, and to explore the underlying physiological environment of ¹⁸F-NaF adsorption to vascular microcalcification.

Methods: Patients with coronary artery disease (CAD) underwent coronary computed tomography angiography (CTA) and ¹⁸F-NaF PET/CT. Histological vulnerability and immunohistochemical characteristics were evaluated in coronary endarterectomy (CE) specimens from patients who underwent coronary artery bypass grafting with adjunctive CE. Correlations between in-vivo coronary ¹⁸F-NaF activity with coronary CTA adverse plaque features and with ex vivo CE specimen morphological features, CD68 expression, inflammatory cytokines expression (tumor necrosis factor-α, interleukin-1β), osteogenic differentiation cytokines expression (osteopontin, runt-related transcription factor 2, osteocalcin) were evaluated. High- and low- to medium-risk plaques were defined by standard pathological classification.

Results: A total of 55 specimens were obtained from 42 CAD patients. Coronary ¹⁸F-NaF activity of high-risk specimens was significantly higher than low- to medium-risk specimens (median [25th-75th percentile]: 1.88 [1.41-2.54] vs 1.12 [0.91-1.54]; P < 0.001). Coronary ¹⁸F-NaF activity showed high discriminatory accuracy in identifying high-risk plaque (AUC: 0.80). Coronary CTA adverse plaque features (positive remodeling, low-attenuation plaque, remodeling index), histologically vulnerable features (large necrotic core, thin-fibro cap, microcalcification), CD68 expression, tumor necrosis factor-α expression, and interleukin-1β expression correlated with coronary ¹⁸F-NaF activity (all P < 0.05). No significant association between coronary ¹⁸F-NaF activity and osteogenic differentiation cytokines was found (all P > 0.05).

Conclusions: Coronary ¹⁸F-NaF activity was associated with histological vulnerability, CD68 expression, inflammatory cytokines expression, but not with osteogenic differentiation cytokines expression. ¹⁸F-NaF PET/CT imaging may provide a powerful tool for detecting high-risk coronary plaque and could improve the risk stratification of CAD patients.