Coronary ¹⁸F‑sodium fluoride PET imaging: State-of-the-art technology and translational clinical perspectives

Coronary artery disease remains the leading cause of morbidity and mortality worldwide. Acute coronary events are frequently triggered by biologically active, rupture-prone atherosclerotic plaques that are not reliably identified by conventional anatomical imaging. Although coronary computed tomography angiography (CCTA) provides robust assessments of plaque burden and stenosis severity, it offers limited insight into ongoing biological activity within the plaque microenvironment. ¹⁸F‑sodium fluoride (¹⁸F-NaF)-positron emission tomography (PET) has emerged as a promising molecular imaging modality capable of detecting active microcalcifications, a key biological process associated with plaque vulnerability and rupture. Preclinical and translational studies have established the biological basis of ¹⁸F-NaF uptake, demonstrating preferential binding to newly formed hydroxyapatite deposits that reflect inflammation-driven osteogenic activity within atherosclerotic plaques. Clinical investigations have shown that ¹⁸F-NaF uptake localizes to the culprit lesions in acute myocardial infarction and correlates with high-risk plaque features on CCTA. Quantitative metrics, such as coronary microcalcification activity, enable reproducible whole-heart evaluation of disease activity. Multiple observational and prospective studies have demonstrated that increased ¹⁸F-NaF activity independently predicts myocardial infarction and major adverse cardiovascular events. Recent advances in PET technology, including motion correction algorithms, high-resolution reconstruction, and digital silicone photomultiplier detectors, have substantially improved image quality and reproducibility. This review summarizes the biological rationale, technical considerations, and emerging clinical evidence supporting the use of ¹⁸F-NaF PET for imaging coronary plaque.