Identifying active vascular microcalcification by 18F-sodium fluoride positron emission tomography

Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of high-risk atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using F-18-sodium fluoride (F-18-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of F-18-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse F-18-NaF binding. We show that F-18-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. F-18-NaF PET/CT imaging can distinguish between areas of macro-and microcalcification. This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis. The use of F-18-NaF may foster new approaches to developing treatments for vascular calcification.