Identifying active vascular micro‐calcification by 18F‐sodium fluoride positron emission tomography

Abstract

Background: Vascular calcification is an active cell-mediated process that is a hallmark of atherosclerosis. Whilst macro-calcification confers stability to plaque, micro-calcification is a key feature of high-risk atheroma associated with major adverse cardiovascular events. Positron emission tomography combined with computed tomography (PET/CT) imaging of atherosclerosis using 18F-sodium fluoride (18F-NaF) has the potential to identify active micro-calcification and thus high-risk plaque. The precise molecular mechanism of 18F-NaF binding has however not been validated. The aim of this study was to provide a comprehensive model describing the binding characteristics, pharmacodynamics and pharmacokinetics of 18F-NaF.

Methods: Patients undergoing carotid endarterectomy were studied. 18F-NaF binding was analysed using a combination of electron microscopy, autoradiography, gamma scintigraphy, histology and immunohistochemistry, pre-clinical microPET/microCT and dynamic clinical PET/CT.

Results: 18F-NaF was shown to bind to calcium within plaque with high affinity. Binding was selective and specific. 18F-NaF PET was able to identify on-going nascent micro-calcification far beyond the resolution of clinical and pre-clinical CT systems. Furthermore, 18F-NaF was able to distinguish between areas of macro and micro-calcification.

Conclusions: 18F-NaF PET/CT is the only currently available clinical imaging platform that can detect micro-calcification in active unstable atherosclerosis. The use of 18F-NaF will foster new approaches to developing treatments targeting unstable plaque and vascular calcification.