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

• Published in: Nature communications 2015-07, Vol.6, p.7495-7495
• Main Authors: Irkle, Agnese, Vesey, Alex T, Lewis, David Y, Skepper, Jeremy N, Bird, Joseph L E, Dweck, Marc R, Joshi, Francis R, Gallagher, Ferdia A, Warburton, Elizabeth A, Bennett, Martin R, Brindle, Kevin M, Newby, David E, Rudd, James H, Davenport, Anthony P
• Format: Article
• Language: English
• Subjects: Aged; Atherosclerosis - diagnosis; Atherosclerosis - pathology; Carotid Arteries - pathology; Female; Fluorine Radioisotopes; Humans; Male; Positron-Emission Tomography - methods; Sodium Fluoride - chemistry; Vascular Calcification - diagnosis
• ISSN: 2041-1723
• DOI: 10.1038/ncomms8495

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 (18)F-sodium fluoride ((18)F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of (18)F-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse (18)F-NaF binding. We show that (18)F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. (18)F-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 (18)F-NaF may foster new approaches to developing treatments for vascular calcification.