title: Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography.
abstract: 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.
authors.affiliation: Division of Experimental Medicine &Immunotherapeutics (EMIT), Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK.
authors.forename: Agnese
authors.initials: A
authors.lastname: Irkle
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
authors.forename: Alex T
authors.identifier: 0000000176813778
authors.initials: AT
authors.lastname: Vesey
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
authors.forename: David Y
authors.initials: DY
authors.lastname: Lewis
authors.affiliation: Department of Physiology, Development and Neuroscience, Multi-Imaging Centre, University of Cambridge, Cambridge, CB2 3EG, UK.
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Skepper
authors.affiliation: Division of Experimental Medicine &Immunotherapeutics (EMIT), Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK.
authors.forename: Joseph L E
authors.initials: JL
authors.lastname: Bird
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Dweck
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK.
authors.forename: Francis R
authors.initials: FR
authors.lastname: Joshi
authors.affiliation: 1] Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK. [2] Department of Radiology, Box 218 Level 5, University of Cambridge, Cambridge, CB2 0QQ, UK.
authors.forename: Ferdia A
authors.initials: FA
authors.lastname: Gallagher
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Warburton
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Bennett
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brindle
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK.
authors.forename: James H
authors.initials: JH
authors.lastname: Rudd
authors.affiliation: Division of Experimental Medicine &Immunotherapeutics (EMIT), Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Davenport
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000175:diagnosis* / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology*; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D012969:Sodium Fluoride / Q000737:chemistry*; D061205:Vascular Calcification / Q000175:diagnosis*
chemical_list: D005462:Fluorine Radioisotopes; D012969:Sodium Fluoride