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

Agnese Irkle, Alex T. Vesey, David Y. Lewis, Jeremy N. Skepper, Joseph L. E. Bird, Marc R. Dweck, Francis R. Joshi, Ferdia A. Gallagher, Elizabeth A. Warburton, Martin R. Bennett, Kevin M. Brindle, David E. Newby, James H. Rudd and Anthony P. Davenport ()
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Agnese Irkle: University of Cambridge
Alex T. Vesey: Centre for Cardiovascular Science, University of Edinburgh
David Y. Lewis: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre
Jeremy N. Skepper: Development and Neuroscience, Multi-Imaging Centre, University of Cambridge
Joseph L. E. Bird: University of Cambridge
Marc R. Dweck: Centre for Cardiovascular Science, University of Edinburgh
Francis R. Joshi: University of Cambridge
Ferdia A. Gallagher: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre
Elizabeth A. Warburton: University of Cambridge
Martin R. Bennett: University of Cambridge
Kevin M. Brindle: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre
David E. Newby: Centre for Cardiovascular Science, University of Edinburgh
James H. Rudd: University of Cambridge
Anthony P. Davenport: University of Cambridge

Nature Communications, 2015, vol. 6, issue 1, 1-11

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

Date: 2015
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DOI: 10.1038/ncomms8495

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