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


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Authors

Irkle, Agnese 
Vesey, Alex T 
Lewis, David Y 
Skepper, Jeremy N 
Bird, Joseph LE 

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.

Description

Keywords

Aged, Atherosclerosis, Carotid Arteries, Female, Fluorine Radioisotopes, Humans, Male, Positron-Emission Tomography, Sodium Fluoride, Vascular Calcification

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

6

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (096823/Z/11/Z)
British Heart Foundation (None)
Cancer Research Uk (None)
British Heart Foundation (None)
Medical Research Council (G1000847)
Cancer Research UK (CB4100)
Cancer Research UK (C14303/A17197)
Cancer Research Uk (None)
Medical Research Council (G0800784)
British Heart Foundation (None)
British Heart Foundation (None)
AI Wellcome Trust PhD Programme in Metabolic and Cardiovascular Disease Grant Number 096823/Z/11/Z, Wellcome Trust (WT103782AIA), British Heart Foundation (RG/10/007/28300, CH/09/002/26360, PG/12/8/29371), NHS Research Scotland and NIHR Cambridge Biomedical Research Centre.