Identifying active vascular micro‐calcification by 18F‐sodium fluoride positron emission tomography
Vesey, A.T. Irkle, A. Skepper, J.N. Bird, Joseph Dweck, M.R. Joshi, F.J. Gallagher, F.A. Warburton, E.A. Bennett, M.R. Brindle, K.M.
Vesey, A.T.
Irkle, A.
Skepper, J.N.
Bird, Joseph
Dweck, M.R.
Joshi, F.J.
Gallagher, F.A.
Warburton, E.A.
Bennett, M.R.
Brindle, K.M.
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2015-07
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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.
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Vesey AT, Irkle A, Lewis DY et al (2015) Identifying active vascular microcalcification by 18F-sodium fluoride positron emission tomography. Atherosclerosis. 241(1): e14.
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