Abstract 17385: 18 F-Naf - a Specific Marker for Vascular Calcification in Atherosclerosis
Circulation 2013; 128: A17385
Abstract 17385: [18]F-NaF - A Specific Marker for Vascular Calcification in Atherosclerosis
Agnese Irkle1; Joseph L Bird1; Jeremy N Skepper2; Marc R Dweck3; Francis R Joshi4; Alex T Vesey3; Martin Bennett4; David E Newby3; Elizabeth A Warburton5; James H Rudd4; Anthony P Davenport1
1 Clinical Pharmacology Unit, Dept of Medicine, Univ of Cambridge, Cambridge, United Kingdom
2 Multi-Imaging Cntr, Dept. of Physiology, Development and Neuroscience, Univ of Cambridge, Cambridge, United Kingdom
3 Cntr for Cardiovascular Science, Univ of Edinburgh, Edinburgh, United Kingdom
4 Div of Cardiovascular Medicine, Univ of Cambridge, Cambridge, United Kingdom
5 Dept of Clinical Neurosciences, Univ of Cambridge, Cambridge, United Kingdom
Background: Vascular calcification scoring by CT is a predictor of future cardiovascular events. Macro-calcification (>5 μm) is detectable by CT imaging but micro-calcification (<5 μm) is difficult to detect because of size. 18F-NaF is emerging as a new marker of vascular calcification but its exact tissue binding in atherosclerosis is unknown.
We characterized the pharmacodynamics of 18F-NaF binding to ex vivo carotids containing macro- and micro-calcification and correlated binding with histological markers to assess selectivity of 18F-NaF for calcium.
METHODS: Carotid endarterectomy specimens were obtained after IRB approval. X-ray microanalysis was used to measure the ratio of calcium to fluoride binding after incubation with NaF. Ligand binding assays used a clinically relevant concentration of 10-11M 18F-NaF and 10-11-10-6M was used to construct concentration curves. Calcium was detected in adjacent sections with Alizarin Red, macrophages (CD68), endothelial (CD31) or smooth muscle cells (actin) by IHC.
RESULTS:18F-NaF binding to cryostat sections was linear (n = 5). Once bound to intact plaques, there was a slow exponential decline (7±1% signal decrease in one hour, t1/2=323 min). The amount of fluoride bound to micro-calcification (Ca2+/F-=2.4±0.25 n=10) was significantly higher than macro-calcification (Ca2+/F- 4.8±0.33 n=5). No binding was detected in non-calcified regions of smooth muscle. In agreement, there was a high correlation between 18F-NaF and areas of calcium delineated by Alizarin Red but little correlation with soft tissue markers.
CONCLUSION:18F-NaF is a specific marker of calcification, with signal increasing proportionally to the surface area of calcification and concentration of the ligand. Binding is stable, with a small signal loss over time. Calcified regions do not contain inflammatory cells or neovascularisations. However calcifications are surrounded by active regions of remodelling, which may affect mineral formation.
Author Disclosures: A. Irkle: None. J.L. Bird: None. J.N. Skepper: None. M.R. Dweck: None. F.R. Joshi: None. A.T. Vesey: None. M. Bennett: None. D.E. Newby: None. E.A. Warburton: None. J.H. Rudd: None. A.P. Davenport: None.
Key Words: Arteriosclerosis • Calcium • Carotid arteries • Positron emission tomography • Radioisotopes