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In vivo alpha-V beta-3 integrin expression in human aortic atherosclerosis.

Jenkins, WS; Vesey, AT; Vickers, A; Neale, A; Moles, C; Connell, M; Joshi, NV; Lucatelli, C; Fletcher, AM; Spratt, JC; et al. Jenkins, WS; Vesey, AT; Vickers, A; Neale, A; Moles, C; Connell, M; Joshi, NV; Lucatelli, C; Fletcher, AM; Spratt, JC; Mirsadraee, S; van Beek, EJ; Rudd, JH; Newby, DE; Dweck, MR (2019) In vivo alpha-V beta-3 integrin expression in human aortic atherosclerosis. Heart, 105 (24). pp. 1868-1875. ISSN 1468-201X https://doi.org/10.1136/heartjnl-2019-315103
SGUL Authors: Spratt, James

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Abstract

OBJECTIVES: Intraplaque angiogenesis and inflammation are key promoters of atherosclerosis and are mediated by the alpha-V beta-3 (αvβ3) integrin pathway. We investigated the applicability of the αvβ3-integrin receptor-selective positron emission tomography (PET) radiotracer 18F-fluciclatide in assessing human aortic atherosclerosis. METHODS: Vascular 18F-fluciclatide binding was evaluated using ex vivo analysis of carotid endarterectomy samples with autoradiography and immunohistochemistry, and in vivo kinetic modelling following radiotracer administration. Forty-six subjects with a spectrum of atherosclerotic disease categorised as stable (n=27) or unstable (n=19; recent myocardial infarction) underwent PET and CT imaging of the thorax after administration of 229 (IQR 217-237) MBq 18F-fluciclatide. Thoracic aortic 18F-fluciclatide uptake was quantified on fused PET-CT images and corrected for blood-pool activity using the maximum tissue-to-background ratio (TBRmax). Aortic atherosclerotic burden was quantified by CT wall thickness, plaque volume and calcium scoring. RESULTS: 18F-Fluciclatide uptake co-localised with regions of increased αvβ3 integrin expression, and markers of inflammation and angiogenesis. 18F-Fluciclatide vascular uptake was confirmed in vivo using kinetic modelling, and on static imaging correlated with measures of aortic atherosclerotic burden: wall thickness (r=0.57, p=0.001), total plaque volume (r=0.56, p=0.001) and aortic CT calcium score (r=0.37, p=0.01). Patients with recent myocardial infarction had greater aortic 18F-fluciclatide uptake than those with stable disease (TBRmax 1.29 vs 1.21, p=0.02). CONCLUSIONS: In vivo expression of αvβ3 integrin in human aortic atheroma is associated with plaque burden and is increased in patients with recent myocardial infarction. Quantification of αvβ3 integrin expression with 18F-fluciclatide PET has potential to assess plaque vulnerability and disease activity in atherosclerosis.

Item Type: Article
Additional Information: © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
Keywords: atherosclerosis, computed tomography, integrin, positron emission tomography, Cardiovascular System & Hematology, 1102 Cardiorespiratory Medicine and Haematology
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Heart
ISSN: 1468-201X
Language: eng
Dates:
DateEvent
29 November 2019Published
17 August 2019Published Online
17 July 2019Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
WT103782AIAWellcome Trusthttp://dx.doi.org/10.13039/100004440
FS/12/29/29463British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
PG/09/083/27667British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
RG/16/10/32375British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
FS/10/026British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
CH/09/002British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
RM/13/2/30158British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
RE/13/3/30183British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
15/JTASir Jules Thorn TrustUNSPECIFIED
PubMed ID: 31422361
Web of Science ID: WOS:000503800100007
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/111777
Publisher's version: https://doi.org/10.1136/heartjnl-2019-315103

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