| Title: |
In vivo alpha-V beta-3 integrin expression in human aortic atherosclerosis. |
| Authors: |
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 |
| Publisher Information: |
BMJ Publishing Group |
| Publication Year: |
2019 |
| Collection: |
St George's University of London: Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
1468-201X |
| Relation: |
https://openaccess.sgul.ac.uk/id/eprint/111777/1/1868.full.pdf; 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 |
| Availability: |
https://openaccess.sgul.ac.uk/id/eprint/111777/; https://openaccess.sgul.ac.uk/id/eprint/111777/1/1868.full.pdf |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.B1F25BE7 |
| Database: |
BASE |