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.
- positron emission tomography
- computed tomography
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Contributors Each author has contributed significantly to the submitted work. DEN, MRD, WJ, AMF, CL, EJRvB and JR undertook the conception and design of the study, and the analysis and interpretation of the data was undertaken by WJ, ATV, AN, CM, MC, AV and SM. The drafting of the manuscript and its revision was completed by WSAJ, MRD and DEN. Each has read and approved the manuscript as written, and there are no conflicts of interest to disclose. None of the paper’s contents have been published previously and it is not under consideration elsewhere. Sadly, our coauthor Martin Connell has died but we wish to include him posthumously in our manuscript.
Funding The study and MRD, WJ and DEN are supported by the British Heart Foundation (FS/12/84, FS/10/026, CH/09/002, RG/16/10/32375, RM/13/2/30158, RE/13/3/30183). DEN is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). MRD is the recipient of the Sir Jules Thorn Award for Biomedical Research 15/JTA. JHFR is part-supported by the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation and the Wellcome Trust. The Wellcome Trust Clinical Research Facility and Clinical Research Imaging Centre are supported by NHS Research Scotland (NRS) through NHS Lothian.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval This study was approved by the local research ethics committee.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request.
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