RT Journal Article
SR Electronic
T1 In vivo alpha-V beta-3 integrin expression in human aortic atherosclerosis
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP 1868
OP 1875
DO 10.1136/heartjnl-2019-315103
VO 105
IS 24
A1 William S Jenkins
A1 Alex T Vesey
A1 Anna Vickers
A1 Anoushka Neale
A1 Catriona Moles
A1 Martin Connell
A1 Nikhil Vilas Joshi
A1 Christophe Lucatelli
A1 Alison M Fletcher
A1 James C Spratt
A1 Saeed Mirsadraee
A1 Edwin JR van Beek
A1 James HF Rudd
A1 David E Newby
A1 Marc R Dweck
YR 2019
UL http://heart.bmj.com/content/105/24/1868.abstract
AB 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.