دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: In vivo alpha-V beta-3 integrin expression in human aortic atherosclerosis
المؤلفون: Jenkins, William S, Vesey, Alex T, Vickers, Anna, Neale, Anoushka, Moles, Catriona, Connell, Martin, Joshi, Nikhil Vilas, Lucatelli, Christophe, Fletcher, Alison M, Spratt, James C, Mirsadraee, Saeed, van Beek, Edwin JR, Rudd, James HF, Newby, David E, Dweck, Marc R
المساهمون: British Heart Foundation, Wellcome Trust, Sir Jules Thorn Charitable Trust
المصدر: Heart ; volume 105, issue 24, page 1868-1875 ; ISSN 1355-6037 1468-201X
بيانات النشر: BMJ
سنة النشر: 2019
الوصف: Objectives Intraplaque angiogenesis and inflammation are key promoters of atherosclerosis and are mediated by the alpha-V beta-3 (α v β 3 ) integrin pathway. We investigated the applicability of the α v β 3 -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 (TBR max ). Aortic atherosclerotic burden was quantified by CT wall thickness, plaque volume and calcium scoring. Results 18F-Fluciclatide uptake co-localised with regions of increased α v β 3 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 (TBR max 1.29 vs 1.21, p=0.02). Conclusions In vivo expression of α v β 3 integrin in human aortic atheroma is associated with plaque burden and is increased in patients with recent myocardial infarction. Quantification of α v β 3 integrin expression with 18F-fluciclatide PET has potential to assess plaque vulnerability and disease activity in atherosclerosis.
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1136/heartjnl-2019-315103
الإتاحة: https://doi.org/10.1136/heartjnl-2019-315103Test
رقم الانضمام: edsbas.11B3E47E
قاعدة البيانات: BASE