In vivo alpha-V beta-3 integrin expression in human aortic atherosclerosis
| العنوان: | In vivo alpha-V beta-3 integrin expression in human aortic atherosclerosis |
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| 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, Rudd, James Hf, Newby, David E, Dweck, Marc R |
| المساهمون: | Jenkins, William S [0000-0001-8872-0413], Rudd, James Hf [0000-0003-2243-3117], Apollo - University of Cambridge Repository |
| المصدر: | Jenkins, W S, Vesey, A T, Vickers, A, Neale, A, Moles, C, Connell, M, Joshi, N V, Lucatelli, C, Fletcher, A M, Spratt, J C, Mirsadraee, S, van Beek, E JR, Rudd, J H F, Newby, D E & Dweck, M R 2019, ' In Vivo Alpha-V Beta-3 Integrin Expression in Human Aortic Atherosclerosis ', Heart, vol. 105, no. 24, pp. 1868–1875 . https://doi.org/10.1136/heartjnl-2019-315103Test Heart |
| بيانات النشر: | BMJ, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Cardiac & Cardiovascular Systems, positron emission tomography, PET/CT, integrin, Aortic Diseases, Carboxylic Acids, Myocardial Infarction, Aorta, Thoracic, 18F-SODIUM FLUORIDE UPTAKE, Polyethylene Glycols, POSITRON-EMISSION-TOMOGRAPHY, Positron Emission Tomography Computed Tomography, Image Interpretation, Computer-Assisted, Humans, Carotid Stenosis, Vascular Calcification, 1102 Cardiorespiratory Medicine and Haematology, ALPHA(V)BETA(3), Aged, F-18-AH111585, Inflammation, Science & Technology, 1103 Clinical Sciences, computed tomography, Aortic and Vascular Disease, Integrin alphaV, Middle Aged, Atherosclerosis, Integrin alphaVbeta3, CALCIFICATION, MYOCARDIAL-INFARCTION, Cardiovascular System & Hematology, MARKER, Positron-Emission Tomography, Cardiovascular System & Cardiology, Female, Radiopharmaceuticals, Peptides, Life Sciences & Biomedicine, Cyclobutanes |
| الوصف: | 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.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. |
| وصف الملف: | application/pdf |
| تدمد: | 1468-201X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e28326ff7a9a63011f4ba80ab006af16Test https://www.repository.cam.ac.uk/handle/1810/294865Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e28326ff7a9a63011f4ba80ab006af16 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1468201X |
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