In vivo alpha-V beta-3 integrin expression in human aortic atherosclerosis.
Heart
; 105(24): 1868-1875, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31422361
ABSTRACT
OBJECTIVES:
Intraplaque angiogenesis and inflammation are key promoters of atherosclerosis and are mediated by the alpha-V beta-3 (αvß3) integrin pathway. We investigated the applicability of the αvß3-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 αvß3 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 αvß3 integrin in human aortic atheroma is associated with plaque burden and is increased in patients with recent myocardial infarction. Quantification of αvß3 integrin expression with 18F-fluciclatide PET has potential to assess plaque vulnerability and disease activity in atherosclerosis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças da Aorta
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Integrina alfaVbeta3
/
Aterosclerose
Tipo de estudo:
Prognostic_studies
Limite:
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Heart
Assunto da revista:
CARDIOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Reino Unido