The Identification of In Vivo Angiogenesis and Fibrosis in Aortic Stenosis Using Positron Emission Tomography
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- The mean and maximum standardised uptake values (SUV) of fluciclatide for the myocardium and its correlation with the severity of aortic stenosis determined echocardiographically.
研究概览
简要总结
Angiogenesis and fibrosis lie at the heart of a number of fundamental processes responsible for cardiovascular disease. In this proposal, the investigators intend to build upon a highly successful programme of studies exploring the cardiovascular applications of positron emission tomography. Specifically, the investigators will explore the potential role of a novel radiotracer, 18F-fluciclatide, which is a highly selective ligand for the αvβ3 and αvβ5 integrin receptors that are up regulated during angiogenesis, and tissue fibrosis and remodelling. This tracer has been successfully used to assess angiogenesis in metastatic tumours and its uptake is suppressed by anti-angiogenic therapies. The investigators here propose to describe the pattern of uptake of 18F-fluciclatide in cardiovascular diseases, specifically aortic stenosis and aortic atherosclerosis. The investigators will correlate 18F-fluciclatide uptake with in vivo measures of angiogenesis and fibrosis as well as ex vivo histological characterisation of tissue. If successful, this novel radiotracer could provide an extremely important non-invasive method of assessing in vivo angiogenesis, plaque vulnerability, and tissue remodelling as well as potential applications in developing stem cell therapies.
详细描述
Integrins
Integrins are a group of molecules responsible for intercellular adhesion and signalling. They comprise a superfamily of heterodimeric receptors that are composed of 18 different α and β subunits. In combination, they can generate 24 different receptor subtypes with a range of physiological and pathophysiological functions. The αvβ3 receptor is an integrin that is found at low levels on mature endothelial cells but is markedly up regulated on endothelial cells of actively growing blood vessels. It was previously known as the vitronectin receptor although it was subsequently found to bind many other ligands including fibrinogen, fibronectin, laminin, thrombospondin, von Willebrand factor, and certain collagen subtypes. These features are also seen with the αvβ5 integrin receptor, with both receptors recognising the arginine-glycine-aspartate (RGD) motif present on these ligands.
1.1.2 Role of αvβ3 and αvβ5 Integrins in Cardiovascular Disease
The expression of αvβ3 and αvβ5 receptors is up regulated in a number of diseased states and this has been particularly well characterised in the angiogenesis associated with tumour growth and metastases. However, there are many potential roles for this integrin pathway in cardiovascular disease including myocardial infarction, atherosclerosis, restenosis, aortic stenosis and aneurysm disease that have been relatively unexplored.
1.1.2.1 Aortic Stenosis
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •Atrial fibrillation
- •Hepatic failure (Childs-Pugh grade B or C)
- •Renal failure (estimated glomerular filtration rate <25 mL/min)
- •Women of child-bearing potential
- •Contraindication to magnetic resonance imaging
- •Inability to undergo scanning
- •Ochronosis and those with any form of collagen-vascular disease.
结局指标
主要结局
The mean and maximum standardised uptake values (SUV) of fluciclatide for the myocardium and its correlation with the severity of aortic stenosis determined echocardiographically.
时间窗: 1 - 2 years
The mean and maximum standardised uptake values (SUV) of fluciclatide for the myocardium and its correlation with the volume of myocardial fibrosis on magnetic resonance scanning.
时间窗: 1 - 2 years
次要结局
- The mean and maximum standardised uptake values (SUV) of fluciclatide in concomitant aortic atheroma(1 year)
- The mean and maximum standardised uptake values (SUV) of fluciclatide in the aortic valve in patients with aortic stenosis(1 year)