Angiogenesis and Fibrosis in Aortic Stenosis

Summary

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.

Conditions

• Aortic Stenosis
• Fibrosis
• Neovascularization, Pathologic

Interventions

PROCEDURE

Cardiac MRI scan

Cardiac MRI scan with assessment of late gadolinium enhancement and T1 mapping.

RADIATION

CT-PET scan

Computed Tomography / Positron Emission Tomography scan with 18F-fluciclatide tracer.

PROCEDURE

Echocardiogram

Echocardiography.

RADIATION

CT-coronary angiogram scan

CT-coronary angiogram following CT-PET scan. Standard protocol.

PROCEDURE

Aortic Valve Replacement

For AVR (already scheduled prior to enrollment)

Sponsors & Collaborators

• University of Edinburgh

  lead OTHER

Principal Investigators

• David E Newby, MBChB PhD · University of Edinburgh

• William Sa Jenkins, MBChB MRCP · University of Edinburgh

Eligibility

Min Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-04-30

Primary Completion

2015-08-31

Completion

2015-08-31

Countries

• United Kingdom

Study Locations