Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography

Study Overview
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Brief Summary
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This VISION study aims to investigate the role of inflammation in atherosclerosis using 68Ga- DOTATATE PET, and to validate 68Ga-DOTATATE PET imaging for the detection and quantification of vascular inflammation in the aorta, coronary and carotid arteries. This study will test the hypothesis that in subjects undergoing carotid endarterectomy for symptomatic plaques, there will be a positive correlation between carotid artery 68Ga-DOTATATE PET signal and the underlying degree of carotid inflammation measured by immunohistochemical analysis.

Detailed Description
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Clinical events in atherosclerosis are largely driven by inflammation. Molecular imaging of atherosclerosis can potentially identify high-risk lesions, help guide treatment and illuminate the underlying biology of the disease. 18F-fluorodeoxyglucose (18F-FDG) PET is the gold-standard nuclear molecular imaging technique with well-established roles in atherosclerosis imaging. However, the arterial 18F-FDG signal is non-specific, although it is related to increased macrophage activity with contributions from hypoxia and angiogenesis. Coronary artery imaging with 18F-FDG is particularly difficult, mainly due to high background myocardial cell 18F-FDG uptake, which obscures interpretation of the coronary signal. Efforts to suppress myocardial 18F-FDG uptake with dietary manipulation are challenging for patients and have limited efficacy. PET tracers currently used in cancer imaging, such as 68Ga-DOTATATE, are potentially more specific for inflammation and also lack myocardial muscle uptake. 68Ga-DOTATATE might therefore be better suited than 18F-FDG for imaging inflammation, particularly within the coronary arteries. The VISION study is a prospective, observational study designed to investigate the biology of plaque inflammation in atherosclerosis, using PET imaging with the somatostatin receptor ligand 68Ga-DOTATATE. 50 subjects with atherosclerosis will undergo sequential PET/CT imaging with 68Ga-DOTATATE and 18F-FDG, along with contrast angiography of the carotid and coronary arteries. Autoradiography and immunohistochemistry of excised carotid plaques will be used to validate the imaging data. If successful, 68Ga-DOTATATE imaging will offer a cheaper, more specific non-invasive measure of inflammation than 18F- FDG, particularly in the coronary arteries. This opens up the possibility of better risk stratification for patients with atherosclerosis and could provide a non-invasive platform to test the effects of novel anti-atherosclerosis drugs.

Official Title
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The Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography Study

Conditions
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Atherosclerosis, Stroke, Transient Ischemic Attack, Chronic Stable Angina, Acute Coronary Syndrome

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥40 years of age Can provide written, fully informed consent Have had a transient ischemic attack (TIA) or stroke within the preceding four weeks due to carotid artery atherosclerosis; or have ≥30% carotid artery or epicardial coronary artery stenosis Exclusion Criteria: Renal impairment (eGFR<30mls/min) History of contrast nephropathy Atrial fibrillation Any condition, in the opinion of the investigator, which prevents the participant from lying flat during scanning Women of childbearing potential Inability to provide written informed consent Haemorrhagic stroke within 3 months of study entry Total occlusion of a culprit carotid artery Any medical condition, vital sign or laboratory value that, in the opinion of the investigator, makes the subject ineligible for inclusion

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Carotid artery disease<br>Participants with symptomatic or asymptomatic carotid artery plaques | |
| Coronary artery disease<br>Participants with stable coronary artery disease or recent acute coronary syndrome | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of 68Ga-DOTATATE PET signal to carotid plaque inflammation | This primary outcome measure is correlation between carotid artery 68Ga-DOTATATE PET signal (TBR) and the underlying degree of carotid inflammation, measured by CD68 immunohistochemistry, in patients undergoing carotid endarterectomy. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of 68Ga-DOTATATE signal between symptomatic and asymptomatic carotid plaques |  | Baseline (<1 month from event) | 
| Correlation of carotid artery and coronary artery 68Ga-DOTATATE uptake |  | Baseline | 
| Correlation of Framingham Cardiovascular Risk Scores to arterial 68Ga-DOTATATE uptake |  | Baseline | 
| Correlation between carotid artery 68Ga-DOTATATE autoradiographic signal and degree of carotid inflammation, measured by CD68 immunohistochemistry |  | Baseline | 
| Comparison of myocardial 68Ga-DOTATATE and 18F-FDG uptake |  | Baseline (2 scans within 1 week) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vascular inflammation, Atherosclerosis, Positron Emission Tomography, Molecular Imaging, 68Ga-DOTATATE