Detection of vulnerable atherosclerotic plaque with a novel 18F-labeled Integrin targeted PET imaging agent

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ABSTRACT Myocardial infarction and stroke are major causes of morbidity and mortality among patients with cardiovascular disease and a major cause of long-term disability in the United States. Current imaging techniques are primarily used to determine the severity of luminal stenosis resulting from carotid plaque; however, stroke and transient ischemic attack (TIA) are often associated with the rupture of plaques from regions with non-significant luminal stenosis. Accurate identification of these high-risk, rupture-prone plaques may potentially prevent stroke, TIA and myocardial infarction in a significant number of patients. Non-contrast CT and CT angiography (CTA) are capable of quantifying calcium burden, plaque ulceration, and presence of lipid; however, CT uses ionizing radiation and cannot provide further information regarding risk of plaque rupture. Magnetic resonance imaging and angiography (MRI-MRA) can be used for assessment of plaque composition. However, MRI is technically difficult which prevents its large scale implementation for routine clinical use. There is an unmet clinical need for a non- invasive imaging test to accurately identify carotid plaques which are likely to rupture. Our team is developing a noninvasive test for identification of vulnerable plaque with the use of a new 18F labeled compound that can be detected with positron emission tomography (PET) imaging. This tracer has been shown to bind to integrin molecules found on the cell surface of macrophages, smooth muscle cells and endothelial cells, all of which are found in great abundance in vulnerable plaque. As a first step towards using this agent for clinical applications, we propose to demonstrate that carotid plaque uptake of this compound is increased in vulnerable plaque in patients who have had a recent stroke or TIA relative to patients with stable carotid artery plaque who are free of stroke or TIA. Our goal is to develop a noninvasive imaging test that can predict which carotid plaque is vulnerable and at an increased risk of rupture. This will enable physicians to prevent stroke or TIA in these patients by removal of plaque by surgery or carotid artery stenting. Ultimately, this technology may be used to detect vulnerable plaque in other vascular beds including the coronary arteries.