) This research application aims to develop a novel, noninvasive method to diagnose and quantify atherosclerosis in patients with cardiovascular diseases. Cardiovascular diseases are responsible for 50% of the deaths in the United States but there is no clinically useful noninvasive method to diagnose the presence of atherosclerosis. The investigators have developed several monoclonal antibodies that immunostain oxidation-specific epitopes that are present within atherosclerotic lesions. These epitopes are present in cells and tissues that contain oxidized LDL and other oxidatively modified proteins. Preliminary data demonstrate that the specific intravenous injection of these radiolabeled antibodies results in specific uptake within atherosclerotic plaques without significant uptake in normal vessel wall. The broad aims of this research application are to evaluate in animal models several candidate antibodies, or antibody fragments, which lead to the optimal uptake within atherosclerotic lesions in rabbits or mice, to develop radioisotopic imaging agents, such as technetium-99m or magnetic resonance agents to noninvasively image atherosclerosis and to eventually apply these methods in patients with atherosclerotic cardiovascular diseases. Dr. Tsimikas has completed his cardiology training and a post-doctoral period in the La Jolla SCOR laboratories of Dr. Joseph Witztum, who will be the mentor for Dr. Tsimikas. The purpose of this application is to obtain funding to allow Dr. Tsimikas to begin his academic career with time necessary to achieve the goals listed. Dr. Tsimikas has already proved the feasibility of this project and needs the protected research time that would be afforded by this Grant to translate this research into clinical studies in man and afford him the opportunity to begin a promising academic career in Cardiology.
