IMAGING ATHEROSCLEROSIS WITH SPECIFIC ANTIBODIES

描述 (摘自申请者的摘要)本研究申请旨在 开发一种新的非侵入性方法来诊断和量化动脉粥样硬化 在患有心血管疾病的患者中。心血管疾病是 造成了美国50%的死亡，但没有 临床上有用的非侵入性方法诊断是否存在 动脉硬化。研究人员已经研制出几种单克隆体。 免疫染色存在的氧化特异性表位的抗体 在动脉粥样硬化病变内。这些表位存在于细胞和 含有氧化的低密度脂蛋白和其他氧化修饰蛋白的组织。 初步数据显示，特异度静脉注射 这些放射性标记的抗体导致体内的特异性摄取 正常血管壁无明显摄取的动脉粥样硬化斑块。 这项研究应用的主要目的是在动物模型中进行评估 几种候选抗体或抗体片段，导致 兔或小鼠动脉粥样硬化病变的最佳摄取，以发展 放射性同位素显像剂，如~(99)Tm或磁共振 无创成像动脉粥样硬化的试剂，并最终应用于 方法对动脉粥样硬化性心血管疾病患者进行研究。 Tsimikas博士已经完成了他的心脏病学培训和博士后 约瑟夫·维茨塔姆博士在La Jolla SCOR实验室的一段时间，他将成为 Tsimikas博士的导师。此应用程序的目的是获得 资金让Tsimikas博士随着时间的推移开始他的学术生涯 为实现所列目标所必需的。Tsimikas博士已经证明了 该项目的可行性，并需要受保护的研究时间， 由这笔赠款提供，将这项研究转化为临床研究 并为他提供了开始有前途的学术生涯的机会 在心脏病学。(摘要结束)

DESCRIPTION (Adapted from applicants' abstract) 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. (End of Abstract)