IMAGING ATHEROSCLEROSIS WITH SPECIFIC ANTIBODIES

描述 （摘自申请人摘要）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 在心血管疾病患者中。 心血管疾病是 造成了美国50%的死亡， 临床上有用的非侵入性方法来诊断存在的 动脉粥样硬化 研究人员已经开发出几种单克隆抗体， 免疫染色存在的氧化特异性表位的抗体 动脉粥样硬化病变中。 这些表位存在于细胞中， 含有氧化LDL和其他氧化修饰蛋白质的组织。 初步数据表明，特异性静脉注射 这些放射性标记的抗体导致 动脉粥样硬化斑块在正常血管壁中没有显著摄取。 本研究应用的广泛目的是在动物模型中进行评价 几种候选抗体或抗体片段，其导致 在兔或小鼠的动脉粥样硬化病变内的最佳摄取， 放射性同位素成像剂，例如锝-99m或磁共振成像剂， 非侵入性成像动脉粥样硬化的试剂，并最终应用这些试剂， 方法在动脉粥样硬化性心血管疾病患者中。 博士Tsimikas已经完成了心脏病学培训和博士后研究， 在拉霍亚SCOR实验室的约瑟夫·维茨图姆博士，谁将是 齐米卡斯博士的导师 本申请旨在取得 资金，使齐米卡斯博士开始他的学术生涯与时间 实现所列目标所必需的。 齐米卡斯博士已经证明了 该项目的可行性，需要保护的研究时间， 将这项研究转化为临床研究 让他有机会开始一个有前途的学术生涯 在心脏病学。 (End摘要）

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)