IMAGING ATHEROSCLEROSIS WITH SPECIFIC ANTIBODIES

使用特异性抗体对动脉粥样硬化进行成像

• 批准号: 2838869
• 负责人: SOTIRIOS TSIMIKAS
• 金额: $ 10.64万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-15 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2838869
• 关键词: angiography; atherosclerosis; atherosclerotic plaque; bioimaging /biomedical imaging; cardiovascular disorder diagnosis; contrast media; diagnosis design /evaluation; immunocytochemistry; laboratory mouse; laboratory rabbit; low density lipoprotein; method development; monoclonal antibody; noninvasive diagnosis; radiotracer

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)

描述 （改编自申请人的摘要）本研究申请的目的是 开发一种新颖的无创方法来诊断和量化动脉粥样硬化 心血管疾病的患者。 心血管疾病是 负责美国50％的死亡，但没有 临床上有用的无创方法来诊断存在 动脉粥样硬化。 研究人员已经开发了几个单克隆 免疫抑制剂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中，并且 含有氧化的LDL和其他氧化蛋白质的组织。 初步数据表明，特定的静脉注射 这些放射性标记的抗体会导致特定的吸收 正常容器壁中没有明显吸收的动脉粥样硬化斑块。 该研究申请的广泛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 在兔或小鼠的动脉粥样硬化病变中的最佳摄取，以发展 放射性化成像剂，例如Technetium-99m或磁共振 非侵袭性的药物形象性动脉粥样硬化，并最终应用这些 动脉粥样硬化心血管疾病患者的方法。 Tsimikas博士已经完成了他的心脏病学培训和博士后培训 约瑟夫·维茨图姆（Joseph Witztum Tsimikas博士的导师。 本申请的目的是获得 资金允许Tsimikas博士随着时间的流逝开始他的学术生涯 实现列出的目标所必需的。 Tsimikas博士已经证明了 该项目的可行性，需要受保护的研究时间 这笔赠款可以将这项研究转化为临床研究 在人中，让他有机会开始有前途的学术生涯 在心脏病学中。 （抽象的结尾）