THROMBUS IMAGING BY RADIOLABELED MONOCLONAL ANTIBODIES

冠状动脉血栓形成在临床不稳定性中起主要作用 心肌梗死的发病率 不稳定型心绞痛 在成功进行冠状动脉造影的患者中 急性心肌梗死溶栓，残余血栓，溶栓治疗 可能是导致冠状动脉闭塞的原因 经皮冠状动脉腔内成形术后患者 冠状动脉成形术（PTCA），冠状动脉血栓形成可能是 导致再狭窄的原因是没有准确的成像方法 冠状动脉血栓 本提案的总体目标是制定和验证 (both实验和临床）和临床应用 用于对冠状动脉血栓进行即时成像的方法 冠状动脉内注射~（99）Tc标记抗纤维蛋白抗体 单克隆抗体（Tc-抗纤维蛋白单克隆抗体）。 这一总体目标范围 在以下三个部分中进行了讨论： 被测试的是：I. 开发和实验验证：1） 抗体剂量、给药方式和注射后时间 影响血栓活性，应进行研究， 优化成像方案 2)在控制条件下， 未经溶栓治疗，血栓逐渐活动， 由于内在的血栓溶解而下降。 该信息 作为另一个具体目标的“基线”， 溶栓治疗后血栓活性的变化 可用于评估治疗。 3)范围内有小血栓 亚毫克到几毫克的重量就可以成功地 使用这种技术进行可视化。 4)新鲜的和24小时前的 血栓可通过Tc-抗纤维蛋白单克隆抗体检测，因为纤维蛋白是 在这两种情况下。 二.临床验证：在此 第节，我们计划验证冠状动脉内Tc- 抗纤维蛋白单克隆抗体成像，已在第一节中优化， 通过图像对比， 通过冠状动脉血管镜观察冠状动脉血栓。 冠状动脉血管镜检查是最先进的黄金标准， 血管内血栓的评价。 三. 临床 应用：在本节中，冠脉内Tc-抗纤维蛋白 MAb将用作冠状动脉造影的辅助， 评估溶栓治疗对冠心病的患病率和影响 不稳定型心绞痛患者血栓，患者 急性心肌梗死溶栓治疗后， PTCA术后患者。

Coronary thrombosis plays a major role in clinical instability and development of myocardial infarction in patients with unstable angina. In patients following successful coronary thrombolysis in acute myocardial infarction, residual thrombus may be responsible for reclusion of the reopened coronary artery. In patients following percutaneous transluminal coronary angioplasty (PTCA), coronary thrombus formation may be responsible for restenosis no accurate method exists for imaging coronary thrombi. The overall objective of this proposal is to develop and validate (both experimentally and clinically) and clinically apply a method for instant imaging of coronary thrombi using intracoronary injection of technetium-99m labelled antifibrin monoclonal antibody (Tc-antifibrin MAb). This overall objective is addressed in the following three sections: The hypothese to be tested are: I. Development and experimental validation: 1) Dose of antibody, mode of delivery, and time after injection affect thrombus activity and should be studied in order to optimize the imaging protocol. 2) Under control conditions, without thrombolytic therapy, thrombus activity gradually declines because of intrinsic thrombolysis. This information is necessary as "baseline" for another specific aim which tests whether a change in thrombus activity after thrombolytic therapy can be used to evaluate therapy. 3) Small thrombi in the range of submilligram to a few milligrams of weight may be successfully visualized using this technique. 4) Both fresh and 24 hour old thrombi may be detected by Tc-antifibrin MAb since fibrin is present in both conditions. II. Clinical validation: In this section, we plan to validate the method of intracoronary Tc- antifibrin MAb imaging, which has been optimized in section I, in the clinical setting by comparison of image to direct visualization of coronary thrombus through a coronary angioscope. Coronary angioscopy is the state-of-the-art gold standard for evaluation of intravascular thrombus. III. Clinical applications: In this section, the intracoronary Tc-antifibrin MAb will be used as an adjunct to coronary arteriography to assess prevalence and effect of thrombolytic therapy on coronary thrombus in patients with unstable angina pectoris, patients following thrombolytic therapy of acute myocardial infarction and patients following PTCA.