THROMBUS IMAGING BY RADIOLABELED MONOCLONAL ANTIBODIES

冠状动脉血栓形成是临床不稳定的主要原因。 急性心肌梗死患者心肌梗死的发生和发展 不稳定型心绞痛。冠状动脉介入治疗成功后的患者 急性心肌梗死、残余血栓的溶栓治疗 可能是导致重新开放的冠状动脉闭塞的原因。 经皮冠状动脉腔内成形术后的患者 血管成形术(PTCA)，冠状动脉血栓形成可能 造成再狭窄的原因目前尚无准确的成像方法 冠状动脉血栓。 该提案的总体目标是开发和验证 (实验和临床)和临床应用 一种用于冠状动脉血栓即时成像的方法 冠脉内注射~(99m)Tm标记抗纤蛋白 单抗(TC-抗纤维蛋白单抗)。这一总体目标 在以下三个部分中进行了阐述： 被测试的有：一、开发和实验验证：1) 抗体的剂量、注射方式和注射后的时间 影响血栓活性，应进行研究，以便 优化成像协议。2)在控制条件下， 如果不进行溶栓治疗，血栓会逐渐活跃 会因为内在的溶栓作用而下降。此信息是 作为测试另一个特定目标的“基线”是必要的 溶栓治疗后血栓活动性是否发生改变 可以用来评估治疗效果。3)范围内的小血栓 亚毫克到几毫克的体重可能会成功 使用这种技术进行可视化。4)新鲜的和24小时的 血栓可用Tc-抗纤维蛋白单抗检测，因为纤维蛋白是 在两种情况下都存在。II.临床验证：在此 部分，我们计划验证冠状动脉内TC-的方法。 抗纤维蛋白单抗成像，已经在第一部分中进行了优化， 影像与直接影像对比的临床设置 冠状动脉内窥镜下冠状动脉血栓的可视化。 冠脉镜检查是最先进的金标准 血管内血栓的评估。三、临床 应用：在这一节中，冠脉内的TC-抗纤蛋白 单抗将作为冠状动脉造影术的辅助手段 评价冠心病患者溶栓治疗的患病率和疗效 不稳定型心绞痛患者的血栓 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.