THROMBUS IMAGING BY RADIOLABELED MONOCLONAL ANTIBODIES

点击翻译按钮获取中文摘要

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.