VISUALIZATION OF THROMBI IN PULMONARY-ARTERIES WITH RADIOLABELED, ENZYMATICALLY INACTIVATED TISSUE-TYPE PLASMINOGEN-ACTIVATOR

Background Despite the high frequency of pulmonary thromboembolism and its significant morbidity and mortality, diagnosis remains suboptimal . We have been developing a method for prompt detection with the use o f radiolabeled, inactivated tissue-type plasminogen activator (TPA) an d performed the present study to determine whether its use permits rap id scintigraphic visualization of pulmonary thrombi in vivo. Methods a nd Results The thrombolytic, but not fibrin-binding, property of TPA w as inactivated with a tripeptide chloromethyl ketone (YPACK) that had already been iodinated with I-123 to radiolabel the TPA. Pulmonary art erial thrombosis was induced in nine dogs with the use of guide wires modified to provide thrombogenic tips. I-123-YPACK-TPA (1.1 to 7.8 mCi , 0.5 to 7.8 mg) was infused for 5 minutes into either the systemic or the pulmonary circulation. Clearance of radioactivity from the blood was rapid and indistinguishable from that of unlabeled, thrombolytical ly active TPA, with only 6.7+/-1.0% (mean+/-SEM) of peak radioactivity remaining after 60 minutes and minimal release of labeled fragments f rom the liver during this interval. Thrombi were visualized with singl e photon emission computed tomography and/or planar imaging 40 to 120 minutes after infusion of tracer in all seven animals given at least 3 .7 mCi of I-123-YPACK-TPA. Ratios of radioactivity in thrombus (wet ma ss, 610+/-64 mg) to blood were high (14+/-3:1). Conclusions The use of radiolabeled TPA in which thrombolytic activity is inactivated permit s prompt scintigraphic detection of thrombi in pulmonary arteries in v ivo.