Rapid Localization of Indium- 111-Labeled Inhibited Recombinant Tissue Plasminogen Activator in a Rabbit Thrombosis Model

The thrombus localizing properties of indium-111-recom-binant tissue plasminogen activator (l~lln.rt_pA) have been investigated in an effort to achieve prompt and accurate detection of thrombi. Unlike previous studies with rt-PA, the active plasminogen catalytic site was permanently inhibited with peptides of chloromethyl ketone so that the radiotracer binds to fibrin without causing fibrinolysis. Thrombi were created in the extemal jugular vein of 14 male New Zealand white rabbits followed by injection of 11~ln-rt-PA. The agent cleared rapidly in vivo with a half-time of 4.6 min. The thrombus: blood ratio in nonheparin-ized rabbits (n = 7) was 6.39 _+ 0.86. The ratio in heparin-ized rabbits (n = 4) was 3.11 _+ 0.23. Thrombi were clearly visible in the planar images of both groups 1 hr postinjec-tion. The combination of rapid thrombus localization an