Distribution and fate of I-131-labeled components of the fibrinolysin system.

IN THE COURSE of assaying the potency of a variety of fibrinolytic enzyme preparations in dogs and monkeys with isotopelabeled fibrin clots, we observed that the fibrinolytie activity disappeared rapidly from the systemic circulation. Dissolution of blood clots was noted to occur long after the disappearance of measurable circulating fibrinolytic activity. These experimental observations were confirmed in extensive clinical studies.^ Rapid disappearance of exogenously administered plasmin was ascribed to (a) complexing of the active enzyme with circulating inhibitors, (b) selective adsorption onto fibrin substrates, (c) passive diffusion from the vascular system to tissue compartments, and (d) catabolism and excretion. To help elucidate the question of the distribution and metabolic disposition of plasmin as well as that of the delayed fibrinolytic effect, methods were sought to label the enzyme with radioactive isotopes. Iodine was selected as the tracer of choice because it is readily incorporated into protein molecules, the labeled protein behaves metabolically in a manner similar to the unlabeled compound, and the degradation products are excreted, rather than reutilized. Since a number of plasminogen preparations activated by different activators were used, the metabolism of individual compo-