Sufficient high affinity plasminogen activator will be isolated from blood to enable its effect on fibrinogen degradation to be studied. This will include a study of the plama factor which we have identified but not characterized which increases the activity of the plasminogen activator of blood. The hypothesis that conversion of proactivator to activator requires some clotting activity will be tested. The effect of fibrin and fibrinogen on plasmin elaboration by the high affinity plasminogen activator of blood will be tested using a specific fluorescent substrate. Since blood is a relatively poor source of plasminogen activator, other sources such as tissue and cadaver perfusates will be used to isolate sufficient quantity of high affinity activator for radiolabeling. Iodination by chloromine-T will be the initial method used for attaching I125 to the activator. Studies in animals in whom pulmonary emboli have been induced will be undertaken in order to evaluate the in vivo properties of a high affinity activator as a diagnostic and therapeutic agent. Localization by scanning as well as lysis will be compared with that of radiolabeled urokinase.
