THE OBJECTIVE OF THIS RESEARCH IS THE DEVELOPMENT OF A DIAGNOSTIC METHOD FOR THE DETECTION OF DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM.

THE OBJECTIVE OF THIS RESEARCH IS THE DEVELOPMENT OF A DIAGNOSTIC METHOD FOR THE DETECTION OF DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM. THESE CONDITIONS OCCUR IN OVER ONE MILLION PEOPLE PER YEAR IN THE U.S. AND ARE A LEADING CAUSE OF DEATH. THE APPROACH WILL BE TO TAKE ADVANTAGE OF THE VERY HIGH SPECIFICITY THAT TISSUE PLASMINOGEN ACTIVATOR (T-PA) HAS FOR FIBRIN, A MAJOR COMPONENT OF CLOTS. WHEN T-PA IS INTRODUCED INTO THE CIRCULATION, IT LOCALIZES AT THECLOT. IF THAT T-PA MOLECULE HAS BEEN LABELED WITH A RADIO- CHEMICAL, THEN IT WILL BE POSSIBLE TO DETECT THE PRESENCE OFTHE CLOT AND TO IMAGE IT. IN PHASE I, THIS CONCEPT WILL BE TESTED BY PREPARING LABELED T-PA AND CONFIRMING THAT IT RETAINS ITS FIBRIN-BINDING PROPERTIES. NEXT, THE LABELED T-PA WILL BE INJECTED INTO ANIMALS WITH CLOTS IN THE JUGULARVEIN. THE TISSUE DISTRIBUTION OF THE T-PA WILL THEN BE DETERMINED. FINALLY, THE EFFECT OF INACTIVATING THE ENZYME,REMOVING THE CARBOHYDRATE, AND FRAGMENTATION OF T-PA ON ITS BINDING TO FIBRIN WILL BE DETERMINED. THIS MAY ENABLE A MOLECULE TO BE ENGINEERED THAT HAS EVEN MORE DESIRABLE PROPERTIES THAN THE NATURAL T-PA.