Research Project
3500749
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/year in the USA 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 which is a major component of clots. When t-PA is introduced into the circulation, it localizes at the clot. If that t-PA molecule has been labeled with a radiochemical, then it will be possible to detect the presence of the clot and to image it. In the first phase, we will test the concept by preparing labelled t-PA and confirming that it retains its fibrin-binding properties. Next, the labelled t-PA will be injected into animals in which clots have been formed in the jugular vein. The tissue distribution of the t-PA will then be determined. Finally, the effect of inactivating the enzymatic activity, 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.
