Venous thrombosis and pulmonary embolism are major causes of morbidity and mortality. Present diagnostic techniques for these are either inaccurate or invasive. Accurate diagnosis is necessary, however, since current therapy is associated with complications leading to morbidity and mortality. The proposed research aims to understand the behavior of venous thrombi and pulmonary emboli, and to design a specific imaging agent for them. Using a canine model of stasis thrombosis and pulmonary emboilism developed by us, substances with promise as embolus-localizing agents will be labelled with radionuclides and evaluated (by in vivo imaging and post-mortem, in vitro counting) for target/background ratios. Substances will include 99mTc-heat damaged erythrocytes (RBC), 123I fibrinogen fragment E1, 123I fragment dimer-D, 123I soluble fibrin monomer, 99mTc plasmin, 123I factor XIII and 111In oxine. For any agent(s) giving good initial results, we will evaluate the effects of thrombus age, embolus age and herparin. Concurrently, a series of experiments will be performed in which labelled cells and proteins will be incorporated into thrombi and emboli (111In RBC, 113mIn platelets, 131I fibrinogen) and administered intravenously (99mTc RBC, 111In platelets, 123I fibrinogen). Each experiment will use one class of agent (e.g. 111In RBC/99mTc RBC). The rate of gain and loss of each type of activity can be measured and biological halftimes calculated. This will provide an index of thrombolysis and thromboneogenesis which will be used to evaluate methods of experimental thrombus production, species differences, and the effects of herparin and streptokinase on thrombi and emboli.
