SCINTIGRAPHIC VISUALIZATION OF PULMONARY THROMBI WITH I-123 YPACK-TNK-TPA

Background: We have previously demonstrated that radiolabeled tissue-t ype plasminogen activator (tPA) in which the plasminogen-activating ca talytic site has been inactivated binds avidly to thrombi and can be u sed for scintigraphic detection of pulmonary thrombi in vivo. The pres ent study was performed to overcome identified limitations of the init ially developed approach and to determine whether a tracer made with a molecular variant of tPA, TNK-tPA, would provide superior images of p ulmonary thrombi and hence facilitate differential diagnosis of pulmon ary embolism from acute myocardial infarction. It was thought that TNK -tPA may be superior in view of its longer biological half-life and le ss avid uptake by macrophages that would otherwise contribute to high background because of non-clot-selective(1) uptake of the tracer. Meth ods: I-123-tyrosylprolylarginyl chloromethyl ketone (I-123-YPACK-TNK-t PA) was infused into the systemic circulation of dogs with either pulm onary or right ventricular thrombi induced with thrombogenic tips of m odified guide wires. Planar and single-photon emission computed tomogr aphy (SPECT) scintigraphic data were obtained, and blood and tissue sa mples were acquired for analysis of the distribution of the radiotrace r over time. Results: Tracer cleared from blood with an a phase half-l ife of 10+/-1 min, paralleling the clearance of unlabeled TNK-tPA. Onl y minimal release of labeled fragments from liver into blood occurred during the entire time course of the imaging studies. Pulmonary thromb i were visualized with SPECT within 30-120 min in all dogs. Images wer e superior to those obtained after infusion of labeled wild-type tPA, primarily because of diminished background radioactivity and consequen tly increased scintigraphic contrast. In one dog which had a right ven tricular thrombus, the thrombus was readily detectable in both planar and SPECT images. Conclusions: Radiolabeled TNK-tPA in which plasminog en-activating activity has been inhibited biochemically is an excellen t radiopharmaceutical for prompt scintigraphic detection of pulmonary and ventricular thrombi in vivo, and an attractive candidate for rapid , sensitive and non-invasive diagnosis of pulmonary thromboembolic dis ease in patients.