Scintigraphic visualization of pulmonary thrombi with 123I-YPACK-TNK-tPA.
BACKGROUND
We have previously demonstrated that radiolabeled tissue-type plasminogen activation (tPA) in which the plasminogen-activating catalytic site has been inactivated binds avidly to thrombi and can be used for scintigraphic detection of pulmonary thrombi in vivo. The present study was performed to overcome identified limitations of the initially developed approach and to determine whether a tracer made with a molecular variant of tPA, TNK-tPA, would provide superior images of pulmonary thrombi and hence facilitate differential diagnosis of pulmonary embolism from acute myocardial infarction. It was thought that TNK-tPA may be superior in view of its longer biological half-life and less avid uptake by macrophages that would otherwise contribute to high background because of non-clot-selective uptake of the tracer.


METHODS
123I-tyrosylprolylarginyl chloromethyl ketone (123I-YPACK-TNK-tPA) was infused into the systemic circulation of dogs with either pulmonary or right ventricular thrombi induced with thrombogenic tips of modified guide wires. Planar and single-photon emission computed tomography (SPECT) scintigraphic data were obtained, and blood and tissue samples were acquired for analysis of the distribution of the radiotracer over time.


RESULTS
Tracer cleared from blood with an alpha phase half-life of 10 +/- 1 min, paralleling the clearance of unlabeled TNK-tPA. Only minimal release of labeled fragments from liver into blood occurred during the entire time course of the imaging studies. Pulmonary thrombi were visualized with SPECT within 30-120 min in all dogs. Images were superior to those obtained after infusion of labeled wild-type tPA, primarily because of diminished background radioactivity and consequently increased scintigraphic contrast. In one dog which had a right ventricular thrombus, the thrombus was readily detectable in both planar and SPECT images.


CONCLUSIONS
Radiolabeled TNK-tPA in which plasminogen-activating activity has been inhibited biochemically is an excellent 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 disease in patients.
De Bruyn
V H
VH
Cardiovascular Division, Washington University School of Medicine, St Louis, Missouri, USA.
Bergmann
R
R
Keyt
B A
BA
Bennett
W F
WF
Sobel
B E
BE
D000590:Amino Acid Chloromethyl Ketones; D000818:Animals; D004285:Dogs; D006331:Heart Diseases / Q000000981:diagnostic imaging*; D007457:Iodine Radioisotopes; D010960:Plasminogen Activators; D011655:Pulmonary Embolism / Q000000981:diagnostic imaging*; D013927:Thrombosis / Q000000981:diagnostic imaging*; D010959:Tissue Plasminogen Activator; D015899:Tomography, Emission-Computed, Single-Photon
D000590:Amino Acid Chloromethyl Ketones; D007457:Iodine Radioisotopes; C101854:iodotyrosyl-prolyl-arginyl chloromethyl ketone; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator