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(Circulation. 1995;92:1320-1325.)
© 1995 American Heart Association, Inc.

Articles

Visualization of Thrombi in Pulmonary Arteries With Radiolabeled, Enzymatically Inactivated Tissue-Type Plasminogen Activator

Presented in part at the 67th Scientific Sessions of the American Heart Association, Dallas, Tex, November 14-17, 1994, and published in abstract form in Circulation. 1994;90(pt 2):I-369.

Van H. De Bruyn, MD; Steven R. Bergmann, MD, PhD; Bruce A. Keyt, PhD; Burton E. Sobel, MD

From the Cardiovascular Division, Washington University School of Medicine, St Louis, Mo (V.H.DeB., S.R.B.); Cardiovascular Research, Genentech, Inc, South San Francisco, Calif (B.A.K.); and the Department of Medicine, the University of Vermont, Burlington (B.E.S.).

Correspondence to Van H. De Bruyn, MD, Cardiovascular Division, Box 8086, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110.

Background Despite the high frequency of pulmonary thromboembolism and its significant morbidity and mortality, diagnosis remains suboptimal. We have been developing a method for prompt detection with the use of radiolabeled, inactivated tissue-type plasminogen activator (TPA) and performed the present study to determine whether its use permits rapid scintigraphic visualization of pulmonary thrombi in vivo.

Methods and Results The thrombolytic, but not fibrin-binding, property of TPA was inactivated with a tripeptide chloromethyl ketone (YPACK) that had already been iodinated with ¹²³I to radiolabel the TPA. Pulmonary arterial thrombosis was induced in nine dogs with the use of guide wires modified to provide thrombogenic tips. ¹²³I-YPACK-TPA (1.1 to 7.8 mCi, 0.5 to 7.8 mg) was infused for 5 minutes into either the systemic or the pulmonary circulation. Clearance of radioactivity from the blood was rapid and indistinguishable from that of unlabeled, thrombolytically active TPA, with only 6.7±1.0% (mean±SEM) of peak radioactivity remaining after 60 minutes and minimal release of labeled fragments from the liver during this interval. Thrombi were visualized with single photon emission computed tomography and/or planar imaging 40 to 120 minutes after infusion of tracer in all seven animals given at least 3.7 mCi of ¹²³I-YPACK-TPA. Ratios of radioactivity in thrombus (wet mass, 610±64 mg) to blood were high (14±3:1).

Conclusions The use of radiolabeled TPA in which thrombolytic activity is inactivated permits prompt scintigraphic detection of thrombi in pulmonary arteries in vivo.

Key Words: plasminogen activators • embolism • thrombosis • lung

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