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Pharmacokinetics of Radioiodinated Streptokinase

University of California School of Medicine, Davis, California

Correspondence: For reprints contact: Gerald L. DeNardo, Div. of Nuclear Medicine, University of California School of Medicine, Davis, Calif. 95616.

ABSTRACT

The pharmacokinetics of radioiodinated streptokinase have been investigated in mice and dogs in order to explore further its potential usefulness as a radiopharmaceutical to detect thrombi and neoplasms. The purified streptokinase used in these studies showed no alteration in its physical or enzymatic properties following radioiodination.

In the mouse, radioiodinated streptokinase accumulated rapidly in the liver and at 4 hr, large amounts of free iodine were detected in the plasma. The plasma clearance curve in dogs was biexponential showing that 70% of the protein-bound radioactivity was cleared with a half-life of 15–25 min while the remaining 30% was cleared with a half-life of 60–80 min. Seventy percent of the plasma radioactivity appeared as free iodine after 4 hr. No change in clearance was obtained by preloading animals with unlabeled streptokinase.

Based primarily on the rapid plasma clearance, deiodination, and possible limitations of effectiveness of preloading with unlabeled streptokinase, the results of these studies are in accord with the conclusion that radioiodinated streptokinase may have restricted usefulness as a radiopharmaceutical for detecting thrombi and neoplasms. The full extent of its potential usefulness, however, awaits the provision of further in vivo and in vitro studies directed at testing a covalently modified enzyme that retains streptokinase activity but whose immunologic properties have been altered so that the enzyme is not as rapidly cleared from the plasma.