Indium-111 labeled tissue plasminogen activator

Although radiolabeled fibrinogen has been used successfully for detection of thromboemboli by imaging, plasminogen activators offer the advantage of clot detection after active fibrin deposition has ceased. The authors have labeled recombinant tissue plasminogen activator (rTPA) with indium-111 (In) and studied its properties in vivo. Using the cyclic anhydride and standard methodology, an average of about 1 DTPA group per molecule was attached and the protein was labeled with In to a specific activity of 2-3 mCi/mg. Size exclusion HPLC showed each preparation to be of high radiochemical purity and that the In was bound only to the DTPA groups. In vivo clot localization was investigated using a canine clot model in which thrombogenic catheters are placed in a femoral artery and/or in the jugular vein prior to the administration of labeled rTPA. After administration of 0.5-1.0 mg of In-rTPA, blood and serum activity levels were found to decrease with a half time of 8 +- 1 min. in good agreement with the literature value of 7 min. for unlabeled rTPA. Clot:blood and clot:serum ratios were found to increase rapidly, in one study reaching 6.3 after 31 min. Because of the short residence time of rTPA in blood, activity in cardiac and pulmonary blood pools decreased rapidly such that clots were visualized within minutes of injection. The authors conclude that rTPA may be labeled with In without destroying the molecule's ability to localize in clot and that, with this agent, useful images of forming clot may be obtained within one hour of administration. This protein may therefore be ideal for imaging pulmonary and cardiac thromboemboli by gamma scintigraphy