EVALUATION OF THE VIABILITY OF IN-111-LABELED DTPA COUPLED TO FIBRINOGEN

Abstract

DTPA [diethylenetriamine pentacetic acid] covalently couples to albumin via the cyclic anhydride of DTPA. Using fibrinogen the effect of such coupling on protein viability was studied by both in an in vitro and an in vivo assay. Clotting time remained identical to that of the native protein whether the anhydride-to-protein molar ratio was 1:1 or 5:1. In vivo studies were done in dogs, with human fibrinogen labeled with 125I and 111In. Throughout 130 h, blood clearances for the 2 tracers agreed whether with 1:1 or 5:1 coupling. In a dog model with a thrombogenic catheter, the clot/blood ratios for the 2 radiotracers agreed within experimental error. Finally, 1:1-coupled canine fibrinogen, labeled with 111In, was administered to dogs with a catheter in a jugular vein, and scintigrams at 24 h clearly showed clotting along the length of the catheter. Evidently, fibrinogen coupled to DTPA retains its viability, behaving like radioiodinated fibrinogen in vivo, and 111In-labeled fibrinogen looks promising as a clinical diagnostic agent.