Reduction of background activity through radiolabeling of antifibrin Fab' with Tc-99m-dextran

Scintigraphic detection of occult disease is limited by background activity in the blood and in the extravascular space that reduces target-specific c ontrast. To lower nonspecific background activity, we have studied the in v ivo biodistribution kinetics of a clot-targeting molecule (MH1 Fab') attach ed to Tc-99m-dextran. We tested the hypothesis that the complex will have b etter background clearance than the directly radiolabeled clot-targeting mo lecule. Methods: Fab' fragments of Mi-ii Fab' antifibrin antibody were coup led to Tc-99m-sulfhydryl dextran through disulfide exchange, and clot bindi ng bioreactivity was tested in vitro and in vivo in a rabbit jugular vein t hrombus model. To assess the background clearance kinetics and extravascula r leakage, we studied Tc-99m-dextran, (TC)-T-99m-MH1 Fab', and the (99m)wc- dextran-labeled MH1 Fab' complexes in rats. Results: Tc-99m-radiolabeled de xtran derivatives were radiochemically stable and retained clot-binding bio reactivity in vivo. In the rat model, blood and tissue clearance of the Tc- 99m-dextran MH1 Fab' constructs was substantially improved relative to dire ctly radiolabeled MH1 Fab'. At 1 h, total and extravascular tracer localiza tions in lung and muscle were significantly lower for Tc-99m-dextran-radiol abeled MH1 Fab' than for Tc-99m-MH1 Fab' (P < 0.05). Conclusion: The study observations suggest that radiolabeling through a Tc-99m-dextran moiety may improve the detection of pulmonary emboli and other clinically important f ixed intravascular targets by lowering nonspecific background activity.