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Reduction of Background Activity Through Radiolabeling of Antifibrin Fab' with ^99mTc-Dextran

Departments of Radiology, Pharmacy, and Biochemistry, Albany Medical Center, Albany, New York

Correspondence: For correspondence or reprints contact: Bruce R. Line, MD, Nuclear Medicine, A-72, Albany Medical Center, Albany, NY 12208.

ABSTRACT

Scintigraphic detection of occult disease is limited by background activity in the blood and in the extravascular space that reduces target-specific contrast. To lower nonspecific background activity, we have studied the in vivo biodistribution kinetics of a clot-targeting molecule (MH1 Fab') attached to ^99mTc-dextran. We tested the hypothesis that the complex will have better background clearance than the directly radiolabeled clot-targeting molecule. Methods: Fab' fragments of MH1 Fab' antifibrin antibody were coupled to ^99mTc-sulfhydryl dextran through disulfide exchange, and clot binding bioreactivity was tested in vitro and in vivo in a rabbit jugular vein thrombus model. To assess the background clearance kinetics and extravascular leakage, we studied ^99mTc-dextran, ^99mTc-MH1 Fab', and the ^99mTc-dextran-labeled MH1 Fab' complexes in rats. Results: ^99mTc-radiolabeled dextran derivatives were radiochemically stable and retained clotbinding bioreactivity in vivo. In the rat model, blood and tissue clearance of the ^99mTc-dextran MH1 Fab' constructs was substantially improved relative to directly radiolabeled MH1 Fab'. At 1 h, total and extravascular tracer localizations in lung and muscle were significantly lower for ^99mTc-dextran-radiolabeled MH1 Fab' than for ^99mTc-MH1 Fab' (P < 0.05). Conclusion: The study observations suggest that radiolabeling through a ^99mTc-dextran moiety may improve the detection of pulmonary emboli and other clinically important fixed intravascular targets by lowering nonspecific background activity.

Key Words: image background • dextran • radiopharmaceutical • antifibrin antibody • intravascular targeting