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

• Published in: The Journal of nuclear medicine (1978) Vol. 41; no. 7; pp. 1264 - 1270
• Main Authors: Line, Bruce R, Weber, Peter B, Lukasiewicz, Roberta, Dansereau, Raymond N
• Format: Journal Article
• Language: English
• Published: Reston, VA Soc Nuclear Med 01.07.2000; Society of Nuclear Medicine
• Subjects: Animals; Antibodies, Monoclonal - pharmacokinetics; Biological and medical sciences; Dextrans - chemistry; Dextrans - pharmacokinetics; Fibrin - immunology; Immunoglobulin Fab Fragments; In Vitro Techniques; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Miscellaneous. Technology; Organotechnetium Compounds - chemistry; Organotechnetium Compounds - pharmacokinetics; Rabbits; Radionuclide Imaging; Radionuclide investigations; Radiopharmaceuticals - chemistry; Radiopharmaceuticals - pharmacokinetics; Rats; Rats, Sprague-Dawley; Thrombosis - diagnostic imaging; Tissue Distribution; Radionuclide study; Targeting; Rat; Rodentia; Intravascular space; Binding site; Monoclonal antibody; Scintigraphy; Dextran; Fibrin; In vivo; Vertebrata; Mammalia; Blood substitute; Animal; Distribution; Medical imagery; Kinetics; Diagnosis
• ISSN: 0161-5505; 1535-5667

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 (99m)Tc-dextran. We tested the hypothesis that the complex will have better background clearance than the directly radiolabeled clot-targeting molecule. Fab' fragments of MH1 Fab' antifibrin antibody were coupled to (99m)Tc-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 (99m)Tc-dextran, (99m)Tc-MH1 Fab', and the (99m)Tc-dextran-labeled MH1 Fab' complexes in rats. (99m)Tc-radiolabeled dextran derivatives were radiochemically stable and retained clot-binding bioreactivity in vivo. In the rat model, blood and tissue clearance of the (99m)Tc-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-dextranradiolabeled MH1 Fab' than for (99m)Tc-MH1 Fab' (P < 0.05). The study observations suggest that radiolabeling through a (99m)Tc-dextran moiety may improve the detection of pulmonary emboli and other clinically important fixed intravascular targets by lowering nonspecific background activity.