Reduction of background activity through radiolabeling of antifibrin Fab' with 99mTc-dextran.
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.


METHODS
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.


RESULTS
(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).


CONCLUSIONS
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.
Line
B R
BR
Department of Radiology, Albany Medical Center, New York 12208, USA.
Weber
P B
PB
Lukasiewicz
R
R
Dansereau
R N
RN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics; D005337:Fibrin / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments; D066298:In Vitro Techniques; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000000981:diagnostic imaging; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D003911:Dextrans; D007140:Immunoglobulin Fab Fragments; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C034146:technetium Tc 99m dextran; D005337:Fibrin