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.
Department of Radiology, Albany Medical Center, New York 12208, USA.
B R
BR
Line
P B
PB
Weber
R
R
Lukasiewicz
R N
RN
Dansereau
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