Technetium-99m labelling of monoclonal antibodies for in vivo radioimmunodiagnostic use

The strong chelating agent diethylenetriaminepentaacetate (DTPA), either as the bicyclic or as the mixed anhydride, is most commonly used to link Tc-99m to proteinaceous compounds. A method for the batch production of DTPA-labelled antibody kits as well as a novel method of DTPA chelation of unpurified ascites fluid is given. Loss of immunoreactivity and in vivo stability occurs with this method. That DTPA conjugation is not the ideal method of labelling, is borne out by the fact that Hnatowich - a pioneer of DTPA-protein chelating - changed to an avidin-biotin labelling system. Modifications of the carbohydrate moiety have also been attempted. High molecular mass polymers with chelate-linkage to the antibodies can bind up to 150 di- or trivalent ions per mole without a loss in antigen-binding activity. Other than DTPA, several chelating agents such as bisthiosemicarbazones, metallothionein and diamide dimercaptide ligands may be used. The simple treatment of a proteinaceous substance with a disulpide-reducing agent, followed by exposure of the reduced protein to a suitable radionuclide, leads to a promising stable radiolabelled product. A Tc-99m-labelled antibody is, subject to FDA approval, scheduled for released by a Kodak-financed company in the near future