Abstract: Methods for preparing metabolically stable, covalently crosslinked F(ab').sub.2 fragments of antibody molecules for use in labeled form as in vivo diagnostic and therapeutic agents, the stabilized F(ab').sub.2 fragments so produced in free form or conjugated to a chemical moiety, kits containing such fragments, and methods of using these fragments for diagnosis or therapy, are disclosed. In the method, crosslinking is carried out after reduction of inter-heavy chain disulfide bonds, but before cleavage of the crosslinked antibody to produce the F(ab').sub.2 molecules.

Abstract: Metal radionuclide labeled proteinaceous substances which contain, in their native states, disulfide (cysteine) linkages, which find use in diagnosis and treatment of a variety of pathologic conditions. The radionuclide labeled proteinaceous substances of the present invention are formed by the treatment of the proteinaceous substance of interest with a disulfide reducing agent, followed by reaction of the reduced proteinaceous substance ("H-treated product") with a suitable radionuclide species containing, for example, .sup.99m Tc, .sup.186 Re and .sup.188 Re, or .sup.67 Cu. It has been found that the H-treated products, e.g., antibodies, react specifically with radionuclide species to form stable radionuclide labeled antibodies or other radiolabeled products. The H-treated products may be stabilized or modified in a variety of ways prior to and subsequent to complexation with the metal radionuclide.