THIOLATIONS, TC-99M LABELINGS, AND ANIMAL IN-VIVO BIODISTRIBUTIONS OFDIVALENT MONOCLONAL-ANTIBODY FRAGMENTS

A number of divalent monoclonal antibody fragments have been derivatiz ed with a bifunctional reagent containing a latent thiol group, and th e conjugates were thiol-deprotected by exposure to aqueous hydroxylami ne. This two-step procedure enabled convenient Tc-99m labeling of thio lated MAb divalent fragments, using either preformed Tc-99m-glucohepto nate or [Tc-99m]pertechnetate and single-vial lyophilized formulations of the conjugate and tin. Nonspecific incorporation of radiolabel was negligible, if any, when using nonthiolated antibodies. In animal bio distributions, in nude mice bearing LS174T human colon carcinoma xenog rafts, the Tc-99m-labeled MAb divalent fragments studied were found to result in a 3-fold reduction in the kidney uptake of radioactivity at 24 h, compared to a Tc-99m-Fab, and also to lead to improvements in o ther tumor:nontumor ratios.