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Radioimmunotherapy (RIT) with the alpha-emitter 227Th is currently under evaluation. 227Th is conjugated to the chimeric anti-CD20 monoclonal antibody rituximab, using the chelator p-isothiocyanato-benzyl-DOTA. In this study, the binding of 227Th-DOTA-p-benzyl-rituximab to three different CD-20-positive lymphoma cell lines, Raji, Rael, and Daudi, were evaluated. Equilibrium and kinetic binding experiments were used to determine binding parameters, including the association and dissociation rate constants, the equilibrium dissociation constants, and the total number of antigens for Raji, Rael, and Daudi cells. There were significant differences between the cell lines with respect to both Kdand the total number of antigens. Rael cells had more than three times as many antigens as the other two cell lines, and the functional Kdfound for Rael cells was significantly higher than that found for Raji and Daudi cells. These results were confirmed using flow cytometry. Rituximab was found to be localized in patches on the cell membrane. The findings indicated that 227Th-labeled rituximab has relevant antigen-targeting properties for radioimmunotherapy. [ABSTRACT FROM AUTHOR]

In this study, the feasibility of constructing radioimmunoconjugates by using the novel therapeutic candidate alpha-emitter, 227Th, was evaluated. By use of the bifunctional chelator, p-SCN-benzyl-DOTA, 227Th was conjugated to the two monoclonal antibodies, rituximab and trastuzumab. Their stability in 80 fetal bovine serum at 37°C was measured. The immunoreactive fractions were determined by using CD20- and HER2-positive cells, respectively. The overall labeling yield spanned from 6 to 17. The radioimmunoconjugates demonstrated a relevant stability in serum and showed appropriate antigen-binding abilities. [ABSTRACT FROM AUTHOR]