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Evaluation of the Binding of Radiolabeled Rituximab to CD20-Positive Lymphoma Cells: An In Vitro Feasibility Study Concerning Low-Dose-Rate Radioimmunotherapy with the α -Emitter 227 Th

2007; Mary Ann Liebert, Inc.; Volume: 22; Issue: 4 Linguagem: Inglês

10.1089/cbr.2007.371

1557-8852

Katrine B. Melhus, Roy H. Larsen, Trond Stokke, Olav Kaalhus, Pål Kristian Selbo, Jostein Dahle,

Synthesis and Biological Evaluation

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 Kd and the total number of antigens. Rael cells had more than three times as many antigens as the other two cell lines, and the functional Kd found 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.