Evaluation of the Binding of Radiolabeled Rituximab to CD20-Positive Lymphoma Cells: An In Vitro Feasibility Study Concerning Low-Dose-Rate Radioimmunotherapy with the alpha -Emitter super(227)Th
Radioimmunotherapy (RIT) with the alpha-emitter super(227)Th is currently under evaluation. super(227)Th is conjugated to the chimeric anti-CD20 monoclonal antibody rituximab, using the chelator p-isothiocyanato-benzyl-DOTA. In this study, the binding of super(227)Th-DOTA-p-benzyl-rituximab to three...
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Published in | Cancer biotherapy & radiopharmaceuticals Vol. 22; no. 4; pp. 469 - 479 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
01.08.2007
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Online Access | Get full text |
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Abstract | Radioimmunotherapy (RIT) with the alpha-emitter super(227)Th is currently under evaluation. super(227)Th is conjugated to the chimeric anti-CD20 monoclonal antibody rituximab, using the chelator p-isothiocyanato-benzyl-DOTA. In this study, the binding of super(227)Th-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 K sub(d) 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 K sub(d) 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 super(227)Th-labeled rituximab has relevant antigen-targeting properties for radioimmunotherapy. |
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AbstractList | Radioimmunotherapy (RIT) with the alpha-emitter super(227)Th is currently under evaluation. super(227)Th is conjugated to the chimeric anti-CD20 monoclonal antibody rituximab, using the chelator p-isothiocyanato-benzyl-DOTA. In this study, the binding of super(227)Th-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 K sub(d) 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 K sub(d) 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 super(227)Th-labeled rituximab has relevant antigen-targeting properties for radioimmunotherapy. |
Author | Kaalhus, O Selbo, P K Dahle, J Larsen, R H Melhus, K B Stokke, T |
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Title | Evaluation of the Binding of Radiolabeled Rituximab to CD20-Positive Lymphoma Cells: An In Vitro Feasibility Study Concerning Low-Dose-Rate Radioimmunotherapy with the alpha -Emitter super(227)Th |
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