Evaluation of the Binding of Radiolabeled Rituximab to CD20-Positive Lymphoma Cells: AnIn VitroFeasibility Study Concerning Low-Dose-Rate Radioimmunotherapy with theα-Emitter227Th
- 1 August 2007
- journal article
- research article
- Published by Mary Ann Liebert Inc in Cancer Biotherapy & Radiopharmaceuticals
- Vol. 22 (4), 469-479
- https://doi.org/10.1089/cbr.2007.371
Abstract
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.Keywords
This publication has 16 references indexed in Scilit:
- High-Linear Energy Transfer Irradiation Targeted to Skeletal Metastases by the α-Emitter 223Ra: Adjuvant or Alternative to Conventional Modalities?Clinical Cancer Research, 2006
- The average number of alpha-particle hits to the cell nucleus required to eradicate a tumour cell populationPhysics in Medicine & Biology, 2006
- Initial evaluation of 227Th-p-benzyl-DOTA-rituximab for low-dose rate α-particle radioimmunotherapyNuclear Medicine and Biology, 2006
- First Clinical Experience with α-Emitting Radium-223 in the Treatment of Skeletal MetastasesClinical Cancer Research, 2005
- Treatment of Neuroblastoma Meningeal Carcinomatosis with Intrathecal Application of α-Emitting Atomic Nanogenerators Targeting Disialo-Ganglioside GD2Clinical Cancer Research, 2004
- Cyclooxygenase-2 inhibitors in colorectal cancerSeminars in Oncology, 2003
- Radiation doses to non-Hodgkin's lymphoma cells and normal bone marrow exposed in vitro. Comparison of an α-emitting radioimmunoconjugate and external γ-irradiationInternational Journal of Radiation Biology, 2002
- Tumor Therapy with Targeted Atomic NanogeneratorsScience, 2001
- [65] Determination of the true immunoreactive fraction of monoclonal antibodies after radiolabelingMethods in enzymology, 1986
- A graphic method for the determination and presentation of binding parameters in a complex systemAnalytical Biochemistry, 1967