In Vitro Evaluation of Radioprotective and Radiosensitizing Effects of Rituximab

作者: N. S. Kapadia , J. M. Engles , R. L. Wahl

DOI: 10.2967/JNUMED.107.043752

关键词: Flow cytometryLymphomaImmunologyIonizing radiationCD20Cancer researchCell cycleRituximabMonoclonal antibodyChemistryRadioimmunotherapy

摘要: UNLABELLED Clinical radioimmunotherapies with anti-CD20 monoclonal antibodies involve administering a predose of unlabeled to favorably alter the biodistribution profile subsequently administered radiolabeled and mediate antitumor effects. Prior in vitro data suggested that radiosensitize lymphoma cells as well. We assessed antiproliferative possible radiosensitizing capabilities an antibody, rituximab. METHODS Luciferase-transfected (via lentivirus vector) CD20+ human Raji log-phase growth were incubated or without rituximab (20 microg/mL) for either 1 24 h before external-beam radiation exposure. Cell counts measured luciferase assay at 24-h intervals. Subsets these also analyzed cell cycle status by flow cytometry. RESULTS Rituximab pretreatment irradiation found significantly inhibit tumor compared alone (by factor 0.40 Gy [P < 0.01]). One hour modestly radiosensitized dose 1.03 results nonirradiated cells). At higher doses (2 12 Gy), paradoxically radioprotected factors 0.25 (P 0.01) 0.54 0.05), respectively. predosing was be 4 2.84 0.01]) but radioprotective 1, 8, 0.10 0.01], 2.50 2.07 0.05], respectively). These correlated retardation 6 d after administration, determined CONCLUSION demonstrated direct effect absence radiation. lower levels exposure, cells. radiation, protected against ionizing possibly through effects on cycle. radiobiologic should carefully considered design radioimmunotherapeutic trials.

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