%0 Journal Article %A Kumar, Chandan %A Pandey, Badri Narain %A Samuel, Grace %A Venkatesh, Meera %D 2013 %I Begell House %K 131I-rituximab, rituximab, lymphoma, toxicity, apoptosis, cellular internalization %N 2 %P 91-99 %R 10.1615/JEnvironPatholToxicolOncol.2013006843 %T Cellular Internalization and Mechanism of Cytotoxicity of 131I-Rituximab in Raji Cells %U https://www.dl.begellhouse.com/journals/0ff459a57a4c08d0,58992bb411ae4476,793bd1b1075747a9.html %V 32 %X Rituximab labeled with radioiodine (131I-rituximab) has a large potential to be employed for targeted therapy of non-Hodgkin's lymphoma. Studies of parameters such as cellular internalization, stability of 131I-rituximab bound to CD20 receptor of tumor cells, and the mechanism underlying cytotoxicity induced by 131I-rituximab will be useful for better clinical application. In this article we describe the efficacy of 131I-rituximab in CD20-expressing Raji cells. Rituximab labeled with 131I was purified on a PD-10 column and characterized using high-performance liquid chromatography and paper electrophoresis. Raji cells treated with 131I-rituximab (1.85 MBq for 2 hours) were washed then incubated. The culture medium collected from treated cells showed increased radioactivity over a longer period (>6 hours), probably due to the deiodination/degradation of 131I-rituximab. The tumor cells treated with 131I-rituximab showed time-dependent internalization of radioactivity, and at 12 hours the radioactivity was almost equally distributed in the membrane and cytoplasm. At 24 hours ~70% of the radioactivity was internalized. Cellular toxicity after 131I-rituximab treatment showed a time-dependent increase in toxicity as estimated by lactate dehydrogenase. Tumor cells treated with 131I-rituximab showed significantly higher toxicity and apoptosis compared with the those treated with the same concentration of unlabeled rituximab. The increased apoptotic death in cells treated with 131I-rituximab was associated with cleavage of poly ADP ribose polymerase and upregulation of p53 protein. This study provides a deeper understanding about the cellular internalization/stability of 131I-rituximab bound to the CD20 receptor and its efficacy in killing Raji cells. %8 2013-09-19