年間 4 号発行
ISSN 印刷: 0731-8898
ISSN オンライン: 2162-6537
Indexed in
Cellular Internalization and Mechanism of Cytotoxicity of 131I-Rituximab in Raji Cells
要約
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.
-
Kumar Chandan, Vats Kusum, Lohar Sharad P., Korde Aruna, Samuel Grace, Camptothecin Enhances Cell Death Induced by 177Lu-EDTMP in Osteosarcoma Cells, Cancer Biotherapy and Radiopharmaceuticals, 29, 8, 2014. Crossref
-
Kumar Chandan, Shetake Neena, Desai Sejal, Kumar Amit, Samuel Grace, Pandey Badri N., Relevance of radiobiological concepts in radionuclide therapy of cancer, International Journal of Radiation Biology, 92, 4, 2016. Crossref
-
Guleria Mohini, Das Tapas, Kumar Chandan, Amirdhanayagam Jeyachitra, Sarma Haladhar D., Banerjee Sharmila, Preparation of clinical-scale 177 Lu-Rituximab: Optimization of protocols for conjugation, radiolabeling, and freeze-dried kit formulation, Journal of Labelled Compounds and Radiopharmaceuticals, 60, 5, 2017. Crossref
-
Kumar Chandan, Sharma Rohit, Das Tapas, Korde Aruna, Sarma Haladhar, Banerjee Sharmila, Dash Ashutosh, 177Lu-DOTMP induces G2/M cell cycle arrest and apoptosis in MG63 cell line, Journal of Labelled Compounds and Radiopharmaceuticals, 61, 11, 2018. Crossref
-
Kumar Chandan, Sharma Rohit, Vats Kusum, Mallia Madhav B., Das Tapas, Sarma H. D., Dash Ashutosh, Comparison of the efficacy of 177Lu-EDTMP, 177Lu-DOTMP and 188Re-HEDP towards bone osteosarcoma: an in vitro study, Journal of Radioanalytical and Nuclear Chemistry, 319, 1, 2019. Crossref
-
Ma Wenzong, Wang Xudong, Liu Weihao, Ma Huan, Su Yue, Yang Yuanyou, Liu Ning, Wang Yugang, Yang Gen, A Theoretical Model for Predicting and Optimizing In Vitro Screening of Potential Targeted Alpha-Particle Therapy Drugs, Radiation Research, 191, 5, 2019. Crossref
-
Sharma Rohit, Kameswaran Mythili, Dash Ashutosh, ComparativeIn VitroCytotoxicity Studies of177Lu-CHX-A″-DTPA-Trastuzumab and177Lu-CHX-A″-DTPA-F(ab′)2-Trastuzumab in HER2-Positive Cancer Cell Lines, Cancer Biotherapy and Radiopharmaceuticals, 35, 3, 2020. Crossref
-
Kim Eun-Ho, Ko Hae Young, Yu A Ram, Kim Hyeongi, Zaheer Javeria, Kang Hyun Ji, Lim Young-Cheol, Cho Kyung Deuk, Joo Hyun-Yoo, Kang Min Kyoung, Lee Jae Jun, Lee Seung-Sook, Kang Hye Jin, Lim Sang Moo, Kim Jin Su, Inhibition of HIF-1α by Atorvastatin During 131I-RTX Therapy in Burkitt’s Lymphoma Model, Cancers, 12, 5, 2020. Crossref
-
Suman Shishu Kant, Sharma Rohit, Kumar Chandan, Principle and Applications of Immunodiagnostics Using Radioisotope as Tracers, in Immunodiagnostic Technologies from Laboratory to Point-Of-Care Testing, 2021. Crossref
-
Khoo Yoke L, Cheah Swee H, Chong Heilly, Humanization of chimeric anti-CD20 antibody by logical and bioinformatics approach with retention of biological activity, Immunotherapy, 9, 7, 2017. Crossref
-
Kumar Chandan, Sharma Rohit, Repaka KrishnaMohan, Pareri AanchalUdaynath, Dash Ashutosh, Camptothecin enhances 131I-rituximab-induced G1-arrest and apoptosis in Burkitt lymphoma cells, Journal of Cancer Research and Therapeutics, 17, 4, 2021. Crossref
-
Pareri Aanchal Udaynath, Koijam Arunkumar Singh, Kumar Chandan, Breaking the Silence of Tumor Response: Future Prospects of Targeted Radionuclide Therapy, Anti-Cancer Agents in Medicinal Chemistry, 22, 10, 2022. Crossref
-
Samant SaloniArun, Kumar Chandan, Pandey Usha, Fate of 177Lu-CHX-A”-DTPA-Rituximab: In vitro Evaluation in Raji Cell Line, Journal of Radiation and Cancer Research, 2022. Crossref