Preprint Article Version 1 This version is not peer-reviewed

Release of HMGB1 from Human-Derived Cancer and Normal Cells by Internal Targeted Radiotherapy with 131Iodine-Labeled m-Iodobenzylguanidine

Version 1 : Received: 29 October 2024 / Approved: 29 October 2024 / Online: 30 October 2024 (02:18:35 CET)

How to cite: Sato, K.; Handa, R.; Yao, J.; Hirayama, Y.; Hamada, Y.; Yamagata, J.; Watanabe, T.; Mizutani, A.; Kobayashi, M.; Nishii, R.; Kawai, K. Release of HMGB1 from Human-Derived Cancer and Normal Cells by Internal Targeted Radiotherapy with 131Iodine-Labeled m-Iodobenzylguanidine. Preprints 2024, 2024102345. https://doi.org/10.20944/preprints202410.2345.v1 Sato, K.; Handa, R.; Yao, J.; Hirayama, Y.; Hamada, Y.; Yamagata, J.; Watanabe, T.; Mizutani, A.; Kobayashi, M.; Nishii, R.; Kawai, K. Release of HMGB1 from Human-Derived Cancer and Normal Cells by Internal Targeted Radiotherapy with 131Iodine-Labeled m-Iodobenzylguanidine. Preprints 2024, 2024102345. https://doi.org/10.20944/preprints202410.2345.v1

Abstract

The rare abscopal effect during radiotherapy is thought to be caused by the release of immune-stimulated damage-associated molecular patterns, such as high mobility group box-1 protein (HMGB1), from cancer cells. Although external irradiation of cancer cells increases HMGB1 release, it is not clear if HMGB1 is released from cells after administering 131I-labeled m-iodobenzylguanidine (131I-MIBG) as an internal targeted radiotherapeutic agent. This study aimed to determine if HMGB1 is released from human-derived cancer and normal cells after administering 131I-MIBG. Methods: Extracellular lactate dehydrogenase (LDH) and HMGB1 released from H441 (human-derived lung adenocarcinoma cell line) and HaCaT (human keratinocyte cell line) 1 day after 2- and 10-Gy X-ray irradiation were measured. Accumulations of 131I-MIBG in SH-SY5Y (human-derived neuroblastoma cell line) and HaCaT were measured 60 min after administering 131I-MIBG (0.37, 1.85, 3.7 MBq/well). Extracellular LDH and HMGB1 released from SH-SY5Y and HaCaT 1 day after administering 131I-MIBG were also measured. Results: The extracellular LDH and HMGB1 released from H441 after 10-Gy X-ray irradiation were significantly increased. However, the extracellular LDH and HMGB1 released from HaCaT after 2-Gy and 10-Gy X-ray irradiation were not increased. After administering 1.85 MBq and 3.7 MBq 131I-MIBG, the extracellular LDH and HMGB1 released from SH-SY5Y were both significantly increased, but only the extracellular LDH released from HaCaT was significantly increased. Conclusions: HMGB1 was released from neuroblastomas but not from normal cells after 131I-MIBG administration, suggesting that a combination of 131I-MIBG and immunotherapy may be feasible.

Keywords

damage-associated molecular patterns; high mobility group box-1 protein; X-ray; 131I-labeled m-iodobenzylguanidine; lactate dehydrogenase; immunotherapy

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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