Abstract
The rare abscopal effect in radiotherapy is thought to result from immune-activating damage-associated molecular patterns, such as high mobility group box-1 protein (HMGB1), released from cancer cells. While external irradiation of cancer cells increases HMGB1 release, it remains unclear whether internal radiotherapy with 131I-meta-iodobenzylguanidine (131I-MIBG) induces similar effects. This study aimed to determine if HMGB1 is released from human-derived cancer and normal cells after 131I-MIBG administration. The number of cells, extracellular lactate dehydrogenase (LDH) and HMGB1 were measured in H441 and human keratinocyte cell line (HaCaT) at 1 day after 2- and 10-Gy X-ray irradiation. Accumulations of 131I-MIBG in SH-SY5Y and HaCaT were measured at 60 min after 131I-MIBG (0.37, 1.85 and 3.7 MBq/well) administration. The number of cells, extracellular LDH and HMGB1 were measured at 1 day after 131I-MIBG treatment. Results: The total number of cells decreased in both H441 and HaCaT at 1 day after 10-Gy X-ray irradiation. Extracellular LDH and HMGB1 from H441 after 10-Gy X-ray irradiation were significantly increased, while no increase was observed in HaCaT after 2- and 10-Gy X-ray irradiation. After 1.85 MBq (~4-Gy by converting of PHITS simulation) and 3.7 MBq 131I-MIBG (8-Gy) administrations, the total number of cells decreased in both SH-SY5Y and HaCaT at 1 day after 131I-MIBG administration. Extracellular LDH and HMGB1 were both significantly increased in SH-SY5Y, but only extracellular LDH was significantly increased in HaCaT. HMGB1 was released from neuroblastoma cells but not from normal cells after 131I-MIBG administration. A combination of 131I-MIBG and immunotherapy may be feasible.