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Carbon ion radiotherapy is an emerging cancer treatment modality that has a greater therapeutic window than conventional photon radiotherapy. To maximize the efficacy of this extremely scarce medical resource, it is important to identify predictive biomarkers of higher carbon ion relative biological effectiveness (RBE) over photons. Here we show that the carbon ion RBE in human cancer cells correlates with the cellular uptake of ⁶⁴Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (⁶⁴Cu-ATSM), a potential radioligand that reflects an over-reduced intracellular environment. High RBE/⁶⁴Cu-ATSM cells show greater steady-state levels of antioxidant proteins and increased capacity to scavenge reactive oxygen species in response to X-rays than low RBE/⁶⁴Cu-ATSM counterparts. These data suggest that the cellular antioxidant activity is a possible determinant of carbon ion RBE predictable by ⁶⁴Cu-ATSM uptake.

Carbon ion radiotherapy is an emerging cancer treatment modality that has a greater therapeutic window than conventional photon radiotherapy. To maximize the efficacy of this extremely scarce medical resource, it is important to identify predictive biomarkers of higher carbon ion relative biological effectiveness (RBE) over photons. We addressed this issue by focusing on cellular antioxidant capacity and investigated ⁶⁴Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (⁶⁴Cu-ATSM), a potential radioligand that reflects an over-reduced intracellular environment. We found that the carbon ion RBE correlated with ⁶⁴Cu-ATSM uptake both in vitro and in vivo. High RBE/⁶⁴Cu-ATSM …