Dose- and time-dependent relative biological effect of proton in different intracerebral cells

To further explore relative biological effectiveness (RBE) variability, the RBE of different intracerebral cells at various irradiation (IR) dosages and time were determined in this study. A total of 120 rabbits were randomly divided into proton groups (0, 10, 20, 30, 40 Gy, RBE) (n = 3) and photon groups (0, 10, 20, 30, 40 Gy) (n = 3). The rabbits were sacrificed at 2, 4, 6, 8 weeks after brain IR. Neuronal survival, identified via Hematoxylin and Eosin (H&E) staining, and immunohistochemical detection of neurofilament (NF), Olig2, and CD68 in the hippocampus and thalamus, were analyzed. Dose- and time-dependent RBE curves were fitted using the LQ model. Proton IR showed higher neuronal survival at 4-, 6-, and 8-weeks post 10 Gy, 20 Gy, 30 Gy IR (p < 0.05) compared to photon IR. Oligodendrocyte populations in photon group at 4-, 6-, and 8-weeks post 10 Gy IR and 6-, 8-weeks post 20 Gy were consistently higher than proton subgroups (p < 0.05). While proton IR showed higher microglial activation which was observed only at 4-weeks post 30y IR. Proton RBE for neurons and oligodendrocytes remained below 1.1 but exceeded 1.1 for microglial activation. These findings demonstrate the dose- and time- dependent nature of proton RBE and suggest brain tissue tolerates higher proton IR doses compared to photon IR, which fully confirmed the biological advantages of proton IR. These will help clinicians more precisely set the organ limit at risk and tailor radiotherapy plans.