Normal tissue reaction following proton irradiation of the mouse brain

Objective: Radiotherapy leads to inactivation of tumor cells following radiation-induced DNA damage. Compared to conventional photon-based radiotherapy, proton therapy offers the potential of normal tissue sparring due to its favorable depth-dose distribution. However, acute or long-term side effects could still occur due to clinical safety margins and uncertainties about the relative biological effectiveness (RBE). While a variable RBE has been demonstrated in in vitro studies, especially at the end of the proton range, in clinical practice, a constant RBE value of 1.1 is applied. To elucidate the RBE issue based on in vivo experiments, proton irradiation of mouse brains was realized in Dresden.
Methods: Experiments were performed at the experimental beam line [1] of the University Proton Therapy Dresden. For beam characterization and dosimetry, a 2D scintillation detector, ionization chambers and radiochromic films [2] were used. A multi-modality mouse bed suitable for imaging, transportation and irradiation was developed in-house. Like clinical applications, the workflow includes computed tomography scans for treatment planning and X-ray images for refined positioning. By combining these images with proton radiographies [3] of the setup, it was possible to accurately locate the animals relative to the beam. To confirm positioning, DNA damage was visualized by immunofluorescent staining of gH2AX in the irradiated mouse brain.
Results and conclusion: Proton mouse brain irradiation was successfully performed. Distribution of DNA DSB via gH2AX revealed that the proton beam stopped in the beam facing brain hemisphere. The setup enables the comparison to corresponding photon experiments with SAIGRT [4] and clinically relevant long-term experiments, such as measuring cognitive functions and anomalies in imaging, to directly relate potential photon and proton side effects in brain radiotherapy.

[1] Helmbrecht et al. J Instrum 2016
[2] Beyreuther et al. IJPT 2018 (accepted)
[3] Müller et al. Acta Oncologica 2017
[4] Tillner et al. Phys Med Biol 2016