Relative biological effectiveness of pulsed and continuous 20 MeV protons for micronucleus induction in 3D human reconstructed skin tissue

Background and purposeLaser accelerated radiotherapy is a prospect for cancer treatment with proton and/or carbon ion beams that is currently under fast development. In principal, ultra fast, high-energy laser pulses will lead to a “pulsed” delivery of the induced ion beam with pulse durations of 1 ns and below, whereas conventional proton beams deriving from a cyclotron or synchrotron apply the dose within 100 ms (“continuous”).Materials and methodsA simulation of both irradiation modes could be established at the Munich tandem accelerator with a 20 MeV proton beam, and a wide-field fast scanning system was implemented that allowed for application of up to 5 Gy per tissue voxel in a single pulse. The relative biological effectiveness (RBE) of pulsed and continuous modes of irradiation with 20 MeV protons relative to the reference radiation 70 kV X-rays was examined in a human tissue model (3D human reconstructed skin, EpiDermFT™) which preserves the three-dimensional geometric arrangement and communication of cells present in tissues in vivo. Using the induction of micronuclei (MN) in keratinocytes as the biological endpoint, the RBE was calculated as the ratio between the dose of 70 kV X-rays and 3 Gy of 20 MeV protons (pulsed or continuous) which produced equal response.ResultsFor pulsed and continuous 20 MV proton exposures of the human skin model, RBE values of 1.08 ± 0.20 and 1.22 ± 0.15 versus 70 kV X-rays were obtained in a first experiment and 1.00 ± 0.14 and 1.13 ± 0.14 in a second experiment during distinct beam access times, respectively. The ∼10% difference in RBE between the respective irradiation modes in both experiments was associated with large uncertainties which were not statistically significant (p ≈ 0.5).ConclusionThese findings represent an important step on the way towards application of laser-accelerated protons for clinical radiotherapy. Further clinically relevant endpoints in normal and tumor tissue have to be evaluated.