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The spatial distribution of energy deposition events is an essential aspect in the determination of the radiobiological effects of ionizing radiation at the cellular level. Microdosimetry provides a theoretical framework for the description of these events, and has been used in several studies to address problems such as the characterization of Linear Energy Transfer (LET) and Relative Biological Effectiveness (RBE) of ion beams for proton therapy applications. Microdosimetry quantities and their distributions can be obtained by means of Monte Carlo simulations. In this work, we present a track structure Monte Carlo (MC) application, based on Geant4-DNA, for the computation of microdosimetric distributions of protons in liquid water. This application provides two sampling methods uniform and weighted, for the scoring of the quantities of interest in spherical sites, with diameters ranging from 1 to 10 μm. As an element of novelty, the work shows the approach followed to calculate, without resorting to dedicated simulations, the distribution of energy imparted to the site per electronic collision of the proton, which can be used to obtain the macroscopic dose-averaged LET as proposed by Kellerer. Furthermore, in this work the concept of effective mean chord length is proposed to take into account δ-ray influx and escape in the calculation of macroscopic dose-averaged LET for proton track segments and retrieve the agreement predicted by Kellerer’s formula. Finally, the results obtained demonstrate that our MC application is reliable and computational-efficient to perform calculations of microdosimetric distributions and dose-averaged LET of proton track segments in liquid water.

A feasibility study of an experimental setup for the irradiation of biological samples at the cyclotron facility installed at the National Centre of Accelerators (Seville, Spain) is presented. This cyclotron, which counts on an external beam line for interdisciplinary research purposes, produces an 18 MeV proton beam, which is suitable for the irradiation of mono-layer cultures for the measurement of proton cell damages and Relative Biological Effectiveness (RBE) at energies below the beam nominal value. Measurements of this kind are of interest for proton therapy, since the variation of proton RBE at the distal edge of the Bragg curve may have implications in clinical proton therapy treatments. In the following, the characteristics of the beam line and the solutions implemented for the irradiation of biological samples are described. When dealing with the irradiation of cell cultures, low beam intensities and broad homogeneous irradiation fields are required, in order to assure that all the cells receive the same dose with a suitable dose rate. At the cyclotron, these constraints have been achieved by completely defocusing the beam, intercepting the beam path with tungsten scattering foils and varying the exit-window-to-sample distance. The properties of the proton beam thus obtained have been analysed and compared with Monte Carlo simulations. The results of this comparison, as well as the experimental measurement of the lateral dose profiles expected at the position of samples are presented. Meaningful dose rates of about 2⁻3 Gy/min have been obtained. Homogeneous lateral dose profiles, with maximum deviations of 5%, have been measured at a distance of approximately 50 cm in air from the exit window, placing a tungsten scattering foil of 200 μm in the beam path.