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Simulation of water radiolysis and the subsequent chemistry provides important information on the effect of ionizing radiation on biological material. The Geant4 Monte Carlo toolkit has added chemical processes via the Geant4-DNA project. The TOPAS tool simplifies the modeling of complex radiotherapy applications with Geant4 without requiring advanced computational skills, extending the pool of users. Thus, a new extension to TOPAS, TOPAS-nBio, is under development to facilitate the configuration of track-structure simulations as well as water radiolysis simulations with Geant4-DNA for radiobiological studies. In this work, radiolysis simulations were implemented in TOPAS-nBio. Users may now easily add chemical species and their reactions, and set parameters including branching ratios, dissociation schemes, diffusion coefficients, and reaction rates. In addition, parameters for the chemical stage were re-evaluated and updated from those used by default in Geant4-DNA to improve the accuracy of chemical yields. Simulation results of time-dependent and LET-dependent primary yields Gx (chemical species per 100 eV deposited) produced at neutral pH and 25 °C by short track-segments of charged particles were compared to published measurements. The LET range was 0.05–230 keV µm−1. The calculated Gx values for electrons satisfied the material balance equation within 0.3%, similar for protons albeit with long calculation time. A smaller geometry was used to speed up proton and alpha simulations, with an acceptable difference in the balance equation of 1.3%. Available experimental data of time-dependent G-values for agreed with simulated results within 7%  ±  8% over the entire time range; for over the full time range within 3%  ±  4%; for H2O2 from 49%  ±  7% at earliest stages and 3%  ±  12% at saturation. For the LET-dependent Gx, the mean ratios to the experimental data were 1.11  ±  0.98, 1.21  ±  1.11, 1.05  ±  0.52, 1.23  ±  0.59 and 1.49  ±  0.63 (1 standard deviation) for , , H2, H2O2 and , respectively. In conclusion, radiolysis and subsequent chemistry with Geant4-DNA has been successfully incorporated in TOPAS-nBio. Results are in reasonable agreement with published measured and simulated data. [ABSTRACT FROM AUTHOR]

Whilst Monte Carlo (MC) simulations of proton energy deposition have been well-validated at the macroscopic level, their microscopic validation remains lacking. Equally, no gold-standard yet exists for experimental metrology of individual proton tracks. In this work we compare the distributions of stochastic proton interactions simulated using the TOPAS-nBio MC platform against confocal microscope data for Al2O3:C,Mg fluorescent nuclear track detectors (FNTDs). We irradiated mm3 FNTD chips inside a water phantom, positioned at seven positions along a pristine proton Bragg peak with a range in water of 12 cm. MC simulations were implemented in two stages: (1) using TOPAS to model the beam properties within a water phantom and (2) using TOPAS-nBio with Geant4-DNA physics to score particle interactions through a water surrogate of Al2O3:C,Mg. The measured median track integrated brightness (IB) was observed to be strongly correlated to both (i) voxelized track-averaged linear energy transfer (LET) and (ii) frequency mean microdosimetric lineal energy, , both simulated in pure water. Histograms of FNTD track IB were compared against TOPAS-nBio histograms of the number of terminal electrons per proton, scored in water with mass-density scaled to mimic Al2O3:C,Mg. Trends between exposure depths observed in TOPAS-nBio simulations were experimentally replicated in the study of FNTD track IB. Our results represent an important first step towards the experimental validation of MC simulations on the sub-cellular scale and suggest that FNTDs can enable experimental study of the microdosimetric properties of individual proton tracks. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (GNPs) have shown potential as dose enhancers for radiation therapy. Since damage to the genome affects the viability of a cell, it is generally assumed that GNPs have to localise within the cell nucleus. In practice, however, GNPs tend to localise in the cytoplasm yet still appear to have a dose enhancing effect on the cell. Whether this effect can be attributed to stress-induced biological mechanisms or to physical damage to extra-nuclear cellular targets is still unclear. There is however growing evidence to suggest that the cellular response to radiation can also be influenced by indirect processes induced when the nucleus is not directly targeted by radiation. The mitochondrion in particular may be an effective extra-nuclear radiation target given its many important functional roles in the cell. To more accurately predict the physical effect of radiation within different cell organelles, we measured the full chemical composition of a whole human lymphocytic JURKAT cell as well as two separate organelles; the cell nucleus and the mitochondrion. The experimental measurements found that all three biological materials had similar ionisation energies  ∼70 eV, substantially lower than that of liquid water  ∼78 eV. Monte Carlo simulations for 10–50 keV incident photons showed higher energy deposition and ionisation numbers in the cell and organelle materials compared to liquid water. Adding a 1% mass fraction of gold to each material increased the energy deposition by a factor of  ∼1.8 when averaged over all incident photon energies. Simulations of a realistic compartmentalised cell show that the presence of gold in the cytosol increases the energy deposition in the mitochondrial volume more than within the nuclear volume. We find this is due to sub-micron delocalisation of energy by photoelectrons, making the mitochondria a potentially viable indirect radiation target for GNPs that localise to the cytosol. [ABSTRACT FROM AUTHOR]