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Monte Carlo multi-track chemistry simulations were carried out to study the effects of high dose rates on the transient yields of hydronium ions (H₃O⁺) formed during low linear energy transfer (LET) radiolysis of both pure, deaerated and aerated liquid water at 25 °C, in the interval ~1 ps–10 μs. Our simulation model consisted of randomly irradiating water with <i>N</i> interactive tracks of 300-MeV incident protons (LET ~ 0.3 keV/μm), which simultaneously impact perpendicularly on the water within a circular surface. The effect of the dose rate was studied by varying <i>N</i>. Our calculations showed that the radiolytic formation of H₃O⁺ causes the entire irradiated volume to temporarily become very acidic. The magnitude and duration of this abrupt “acid-spike” response depend on the value of <i>N</i>. It is most intense at times less than ~10–100 ns, equal to ~3.4 and 2.8 for <i>N</i> = 500 and 2000 (<i>i.e.</i>, for dose rates of ~1.9 × 10⁹ and 8.7 × 10⁹ Gy/s, respectively). At longer times, the pH gradually increases for all <i>N</i> values and eventually returns to the neutral value of seven, which corresponds to the non-radiolytic, pre-irradiation concentration of H₃O⁺. It is worth noting that these early acidic pH responses are very little dependent on the presence or absence of oxygen. Finally, given the importance of pH for many cellular functions, this study suggests that these acidic pH spikes may contribute to the normal tissue-sparing effect of FLASH radiotherapy.

FLASH radiotherapy is a new irradiation method in which large doses of ionizing radiation are delivered to tumors almost instantly (a few milliseconds), paradoxically sparing healthy tissue while preserving anti-tumor activity. Although this technique is primarily studied in the context of electron and photon therapies, proton delivery at high dose rates can also reduce the adverse side effects on normal cells. So far, no definitive mechanism has been proposed to explain the differences in the responses to radiation between tumor and normal tissues. Given that living cells and tissues consist mainly of water, we set out to study the effects of high dose rates on the radiolysis of water by protons in the energy range of 150 keV – 500 MeV (i.e., for linear energy transfer (LET) values between ∼72.2 and 0.23 keV/μm, respectively) using Monte Carlo simulations. To validate our methodology, however, we, first, report here the results of our calculations of the yields (G values) of the radiolytically produced species, namely the hydrated electron ([Formula: see text]), •OH, H•, H2, and H2O2, for low dose rates. Overall, our simulations agree very well with the experiment. In the presence of oxygen, [Formula: see text] and H• atoms are rapidly converted into superoxide anion or hydroperoxyl radicals, with a well-defined maximum of [Formula: see text] at ∼1 μs. This maximum decreases substantially when going from low-LET 500 MeV to high-LET 150 keV irradiating protons. Differences in the geometry of the proton track structure with increasing LET readily explain this diminution in [Formula: see text] radicals.

No abstract

Monte Carlo multi-track chemistry simulations were carried out to study, from a radiation chemistry perspective, the effect of “linear energy transfer” (LET) on the transient yields and concentrations of radiolytic oxygen consumption in the high dose-rate (~10⁷ Gy/s) radiolysis of both pure air-saturated (0.25 mM O₂) and oxygenated (30 µM O₂) cell water, in the interval ~1 ps–10 µs. Our simulation model consisted of randomly irradiating water with single pulses of 5-MeV (LET ~ 8 keV/µm), 1.5-MeV (LET ~ 19.5 keV/µm), and 0.7-MeV (LET ~ 33 keV/µm) protons at 25 °C. Similar to what is observed with low-LET irradiation (~300-MeV protons, LET ~ 0.3 keV/µm), our calculations showed that, in pure aerated water, the concentration of depleted oxygen, [–O₂], exhibits a pronounced maximum around ~0.1–0.2 μs for all three high-LET irradiating protons studied. This maximum increased markedly with increasing LET. As expected, the effect of adding competing scavengers of both hydrated electrons and •OH radicals on the radiolytic O₂ depletion in oxygenated cell water (a more bio-mimetic model of cells) irradiated by 5-MeV protons delivered at the same dose rate led to a marked decrease in the maximum of [–O₂] around 1 μs. However, contrary to what is observed for low-LET irradiation, we found that the transient O₂ consumption is quite substantial under high-LET irradiation conditions. This is explained by the fact that, even though their underlying mechanism of action differs, high-LET particles affect radiolysis yields in a similar way to high dose rates.