Generation of ultrafast, transient, highly acidic pH spikes in the radiolysis of water at very high dose rates: relevance for FLASH radiotherapy

Abstract

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 N 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 N. 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 N. It is most intense at times less than ∼10–100 ns, equal to ∼3.4 and 2.8 for N = 500 and 2000 (i.e., for dose rates of ∼1.9 × 109 and 8.7 × 109 Gy/s, respectively). At longer times, the pH gradually increases for all N 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.