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 (H<sub>3</sub>O<sup>+</sup>) 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 H<sub>3</sub>O<sup>+</sup> 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 × 10<sup>9</sup> and 8.7 × 10<sup>9</sup> 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 H<sub>3</sub>O<sup>+</sup>. 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.

Early and Transient Formation of Highly Acidic pH Spikes in Water Radiolysis under the Combined Effect of High Dose Rate and High Linear Energy Transfer

“…In this work, we extend our Monte Carlo track chemistry simulations to study the effect of combining the action of both high absorbed dose rate and high-LET irradiations on the transient yields and concentrations of H 3 O + ions and the resulting acidic pH spikes that form early in water radiolysis, in relation to their potential relevance to the FLASH effect. The present study can thus be seen as a continuation of our previous work [21,22,36]. In a condensed phase such as liquid water, the radiolysis products (water cations H 2 O •+ , excited water H 2 O*, and all ejected secondary electrons) generated in the initial or "physical" stage (~1-100 as) of radiation action [45,46] are very energetically/chemically unstable and undergo a complex sequence of fast reactions and reorganization in the second or "physicochemical" stage (≤1 ps), leading to the formation of the very first reactive chemical species which include e − aq , [36,47].…”

“…Following water radiolysis at the prevailing ultrahigh FLASH dose rates (pulses of a fraction of a second), we previously demonstrated with Monte-Carlo-based simulations the existence of strongly acidic spikes which appear transiently over the entire irradiated volume immediately after the passage of the radiation [21,22]. Let us briefly recall here the origin of this acidity.…”

“…At the ultrahigh dose rates of FLASH-RT, the energy of the ionizing radiation can then be considered to be relatively uniformly distributed throughout the entire irradiated volume. As a result, the transient acid spikes around each radiation track combine due to their close physical proximity, thus producing an early acidic pH response across the whole solution [21,22].…”

Assessment of Cystamine’s Radioprotective/Antioxidant Ability under High-Dose-Rate Irradiation: A Monte Carlo Multi-Track Chemistry Simulation Study

“…We used a multi-track irradiation model [ 37 ], recently developed in our laboratory, to study the effects of high dose rates on low-LET water radiolysis at ambient [ 37 , 44 , 45 ] and elevated [ 46 ] temperatures. Briefly, this model consists of randomly irradiating water with single and instantaneous pulses of N 300-MeV incident protons which simultaneously penetrate this water perpendicularly inside the surface of a circle of a given radius (see Figure 1 ).…”

“…In order to simulate the high-dose-rate radiolysis of the studied aerated and deaerated Fricke-cystamine solutions at 25 °C by 300-MeV irradiating protons, we used an extended version of our Monte Carlo computer code IONLYS-IRT [ 21 , 49 , 50 ]. Since this version has been described in detail elsewhere [ 37 , 44 , 45 , 46 ], only a brief overview of its main features is given below.…”