Linear energy transfer dependence of transient yields in water irradiated by 150 keV – 500 MeV protons in the limit of low dose rates

Abstract

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.

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

“…was chosen to ensure only minor statistical fluctuations (less than a few percent) in the calculated average chemical yields while maintaining acceptable computer time limits. with 60 Co  rays or fast electrons in the limit of low dose rates (i.e., without interaction between the different incident tracks); 52 as previously shown, 16,27 these data agree very well with measured H 3 O + yields at ambient temperature and are used here as a reference. Using our previous calibration 42 of N in terms of dose rate, 65 and G(OH  ) initially remain unchanged, regardless of N, until a critical time is reached, after which the various yield curves begin to deviate from their respective one-single proton irradiation (N = 1) reference curves.…”

“…This situation is very similar to the one we have been dealing with for many years in Monte Carlo simulations of the radiolysis of water in the limit of low dose rate, 15,52 only that instead of simulating a single-proton track, we simulate N interactive tracks at the same time. Under these conditions, the effect of the dose rate is studied by simply varying N.…”

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

“…Because this cylindrical volume is embedded in non-irradiated bulk water, the radiolytic species which initially form there are not restricted to this volume, but diffuse throughout the solution (infinite in fact) over time. In the end, this situation turns out to be essentially similar to the one we had to deal with previously in our Monte Carlo simulations of the radiolysis of water, including that of Fricke-cystamine solutions (in the absence of dose-rate effects) [ 4 , 6 , 21 , 48 ], except that here, instead of simulating a single-proton track at a time, N interactive tracks are simulated simultaneously.…”

Radical Production with Pulsed Beams: Understanding the Transition to FLASH

“…Moreover, in these simulations, the radiolytic oxygen consumption decreased with increasing oxygen concentration and dose rate, in line with experimental data. In contrast, other recent computational studies still support the ROD hypothesis [ 28 ], some considering other variables, such as the distribution of capillaries in tissues [ 29 ].…”