(1) Background: Radioprotective agents have garnered considerable interest due to their prospective applications in radiotherapy, public health medicine, and situations of large-scale accidental ...radiation exposure or impending radiological emergencies. Cystamine, an organic diamino-disulfide compound, is recognized for its radiation-protective and antioxidant properties. This study aims to utilize the aqueous ferrous sulfate (Fricke) dosimeter to measure the free-radical scavenging capabilities of cystamine during irradiation by fast carbon ions. This analysis spans an energy range from 6 to 500 MeV per nucleon, which correlates with "linear energy transfer" (LET) values ranging from approximately 248 keV/μm down to 9.3 keV/μm. (2) Methods: Monte Carlo track chemistry calculations were used to simulate the radiation-induced chemistry of aerated Fricke-cystamine solutions across a broad spectrum of cystamine concentrations, ranging from 10
to 1 M. (3) Results: In irradiated Fricke solutions containing cystamine, cystamine is observed to hinder the oxidation of Fe
ions, an effect triggered by oxidizing agents from the radiolysis of acidic water, resulting in reduced Fe
ion production. Our simulations, conducted both with and without accounting for the multiple ionization of water, confirm cystamine's ability to capture free radicals, highlighting its strong antioxidant properties. Aligning with prior research, our simulations also indicate that the protective and antioxidant efficiency of cystamine diminishes with increasing LET of the radiation. This result can be attributed to the changes in the geometry of the track structures when transitioning from lower to higher LETs. (4) Conclusions: If we can apply these fundamental research findings to biological systems at a physiological pH, the use of cystamine alongside carbon-ion hadrontherapy could present a promising approach to further improve the therapeutic ratio in cancer treatments.
Large doses of ionizing radiation delivered to tumors at ultra-high dose rates (i.e., in a few milliseconds) paradoxically spare the surrounding healthy tissue while preserving anti-tumor activity ...(compared with conventional radiotherapy delivered at much lower dose rates). This new modality is known as “FLASH radiotherapy” (FLASH-RT). Although the molecular mechanisms underlying FLASH-RT are not yet fully understood, it has been suggested that radiation delivered at high dose rates spares normal tissue via oxygen depletion followed by subsequent radioresistance of the irradiated tissue. To date, FLASH-RT has been studied using electrons, photons, and protons in various basic biological experiments, pre-clinical studies, and recently in a human patient. However, the efficacy of heavy ions, such as energetic carbon ions, under FLASH-RT conditions remains unclear. Given that living cells and tissues consist mainly of water, we set out to study, from a pure radiation chemistry perspective, the effects of ultra-high dose rates on the transient yields and concentrations of radiolytic species formed in water irradiated by 300-MeV per nucleon carbon ions (LET ∼ 11.6 keV/µm). This mimics irradiation in the “plateau” region of the depth–dose distribution of ions, i.e., in the “normal” tissue region in which the LET is rather low. We used Monte Carlo simulations of multiple, simultaneously interacting radiation tracks together with an “instantaneous pulse” irradiation model. Our calculations show a pronounced oxygen depletion around 0.2 μs, strongly suggesting, as with electrons, photons, and protons, that irradiation with energetic carbon ions at ultra-high dose rates is suitable for FLASH-RT.
(1) Background: cystamine and its reduced form cysteamine have radioprotective/antioxidant effects in vivo. In this study, we use an in vitro model system to examine the behavior of cystamine towards ...the reactive primary species produced during the radiolysis of the Fricke dosimeter under high dose-rate irradiation conditions. (2) Methods: our approach was to use the familiar radiolytic oxidation of ferrous to ferric ions as an indicator of the radioprotective/antioxidant capacity of cystamine. A Monte Carlo computer code was used to simulate the multi-track radiation-induced chemistry of aerated and deaerated Fricke-cystamine solutions as a function of dose rate while covering a large range of cystamine concentrations. (3) Results: our simulations revealed that cystamine provides better protection at pulsed dose rates compared to conventional, low-dose-rate irradiations. Furthermore, our simulations confirmed the radical-capturing ability of cystamine, clearly indicating the strong antioxidant profile of this compound. (4) Conclusion: assuming that these findings can be transposable to cells and tissues at physiological pH, it is suggested that combining cystamine with FLASH-RT could be a promising approach to further enhance the therapeutic ratio of cancer cure.
The effect of temperature on the yields of H
2
and hydrated electrons (e
aq
−
) in the low linear energy transfer (LET) radiolysis of liquid water has been modeled by Monte Carlo track chemistry ...simulations using phenol/N
2
O aqueous solutions from 25 up to 350 °C. N
2
O was used to scavenge e
aq
−
and H&z.rad; atoms formed in spurs giving N
2
as a product. The primary aim of this work is to elucidate the main factors that account for the anomalous increase in the H
2
yield with temperature. Comparing our calculated H
2
and N
2
yields with experiments led us to re-evaluate certain parameters involved in radiolysis, such as the H
−
/H
2
O dissociative electron attachment (DEA) cross section and its variation with temperature. Most importantly, we found that the prompt DEA process largely dominates the temperature dependence of the primary yield of H
2
over most of the temperature range considered. Unlike what has been proposed by some authors in the literature, our simulations showed that the oxidation of water by H&z.rad; atoms contributes only ∼12% of the total
g
(H
2
) at 350 °C and is thus insufficient to quantitatively explain, by itself, the increase in
g
(H
2
) with temperature that is observed experimentally above 200 °C.
The effect of temperature on the yields of H
2
and hydrated electrons in the low linear energy transfer radiolysis of water has been modeled by Monte Carlo track chemistry simulations using phenol/N
2
O aqueous solutions from 25 up to 350 °C.
In the spirit of the radiation chemical "spur model", the lifetime of a spur (τ(s)) is an important indicator of overlapping spurs and the establishment of homogeneity in the distribution of reactive ...species created by the action of low linear energy transfer (LET) radiation (such as fast electrons or γ irradiation). In fact, τ(s) gives the time required for the changeover from nonhomogeneous spur kinetics to homogeneous kinetics in the bulk solution, thus defining the so-called primary (or "escape") radical and molecular yields of radiolysis, which are obviously basic to the quantitative understanding of any irradiated chemical system. In this work, τ(s) and its temperature dependence have been determined for the low-LET radiolysis of deaerated 0.4 M aqueous solutions of H(2)SO(4) and pure liquid water up to 350 °C using a simple model of energy deposition initially in spurs, followed by random diffusion of the species of the spur during track expansion until spur overlap is complete. Unlike our previous τ(s) calculations, based on irradiated Fricke dosimeter simulations, the current model is free from any effects due to the presence of oxygen or the use of scavengers. In acidic solutions, the spur lifetime values thus obtained are in very good agreement with our previous calculations (after making appropriate corrections, however, to account for the possibility of competition between oxygen and Fe(2+) ions for H˙ atoms in the Fricke dosimeter, an effect which was not included in our original simulations). In this way, we confirm the validity of our previous approach. As expected, in the case of pure, oxygen-free water, our calculated times required to reach complete spur overlap are essentially the same (within uncertainty limits) as those found in acidic solutions. This explicitly reflects the fact that the diffusion coefficients for the hydrated electron and the H˙ atom that are involved in the overall calculation of the lifetime of spurs in neutral or acidic media, respectively, are of similar magnitude over the 25-350 °C temperature range studied.
Meesungnoen, J. and Jay-Gerin, J-P. High-LET Ion Radiolysis of Water: Oxygen Production in Tracks. Radiat. Res. 171, 379–386 (2009). It is known that molecular oxygen is a product of the radiolysis ...of water with high-linear energy transfer (LET) radiation, a result that is of particular significance in radiobiology and of practical relevance in radiotherapy. In fact, it has been suggested that the radiolytic formation of an oxygenated microenvironment around the tracks of high-LET heavy ions is an important factor in their enhanced biological efficiency in the sense that this may be due to an “oxygen effect” by O2 produced by these ions in situ. Using Monte Carlo track simulations of pure, deaerated water radiolysis by 4.8 MeV 4He2+ (LET ∼ 94 keV/μm) and 24 MeV 12C6+ (LET ∼ 490 keV/μm) ions, including the mechanism of multiple ionization of water, we have calculated the yields and concentrations of O2 in the tracks of these irradiating ions as a function of time between ∼10−12 and 10−5 s at 25 and 37°C. The track oxygen concentrations obtained compare very well with O2 concentrations estimated from the “effective” amounts of oxygen that are needed to produce the observed reduction in oxygen enhancement ratio (OER) with LET (assuming this decrease is attributable to the sole radiolytic formation of O2 in the tracks). For example, for 24 MeV 12C6+ ions, the initial track concentration of O2 is estimated to be more than three orders of magnitude higher than the oxygen levels present in normally oxygenated and hypoxic tumor regions as well as in normal human cells. Such results, which largely plead in favor of the “oxygen in the heavy-ion track” hypothesis, could explain at least in part the greater efficiency of high-LET radiation for cell inactivation (at equal radiation dose).
The "spur lifetime" (τ(s)) in the low-linear energy transfer (LET) radiolysis of supercritical water (SCW) at 400 °C has been determined as a function of water density by using a simple model of ...energy deposition initially in spurs, followed by the random diffusion (Brownian motion) of the species formed until spur expansion is complete. The values of τ(s) are found to decrease from ∼5.0 × 10(-6) to 5.0 × 10(-8) s over the density range from 0.15 to 0.6 g cm(-3). Using Monte-Carlo simulations, our calculated density dependence of the "escape" hydrated electron (e(aq)(-)) yield (i.e., at time τ(s)) reproduces fairly well Bartels and co-workers' scavenged e(aq)(-) yield data, suggesting that these data may have been measured at times close to τ(s).
