Performance of SiC Diodes at Very High Doses of Low-Energy Proton Beams Under FLASH Conditions

Design and validation of an integrated reference dosimetry and monitoring system for ultra-high dose-rate proton beams ranging from 20 Gy/s to 230 Gy/s.

FLASH radiotherapy appears to kill off tumor cells while sparing healthy tissues, by irradiation at ultra high dose rate (>40 Gy s−1). The present study aims to clarify the mechanism of the sparing effect by proton irradiation under the FLASH conditions from a viewpoint of radiation chemistry. To do so, we evaluate radiation chemical yields (G values) of 7-hydroxy-coumarin-3-carboxylic acid (7OH–C3CA), which is produced by water radiolysis using coumarin-3-carboxylic acid (C3CA) solution as a radical scavenger of hydroxyl radicals. We shoot 27.5 MeV protons in the dose rate ranging from 0.05 to 160 Gy s−1. The recombination process of hydroxyl radicals produced is followed by varying the concentration of C3CA from 0.2 to 20 mM, which corresponds to the scavenging time scale from 7.1 to 714 ns. The G value of 7OH–C3CA produced decreases with increasing dose rate on the same scavenging time scale. Additionally, the trend of the relative G value normalized at a scavenging time scale of 100 ns, where radical–radical reaction subsides, is consistent in the examined dose rate range. This finding implies that G values of 7OH–C3CA produced reduce with increasing dose rate due to the oxygen depletion. We experimentally present that the sparing effect for healthy tissues would be seen even with a proton beam under the FLASH conditions due to the depletion of oxygen.

The ARRONAX cyclotron facility offers the possibility to deliver proton beams from low to ultra-high dose rates (UHDR). As a good control of the dosimetry is a prerequisite of UHDR experimentations, we evaluated in different conditions the usability and the dose rate dependency of several radiochromic films commonly used for dosimetry in radiotherapy. We compared the dose rate dependency of three types of radiochromic films: GAFchromic™ EBT3 and GAFchromic™ EBT-XD (Ashland Inc., Wayne, NJ, USA), and OrthoChromic OC-1 (OrthoChrome Inc., Hillsborough, NJ, USA), after proton irradiations at various mean dose rates (0.25, 40, 1500, and 7500Gy/s) and for 10 doses (2-130Gy). We also evaluated the dose rate dependency of each film considering beam structures, from single pulse to multiple pulses with various frequencies. EBT3 and EBT-XD films showed differences of response between conventional (0.25Gy/s) and UHDR (7500Gy/s) conditions, above 10Gy. On the contrary, OC-1 films did not present overall difference of response for doses except below 3Gy. We observed an increase of the netOD with the mean dose rate for EBT3 and EBT-XD films. OC-1 films did not show any impact of the mean dose rate up to 7500Gy/s, above 3Gy. No difference was found based on the beam structure, for all three types of films. EBT3 and EBT-XD radiochromic films should be used with caution for the dosimetry of UHDR proton beams over 10Gy. Their overresponse, which increases with mean dose rate and dose, could lead to non-negligible overestimations of the absolute dose. OC-1 films are dose rate independent up to 7500Gy/s in proton beams. Films response is not impacted by the beam structure. A broader investigation of the usability of OC-1 films in UHDR conditions should be conducted at intermediate and higher mean dose rates and other beam energies.

Calibration of MTT assay in proton beams using radiochromic films.

Background: In order to determine the relative biological effectiveness (RBE) of protons with high accuracy, radiobiological experiments with detailed knowledge of the linear energy transfer (LET) are needed. Cell survival data from high LET protons are sparse and experiments with low energy protons to achieve high LET values are therefore required. The aim of this study was to quantify LET distributions from a low energy proton beam by using Monte Carlo (MC) simulations, and to further compare to a proton beam representing a typical minimum energy available at clinical facilities.Materials and methods: A Markus ionization chamber and Gafchromic films were employed in dose measurements in the proton beam at Oslo Cyclotron Laboratory. Dose profiles were also calculated using the FLUKA MC code, with the MC beam parameters optimized based on comparisons with the measurements. LET spectra and dose-averaged LET (LETd) were then estimated in FLUKA, and compared with LET calculated from an 80 MeV proton beam.Results: The initial proton energy was determined to be 15.5 MeV, with a Gaussian energy distribution of 0.2% full width at half maximum (FWHM) and a Gaussian lateral spread of 2 mm FWHM. The LETd increased with depth, from approximately 5 keV/μm in the entrance to approximately 40 keV/μm in the distal dose fall-off. The LETd values were considerably higher and the LET spectra were much narrower than the corresponding spectra from the 80 MeV beam.Conclusions: MC simulations accurately modeled the dose distribution from the proton beam and could be used to estimate the LET at any position in the setup. The setup can be used to study the RBE for protons at high LETd, which is not achievable in clinical proton therapy facilities.

Objective. This work aims at characterizing LiF:Mg,Ti thermoluminescence detectors (TLDs) for dosimetry of a 250 MeV proton beam delivered at ultra-high dose rates (UHDR). Possible dose rate effects in LiF:Mg,Ti, as well as its usability for dosimetry of narrow proton beams are investigated. Approach. LiF:Mg,Ti (TLD-100TM Microcubes, 1 mm × 1 mm × 1 mm) was packaged in matrices of 5 × 5 detectors. The center of each matrix was irradiated with single-spot low-LET (energy >244 MeV) proton beam in the (1–4500) Gy s−1 average dose rates range. A beam reconstruction procedure was applied to the detectors irradiated at the highest dose rate (Gaussian beam sigma <2 mm) to correct for volumetric averaging effects. Reference dosimetry was carried out with a diamond detector and radiochromic films. The delivered number of protons was measured by a Faraday cup, which was employed to normalize the detector responses. Main results. The lateral beam spread obtained from the beam reconstruction agreed with the one derived from the radiochromic film measurements. No dose rates effects were observed in LiF:Mg,Ti for the investigated dose rates within 3% (k = 1). On average, the dose response of the TLDs agreed with the reference detectors within their uncertainties. The largest deviation (−5%) was measured at 4500 Gy s−1. Significance. The dose rate independence of LiF:Mg,Ti TLDs makes them suitable for dosimetry of UHDR proton beams. Additionally, the combination of a matrix of TLDs and the beam reconstruction can be applied to determine the beam profile of narrow proton beams.

Most codes of practice for dosimetry of proton beams do not give a clear recommendation on the determination of recombination correction factors for ionization chambers. In this work, recombination corrections were measured in the low-energy clinical proton beam of the Clatterbridge Centre of Oncology (CCO) using data collected at different dose rates and different polarizing voltages. This approach allows the separation of contributions from initial and volume recombination and was compared with results from extrapolation and two-voltage methods. A modified formulation of the method is presented for a modulated beam in which the ionization current is time dependent. Using a set-up with two identical chambers placed face-to-face yielded highly accurate data for plane-parallel ionization chambers. This method may also be used for high-energy photon and electron beam dosimetry. At typical dose rates of 26 Gy min−1 used clinically at the CCO, the recombination correction is 0.8% and thus is of importance for reference dosimetry. The proton beam should be treated as purely continuous given the high pulse repetition frequency of the cyclotron beam. The results show that the volume recombination parameter for protons is consistent with values measured for photon beams. Initial recombination was found to be independent of beam quality, except for a tendency to increase at the distal edge of the Bragg peak; this is only relevant for depth dose measurements. Using a general equation for recombination and generic values for the initial and volume recombination parameters (A = 0.25 V and m2 = 3.97 × 103 s cm−1 nC−1 V2), the experimental results are reproduced within 0.1% for all conditions met in this work. For the CCO beam and similar proton beams used for treating optical targets operating at high dose rates, the recombination correction factor can be overestimated by up to 2%, resulting in an overestimation of dose to water by the same amount, if the recommendation from IAEA TRS-398, which is only valid for pulsed beams, is followed without consideration.

Proceedings to the 7th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA)

Objective. The objective of this study was to investigate the impact of mean and instantaneous dose rates on the production of reactive oxygen species (ROS) during ultra-high dose rate (UHDR) radiotherapy. The study aimed to determine whether either dose rate type plays a role in driving the FLASH effect, a phenomenon where UHDR radiotherapy reduces damage to normal tissues while maintaining tumor control. Approach. Assays of hydrogen peroxide (H2O2) production and oxygen consumption (ΔpO2) were conducted using UHDR electron irradiation. Aqueous solutions of 4% albumin were utilized as the experimental medium. The study compared the effects of varying mean dose rates and instantaneous dose rates on ROS yields. Instantaneous dose rate was varied by changing the source-to-surface distance (SSD), resulting in instantaneous dose rates ranging from 102 to 106 Gy s−1. Mean dose rate was manipulated by altering the pulse frequency of the linear accelerator (linac) and by changing the SSD, ranging from 0.14 to 1500 Gy s−1. Main results. The study found that both ΔH2O2 and ΔpO2 decreased as the mean dose rate increased. Multivariate analysis indicated that instantaneous dose rates also contributed to this effect. The variation in ΔpO2 was dependent on the initial oxygen concentration in the solution. Based on the analysis of dose rate variation, the study estimated that 7.51 moles of H2O2 were produced for every mole of O2 consumed. Significance. The results highlight the significance of mean dose rate as a predictor of ROS production during UHDR radiotherapy. As the mean dose rate increased, there was a decrease in oxygen consumption and in H2O2 production. These findings have implications for understanding the FLASH effect and its potential optimization. The study sheds light on the role of dose rate parameters and their impact on radiochemical outcomes, contributing to the advancement of UHDR radiotherapy techniques.

The metal radionuclides <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">60</sup> Cu (T <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sub> = 23 min), <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">52</sup> mMn (T <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sub> = 21 min) and <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">94</sup> mTc (T <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sub> = 53 min) can be used to label tracers of high clinical and preclinical interest in PET studies. Furthermore, as they emit prompt gamma-rays right after the positron emission, they can be distinguished from standard positron emitters like <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">18</sup> F, enabling multiplexed PET (mPET) imaging. In this work we studied the feasibility of their production using a relatively low-energy (10 MeV) proton beam from a linear accelerator. These radionuclides were produced by bombardment on target foils of natural Nickel, Chromium and Molybdenum respectively. After activation, the emissions from the foils were analyzed by a Ge spectrometer and the absolute activity for each produced species was obtained. The activity generated was in agreement with the expected cross-sections and the isotopes present in the samples. These results The metal radionuclides <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">60</sup> Cu (T <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sub> = 23 min), <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">52</sup> mMn (T <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sub> = 21 min) and <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">94</sup> mTc (T <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sub> = 53 min) can be used to label tracers of high clinical and preclinical interest in PET studies. Furthermore, as they emit prompt gamma-rays right after the positron emission, they can be distinguished from standard positron emitters like <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">18</sup> F, enabling multiplexed PET (mPET) imaging. In this work we studied the feasibility of their production using a relatively low-energy (10 MeV) proton beam from a linear accelerator. These radionuclides were produced by bombardment on target foils of natural Nickel, Chromium and Molybdenum respectively. After activation, the emissions from the foils were analyzed by a Ge spectrometer and the absolute activity for each produced species was obtained. The activity generated was in agreement with the expected cross-sections and the isotopes present in the samples. These results show the feasibility of production of these radionuclides with a 10 MeV proton beam.show the feasibility of production of these radionuclides with a 10 MeV proton beam.

Low energy ion beam monitoring system by dosimetry film and particle induced X-ray

Proton beam is useful to target tumor tissue sparing normal cells by allowing precise dose only into tumor cells. However, the cellular and molecular mechanisms by which proton beam induces tumor cell death are still undefined. We irradiated three different tumor cells (LLC, HepG2, and Molt-4) with low energy proton beam (35 MeV) with spread out Bragg peak (SOBP) in vitro, and investigated cell death by MTT or CCK-8 assay at 24 h after irradiation. LLC and HepG2 cells were sensitive to proton beam at over 10 Gy to induce apoptosis whereas Molt-4 showed rather low sensitivity. Relative biological effectiveness (RBE) values for the death rate relative to gamma-ray were ranged from 1.1 to 2.3 in LLC and HepG2 but from 0.3 to 0.7 in Molt-4 at 11 d after irradiation by colony formation assay. The typical apoptotic nuclear DNA morphological pattern was observed by staining with 4'-6-diamidino-2-phenylindole (DAPI). Tiny fragmented DNA was observed in HepG2 but not in Molt-4 by the treatment of proton in apoptotic DNA fragment assay. By FACS analysis after stained with FITC-Annexin-V, early as well as median apoptotic fractions were clearly increased by proton treatment. Proton beam-irradiated tumor cells induced a cleavage of poly (ADP-ribose) polymerase-1 (PARP-1) and procaspases-3 and -9. Activity of caspases was highly enhanced after proton beam irradiation. Reactive oxygen species (ROS) were significantly increased and N-acetyl cysteine pretreatment restored the apoptotic cell death induced by proton beam. Furthermore, p38 and JNK but not ERK were activated by proton and dominant negative mutants of p38 and JNK revived proton-induced apoptosis, suggesting that p38 and JNK pathway may be activated through ROS to activate apoptosis. In conclusion, our data clearly showed that single treatment of low energy proton beam with SOBP increased ROS and induced cell death of solid tumor cells (LLC and HepG2) in an apoptotic cell death program by the induction of caspases activities.

Experimental study for the production cross sections of positron emitters induced from 12C and 16O nuclei by low-energy proton beams

As part of a continuing program of beam-plasma interaction studies, a low energy (2–10 keV) proton beam will be injected on a helical trajectory into a trapped electron plasma in a 1.6 T cryogenic solenoid. The proton source is a conventional duoplasmatron, but operated well below its design extraction energy. Beam tests over the desired energy range have established a mode with submillimeter beam focus and currents of a few μA. The beam will be transported into the high field, displaced, and then inflected by a sudden impulse onto an offset helical trajectory of low pitch. The electron plasma trapping potential will provide a fine pitch control and will serve as an analyzer of the residual longitudinal momentum (helix pitch). Previous experiments in this laboratory employing proton beams of high energy (50–300 MeV) in a storage ring have shown that an electron plasma absorbs angular momentum and energy from the proton beam-for example exhibiting expansion through beam misalignment which breaks the trap a...

Low energy protons in several keV energy range have very limited penetration depths into polymer films. This necessitates uses of very thin oxygen etch barrier layers and of dry image developments in oxygen reactive ion etching. For negative tone images the etch barrier layers were deposited patternwise in proton beam induced polymerizations of organo-metallic compounds, followed by dry image developments in oxygen reactive ion etching. For positive tone images the etch barrier layers were deposited prior to patternwise exposures to proton beams on top of polymer films by plasma polymerizations of organo-metallic compounds, or by evaporation or sputtering of certain metals. Hydrogen atoms and/or protons react with metal atoms in the etch barrier layers to yield volatile metal hydrides, making the exposed areas more vulnerable to oxygen reactive ion etching, and providing positive tone images after image developments. In these processes almost any kind of carbonaceous polymer films can be used as imaged materials. With a bright ion source available the exposure times could be less than a second, yielding high aspect ratio and high resolution polymer patterns.