MeV Proton Beam Research Articles

Clinical evaluation of performance, stability, and longevity of an accelerator system designed for boron neutron capture therapy utilising a beryllium target.

Boron neutron capture therapy for recurrent head and neck cancer has been approved as an insurance covered treatment in Japan since June 2020. The Kansai BNCT Medical Center has installed the NeuCure® BNCT system developed by Sumitomo Heavy Industries. This system utilises a beryllium target with a 30 MeV proton beam to generate neutrons. To date, the center has treated over 300 patients and the system is also used for quality control and fundamental research experiments. Information on the stability and longevity of the system is important for facilities and hospitals considering installation of a BNCT system in the future, particularly after an exchange of a major component, such as the target. The beam output (neutron and gamma ray) was measured before and after the exchange of the target. The thermal neutron, fast neutron and gamma ray distribution inside a water phantom was evaluated and the results showed no significant change in the beam quality after the exchange of the target. Furthermore, no significant change in the neutron flux as a function of increasing number of accumulated protons on the target was observed up to a value of just under 400 mAh. The NeuCure® BNCT system has been shown to be highly stable and the frequency of target replacement was much less than lithium target-based accelerators.

Performance of a BeO-based dosimetry system for proton and electron beam dose measurements

This study aims to evaluate the performance of the BeO-based myOSLchip system (RadPro International GmbH, Remscheid, Germany) for dosimetry of proton and electron radiotherapy beams. Although beryllium oxide (BeO) has been recognised as a promising material for luminescence dosimetry in radiotherapy, this research extends beyond material properties and examines the entire BeO-based dosimetry system, including the detector, holder, and readout components.Packages of myOSLchip dosimeters were irradiated either in a (70−230) MeV proton beam or in a 16 MeV electron beam. The readouts were carried out using the portable myOSLchip reader. In the electron beam, tests on the precision, dose response up to 100 Gy and dose-rate effects of the system were carried out. In the proton beam, the system was tested for its dose response (up to 10 Gy), fading, and linear energy transfer (LET) response.For proton irradiations, the myOSLchip BeO OSLDs exhibited stability within 2% over 135 days, as well as a linear dose response in the tested range, (0.1−10) Gy. The efficiency showed a reduction for proton beams with LET values (for water) above 0.6 keV/μm, with up to 40% loss in efficiency at 4 keV/μm. For the electron irradiations, they showed a linear dose–response up to 20 Gy and dose-rate independence, with a constant response at least up to 2.99 × 105 Gy s−1. Using individual dosimeter sensitivity correction, the precision for a single dosimeter was around 3.5% (standard deviation of the data of all dosimeters) and for a package comprising four dosimeters was 1.7% (standard deviation of the mean of the four dosimeters).These findings suggest the myOSLchip system’s potential as a reliable alternative to existing dosimetry systems in clinical applications.

Production cross sections of 102mRh and 108mAg in proton bombed natPb target with 400 MeV energy

The accelerator-driven subcritical system (ADS) is a competitive option for next-generation nuclear energy systems. Production cross sections of long-lived residual radioactive nuclides in a proton-nuclide reaction are basic quantities for the calculation of accumulated radioactivity in the use of ADS systems. This work presents the production cross sections of 102mRh and 108mAg in a natural lead (natPb) target activated by 400 MeV protons. The natPb target was irradiated by a 400 MeV proton beam in NRC “Kurchatov Institute” and measured two decades later by a low background gamma spectrometer in China Jinping Underground Laboratory (CJPL). A spectrum analysis method based on simulated single-isotope spectrum and Bayesian peak fitting was employed to compute the activities and production cross sections of the residual nuclides. The experimentally measured cross-sections for 102mRh and 108mAg were 0.72 ± 0.05 mb and 0.76 ± 0.09 mb respectively. These values are approximately twice as high as those predicted by the QGSP_INCLXX_HP model and fall within the range predicted by the INCL4+ABLA and LAQGSM+GEM2 models for mass numbers A=102 and A=108. These findings offer new experimental insights for ADS research and provide a practical benchmark for theoretical models concerning proton-lead interactions.

Total Ionizing Dose and Single-Event Effect Response of the AD524CDZ Instrumentation Amplifier

This manuscript focuses on studying the radiation response of the Commercial-off-the-shelf (COTS) AD524CDZ operational amplifier. Total Ionizing Dose (TID) effects were tested using low-dose 60Co irradiation. Single-Event Effect (SEE) sensitivity was studied on this operational amplifier using a 105 MeV proton beam. Additionally, further study of the SEE response was carried out using a Two-photon absorption laser to scan some sensitive sectors of the die. For this laser experiment, different gain setups and laser energies were employed to determine how the Single Event Transient (SET) response of the device was affected based on the test configuration. The results from the TID experiments revealed that the studied device remained functional after 100 krads (Si). Proton experiments revealed the studied device exhibited a high SET response with a maximum DC offset SET of about 1.5 V. Laser experiments demonstrated that there was a clear SET reduction when using 10× and 1000× gain setups.

Monitoring electron and proton beam profiles with segmented silicon sensors

The FRIDA INFN project characterized thin silicon sensors for monitoring electron FLASH beams, showing a response linearity up to ∼10 Gy/pulse on 9 MeV electrons. The use of segmented silicon configurations could provide the spatial resolution useful in Spatially Fractionated Radiotherapy (SFRT). Within the MIRO INFN project, a strip sensor integrated with a multichannel readout chip is being developed and tested for monitoring FLASH and SFRT electron and proton beams. One hundred and twenty-eight strips are independently read by two front-end TERA chips. Preliminary tests were performed on 6–10 MeV electron beams at the LINAC at Physics Department of the University of Torino, with and without using a tungsten minibeam collimator, and on 62–226 MeV proton beams at CNAO (Pavia). The capability to spatially resolve electron and proton beams at conventional dose-rates has been proved.

Development of a proton CT imaging system using scintillator-based range detection.

The accuracy of proton therapy and preclinical proton irradiation experiments is susceptible to proton range uncertainties, which partly stem from the inaccurate conversion between CT numbers and relative stopping power (RSP). Proton computed tomography (PCT) can reduce these uncertainties by directly acquiring RSP maps. This study aims to develop a novel PCT imaging system based on scintillator-based proton range detection for accurate RSP reconstruction. The proposed PCT system consists of a pencil-beam brass collimator with a 1mm aperture, an object stage capable of translation and 360° rotation, a plastic scintillator for dose-to-light conversion, and a complementary metal oxide semiconductor (CMOS) camera for light distribution acquisition. A calibration procedure based on Monte Carlo (MC) simulation was implemented to convert the obtained light ranges into water equivalent ranges. The water equivalent path lengths (WEPLs) of the imaged object were determined by calculating the differences in proton ranges obtained with and without the object in the beam path. To validate the WEPL calculation, measurements of WEPLs for eight tissue-equivalent inserts were conducted. PCT imaging was performed on a custom-designed phantom and a mouse, utilizing both 60 and 360 projections. The filtered back projection (FBP) algorithm was employed to reconstruct the RSP from WEPLs. Image quality was assessed based on the reconstructed RSP maps and compared to reference and simulation-based reconstructions. The differences between the calibrated and reference ranges of 110-150 MeV proton beams were within 0.18mm. The WEPLs of eight tissue-equivalent inserts were measured with accuracies better than 1%. Phantom experiments exhibited good agreement with reference and simulation-based reconstructions, demonstrating average RSP errors of 1.26%, 1.38%, and 0.38% for images reconstructed with 60 projections, 60 projections after penalized weighted least-squares algorithm denoising, and 360 projections, respectively. Mouse experiments provided clear observations of mouse contours and major tissue types. MC simulation estimated an imaging dose of 3.44 cGy for decent RSP reconstruction. The proposed PCT imaging system enables RSP map acquisition with high accuracy and has the potential to improve dose calculation accuracy in proton therapy and preclinical proton irradiation experiments.

Real-Time Radiation Beam Monitoring by Flexible Perovskite Thin Film Arrays.

Real-time and in-line transversal monitoring of ionizing radiation beams is a crucial task for several applications which span from medical treatments to particle accelerators in high energy physics. Here a flexible and large area device based on 2D hybrid perovskite thin films (phenylethylammonium lead bromide), fabricated onto a thin flexible polyimide substrate, able to map the transversal beam profile of high energy radiation beams is reported. The performance of this novel tool is here compared with the one offered by standard commercial large-area technology, namely radiochromic sheets. The great potential of this class of devices is demonstrated by successfully mapping in real-time a 5 MeV proton beam at fluxes between 108 and 1010 H+s-1 cm-2, confirming the capability to operate in a radiation-harsh environment without output signal saturation issues. The versatility and scalability of here proposed detecting system are demonstrated by the development of a multipixel array able to map in real-time a 40 kVp X-ray beam spot (dose rate 8 mGy s-1). Perovskite thin film-based detectors are thus assessed as a very promising class of thin, flexible devices for real-time, in-line, large-area, conformable, reusable, transparent, and low-cost transversal beam monitoring of different ionizing radiation.

Investigation of linear energy transfer (LET)-dependence behavior and dosimetric response of a flat-panel detector in pencil beam scanning proton therapy

PurposeThis study aims to elucidate the dependence of the flat-panel detector’s response on the linear energy transfer (LET) and evaluate the practical viability of employing flat-panel detectors in proton dosimetry applications through LET-dependent correction factors. MethodsThe study assessed the flat-panel detector’s response across varying depths using solid water and distinct 100, 150, and 200 MeV proton beams by comparing the flat-panel readings against reference doses measured with an ionization chamber. A Monte Carlo code was used to derive LET values, and an LET-dependent response correction factor was determined based on the ratio of the uncorrected flat-panel dose to the ionization chamber dose. The implications of this under-response correction were validated by applying it to a measurement involving a spread-out Bragg peak (SOBP), followed by a comparative analysis against doses calculated using the Monte Carlo code and MatriXX ONE measurement. ResultsThe association between LET and the flat-panel detector’s under-response displayed a positive correlation that intensified with increasing LET values. Notably, with a 10 keV/µm LET value, the detector’s under-response reached 50 %, while the measurement points in the SOBP demonstrated under-response greater than 20 %. However, post-correction, the adjusted flat-panel profile closely aligned with the Monte Carlo profile, yielding a 2-dimensional 3 %/3mm gamma passing rate of 100 % at various verification depths. ConclusionThis study successfully defined the link between LET and the responsiveness of flat-panel detectors for proton dosimetric measurements and established a foundational framework for integrating flat-panel detectors in clinical proton dosimetry applications.

Boron Nanoparticle-Enhanced Proton Therapy: Molecular Mechanisms of Tumor Cell Sensitization.

Boron-enhanced proton therapy has recently appeared as a promising approach to increase the efficiency of proton therapy on tumor cells, and this modality can further be improved by the use of boron nanoparticles (B NPs) as local sensitizers to achieve enhanced and targeted therapeutic outcomes. However, the mechanisms of tumor cell elimination under boron-enhanced proton therapy still require clarification. Here, we explore possible molecular mechanisms responsible for the enhancement of therapeutic outcomes under boron NP-enhanced proton therapy. Spherical B NPs with a mode size of 25 nm were prepared by methods of pulsed laser ablation in water, followed by their coating by polyethylene glycol to improve their colloidal stability in buffers. Then, we assessed the efficiency of B NPs as sensitizers of cancer cell killing under irradiation with a 160.5 MeV proton beam. Our experiments showed that the combined effect of B NPs and proton irradiation induces an increased level of superoxide anion radical generation, which leads to the depolarization of mitochondria, a drop in their membrane mitochondrial potential, and the development of apoptosis. A comprehensive gene expression analysis (via RT-PCR) confirmed increased overexpression of 52 genes (out of 87 studied) involved in the cell redox status and oxidative stress, compared to 12 genes in the cells irradiated without B NPs. Other possible mechanisms responsible for the B NPs-induced radiosensitizing effect, including one related to the generation of alpha particles, are discussed. The obtained results give a better insight into the processes involved in the boron-induced enhancement of proton therapy and enable one to optimize parameters of proton therapy in order to maximize therapeutic outcomes.

First independent validation of the proton-boron capture therapy concept

Boron has been suggested to enhance the biological effectiveness of proton beams in the Bragg peak region via the p + 11B → 3α nuclear capture reaction. However, a number of groups have observed no such enhancement in vitro or questioned its proposed mechanism recently. To help elucidate this phenomenon, we irradiated DU145 prostate cancer or U-87 MG glioblastoma cells by clinical 190 MeV proton beams in plateau or Bragg peak regions with or without 10B or 11B isotopes added as sodium mercaptododecaborate (BSH). The results demonstrate that 11B but not 10B or other components of the BSH molecule enhance cell killing by proton beams. The enhancement occurs selectively in the Bragg peak region, is present for boron concentrations as low as 40 ppm, and is not due to secondary neutrons. The enhancement is likely initiated by proton-boron capture reactions producing three alpha particles, which are rare events occurring in a few cells only, and their effects are amplified by intercellular communication to a population-level response. The observed up to 2–3-fold reductions in survival levels upon the presence of boron for the studied prostate cancer or glioblastoma cells suggest promising clinical applications for these tumour types.

Radiosensitization with metallic nanoparticles under MeV proton beams: local dose enhancement.

In addition to specific dosimetric properties of protons, their higher biological effectiveness makes them superior to X-rays and gamma radiation, in radiation therapy. In recent years, enrichment of tumours with metallic nanoparticles as radiosensitizer agents has generated high interest, with several studies attempting to confirm the efficacy of nanoparticles in proton therapy. In the present study Geant4 Monte Carlo (MC) code was used to quantify the increased nanoscopic dose deposition of 50nm metallic nanoparticles including gold, bismuth, iridium, and gadolinium in water upon exposure to 5, 25, and 50MeV protons. Dose enhancement factors, radial dose distributions in nano-scale, as well as secondary electron and photon energy spectra were calculated for the studied nanoparticles and proton beams. The obtained results demonstrated that in the presence of metallic nanoparticles an increase in proton energy leads to a decrease in secondary electron and photon production yield. Additionally, an increase in the radial dose enhancement factor from 1.4 to 16 was calculated for the studied nanoparticles when the proton energy was increased from 5 to 50MeV. It is concluded that the dosimetric advantages of proton beams could be improved significantly in the presence of metallic nanoparticles.

Bricks non-destructive simulation testing method utilizing neutron radiography facility based on a 7Li(p,n)7Be reaction

The evaluation of non-destructive neutron radiography (NR) for examining the internal composition of various structural materials, has been the focus of extensive research. This manuscript uses non-destructive testing to generate three-dimensional radiographs of three different brick structural materials: glass block, magnesia-chrome, and lead to evaluate their capability to withstand fast neutrons and gammas emitted from a source. When neutrons with thermal or epithermal spectrum are required, the optimum combination for an accelerator was simulated using a 2.8 MeV proton beam on a lithium target. The presented facility tested both thermal and fast neutron radiography. This study examined various aperture diameters and collimator lengths. It found that implementing a special fast neutron filter significantly increased the thermal neutron content (TNC) with minimal impact on the thermal neutron flux. For fast neutron radiography, the study evaluated parameters such as geometric unsharpness, fast neutron flux, and the percentage of the uncollided fast neutron reaching the object. Both neutrons and photons from the source were used to inspect faults in a glass brick.

Pressed Solid Target Production of 89Zr and its Application for Antibody Labelling.

Zirconium-89 ( 89Zr, t1/2=3.27d) is an important + emitting radionuclide used in Positron Emission Tomography (PET) immuno studies due to its unique characteristics and increased demand due to simple and cost-effective production capacity. Production of 89Zr is achieved primarily through solid natural yttrium targets via different target preparation methodologies, such as electrodeposition, pressed foils, and spark plasma sintering. In this study, we have investigated the pressed solid target methodology. The Yttrium Oxide (Y2O3) powder was pressed to pellet form and stacked over a different back support plate, such as platinum (Pt), niobium (Nb), and tantalum (Ta). The target was irradiated with approximately 12 MeV proton beam for 10-60 minutes at 20µA current. The irradiated target was purified through a solid phase extraction method via hydroxamate-based resin by manual or automatic approach. The purified 89Zr was analyzed using gamma scintigraphy, and specific activity was calculated through Deferoxamine (DFO) chelation. 89Zr radionuclide via pressed target was effectively produced with a production yield of 20-30 MBq/µA.h, and the purification was achieved in 35 minutes with (87.46)% average recovery and >98% purity while using automated purification, but manual purification took 2 hours with (91 ± 2)% recovery and >98% purity. The production yield was comparable to the reported pressed target approach. Deferoxamine (DFO) chelation with 89Zr-oxalate was performed with purity >98% and specific activity of 25-30 µCi/mmol. In this study, we explored the production of 89Zr by pressed targets and purification via manual or automated methods with good radionuclide purity. The chelation with DFO or its analog was performed with good labeling efficiency and stability</p>.

Chemical characterization of lithium based ceramics utilizing charged particle activation and ion beam techniques

Non-destructive methodologies using activation analysis and ion beam analysis techniques were optimized for the chemical characterization of ceramic materials, lithium titanate and lithium niobate, which have application in tritium breeding blanket. The analyses were carried out as a part of chemical quality control exercise. The atomic ratios of Li/Ti, Li/Nb were quantified by charged particle activation analysis using 13 MeV proton beam from variable energy cyclotron facility and particle induced gamma ray emission/Rutherford backscattering spectrometry using 3 MeV/2 MeV proton beam from 3MV tandem accelerator facility. The results of these different analytical methods are in good agreement, which established the applicability of these activation analysis and ion beam techniques for the chemical characterization of these ceramic materials.

Interplay of single-particle and collective modes in the 12C(p,2p) reaction near 100 MeV

The 12C(p,2p)11B reaction at Ep=98.7 MeV proton beam energy is analyzed using a rigorous three-particle scattering formalism extended to include the internal excitation of the nuclear core or residual nucleus. The excitation proceeds via the core interaction with any of the external nucleons. We assume the 11B ground and low-lying excited states [32− (0.0 MeV), 52− (4.45 MeV), 72− (6.74 MeV)] and the excited states [12− (2.12 MeV), 32− (5.02 MeV)] to be members of K=32− and K=12− rotational bands, respectively. The dynamical core excitation results in a significant cross section for the reaction leading to the 52− (4.45 MeV) excited state of 11B that cannot be populated through the single-particle excitation mechanism. The detailed agreement between the theoretical calculations and data depends on the used optical model parametrizations and the kinematical configuration of the detected nucleons.

Monte Carlo simulations of microdosimetry and radiolytic species production at long time post proton irradiation using GATE and Geant4-DNA.

Radiobiological effectiveness of radiation in cancer treatment can be studied at different scales (molecular till organ scale) and different time post irradiation. The production of free radicals and reactive oxygen species during water radiolysis is particularly relevant to understand the fundamental mechanisms playing a role in observed biological outcomes. The development and validation of Monte Carlo tools integrating the simulation of physical, physico-chemical and chemical stages after radiation is very important to maintain with experiments. Therefore, in this study, we propose to validate a new Geant4-DNA chemistry module through the simulation of water radiolysis and Fricke dosimetry experiments on a proton preclinical beam line. In this study, we used the GATE Monte Carlo simulation platform (version 9.3) to simulate a 67.5 MeV proton beam produced with the ARRONAX isochronous cyclotron (IBA Cyclone 70XP) at conventional dose rate (0.2Gy/s) to simulate the irradiation of ultra-pure liquid water samples and Fricke dosimeter. We compared the depth dose profile with measurements performed with a plane parallel Advanced PTW 34045 Markus ionization chamber. Then, a new Geant4-DNA chemistry application proposed from Geant4 version 11.2 has been used to assess the evolution of , , , , , , and reactive species along time until 1-h post-irradiation. In particular, the effect of oxygen and pH has been investigated through comparisons with experimental measurements of radiolytic yields for and Fe3+. GATE simulations reproduced, within 4%, the depth dose profile in liquid water. With Geant4-DNA, we were able to reproduce experimental radiolytic yields 1-h post-irradiation in aerated and deaerated conditions, showing the impact of small changes in oxygen concentrations on species evolution along time. For the Fricke dosimeter, simulated G(Fe3+) is 15.97±0.2 molecules/100eV which is 11% higher than the measured value (14.4±04 molecules/100 eV). These results aim to be consolidated by new comparisons involving other radiolytic species, such as or to further study the mechanisms underlying the FLASH effect observed at ultra-high dose rates (UHDR).

Measurement of production cross-sections of natTi(p,x)43K,43,44m,44g,46g,47,48Sc,48V reactions up to 50 MeV

The cross-sections of natTi(p,x) reactions were measured up to 50 MeV by using off-line γ-ray spectrometry and stacked-foil activation technique. The activation experiment was conducted using 57 MeV proton beams from the proton accelerator at the Korea Multi-purpose Accelerator Complex (KOMAC). The natNi(p,x)57Ni reaction was employed to monitor the proton beam flux. The activity of irradiated sample was measured using a high purity germanium (HPGe) detector, and the measured cross-sections were compared with literature data and the TENDL-2023 library. The present work generally matched well with the literature data. The cross-sections for 43,44,47Sc produced through the natTi(p,x) reactions can be used for medical isotopes production, while natTi(p,x)48V reaction can be utilized for proton monitoring reaction.

Design and thermal-hydraulic analysis of multi-target system with 100 MeV proton linear accelerator for the production of 67Cu and 68Ge radioisotopes

Radioisotopes are widely used in the fields of medicine, science, and industry. The growing demand for medical radioisotopes has driven research on alternative production methods. In particular, both isotopes of 67Cu and 68Ge play vital roles in the medical environment in many countries to be used in the radio-immunotherapy and the positron emission tomography imaging, respectively. This study designed a multi-target system consisting of two Zn and one Ga2O3 plates to enable simultaneous production of the medical radioisotopes 67Cu and 68Ge using 100 MeV proton beams. To understand the thermal effect on the multi-targets, we examined the distribution of energy absorbed in each solid plate target when exposed to an accelerated proton beam through the thermal-fluid analysis based on ANSYS simulation. For confirming thermal stability for two Zn targets and one Ga2O3 target, the modified water flow path inside the multi-target system was designed effectively with the controlled distribution of multiple sub-holes between main inlet and the following four channels. It was confirmed that the newly designed multi-target system of Zn and Ga2O3 solid plates shows higher thermal stability than the case of uniform distribution of water inlet, which means it could be exposed to a higher current beam of 7.57% to decrease the processing time.

In-beam PET monitoring of proton therapy: a method for filtering prompt radiation events

Objective. In-beam positron emission tomography (PET) is a promising technology for real-time monitoring of proton therapy. Random coincidences between prompt radiation events and positron annihilation photon pairs can deteriorate imaging quality during beam-on operation. This study aimed to improve the PET image quality by filtering out the prompt radiation events. Approach. We investigated a prompt radiation event filtering method based on the accelerator radio frequency phase and assessed its performance using various prompt gamma energy thresholds. An in-beam PET prototype was used to acquire the data when the 70 MeV proton beam irradiated a water phantom and a mouse. The signal-to-background ratio (SBR) indicator was utilized to evaluate the quality of the PET reconstruction image. Main results. The selection of the prompt gamma energy threshold will affect the quality of the reconstructed image. Using the optimal energy threshold of 580 keV can obtain a SBR of 1.6 times for the water phantom radiation experiment and 2.0 times for the mouse radiation experiment compared to those without background removal, respectively. Significance. Our results show that using this optimal threshold can reduce the prompt radiation events, enhancing the SBR of the reconstructed image. This advancement contributes to more accurate real-time range verification in subsequent steps.

Development of a cylindrical mirror analyser electron spectrometer and associated data acquisition system to study inner shell electron emission following ion-atom collision

In this paper we report on the development and performance of a cylindrical mirror analyser electron spectrometer for ion atom collision experiments. A low cost data acquisition system using Arduino microcontroller has also been developed and tested. We have measured the Auger emission spectra for various gaseous targets in collision with 1 MeV proton beams. Relative total Auger emission cross sections have also been measured for N2 molecular target as a function of incident proton energy. The projectile energy dependence agrees well with earlier reported measurements.