Optimized beam shaping assembly for a 2.1-MeV proton-accelerator-based neutron source for boron neutron capture therapy.

Boron Neutron Capture Therapy (BNCT) is facing a new era where different projects based on accelerators instead of reactors are under development. The new facilities can be placed at hospitals and will increase the number of clinical trials. The therapeutic effect of BNCT can be improved if a optimized epithermal neutron spectrum is obtained, for which the beam shape assembly is a key ingredient. In this paper we propose an optimal beam shaping assembly suited for an affordable low energy accelerator. The beam obtained with the device proposed accomplishes all the IAEA recommendations for proton energies between 2.0 and 2.1 MeV. In addition, there is an overall improvement of the figures of merit with respect to BNCT facilities and previous proposals of new accelerator-based facilities.

A bi-tapered and air-gapped beam shaping assembly used for AB-BNCT.

The 7Li(p,n)7Be reaction, which leads to a soft neutron field, is often chosen as the neutron producing reaction used for accelerator-based boron neutron capture therapy (AB-BNCT). This study aims to design a compact beam shaping assembly (BSA) and auxiliary system for a 7Li(p,n)7Be reaction-based neutron source and to evaluate the relationship between the BSA design and the consequent neutron beam quality for further optimization. In this study, five types of moderator shapes for the BSA model were designed. Both the in-air and in-phantom figures of merit were considered to evaluate the performance of the BSA designs. It was found that the BSA with a bi-tapered and air-gapped design could generate a high-intensity epithermal neutron beam, which could be used to treat deep-seated brain tumors within a reasonable time.

The E LiBANS project: Thermal and epithermal neutron sources based on a medical Linac.

The E_LIBANS project (INFN) aims at producing neutron facilities for interdisciplinary irradiation purposes among which pre-clinical research for BNCT. After the successful setting-up of the thermal neutron source based on a medical LINAC, a similar apparatus for epithermal neutrons has been developed. Both structures are based on an Elekta 18 MV coupled with a photoconverter-moderator system which deploys the (γ,n) reaction to convert the X-rays into neutrons. This communication describes the two neutron sources and the results obtained in their characterization.

Simulation for improved collimation system of gamma-ray telescope system for boron neutron capture therapy at Kyoto University Reactor.

A gamma-ray telescope system has been used at Heavy Water Neutron Irradiation Facility at Kyoto University Reactor mainly for boron neutron capture therapy (BNCT) for multiple hepatic tumors. This system has been improved to accommodate BNCT for other sites, such as brain, head and neck, lung, breast, etc. Simulation for the collimation system was performed. It revealed that the effective telescope field-of-view could be expanded from approximately 3-21 cm.

Implications of radiation microdosimetry for accelerator-based boron neutron capture therapy: a radiobiological perspective.

Boron neutron capture therapy (BNCT) has great potential to selectively destroy cancer cells while sparing surrounding normal cells. The basic concept of BNCT was developed in the 1930s, but it has not yet been commonly used in clinical practice, even though there is now a large number of experimental and translational studies demonstrating its marked therapeutic potential. With the development of neutron accelerators that can be installed in medical institutions, accelerator-based BNCT is expected to become available at several medical institutes around the world in the near future. In this commentary, from the point of view of radiation microdosimetry, we discuss the biological effects of BNCT, especially the underlying mechanisms of compound biological effectiveness. Radiobiological perspectives provide insight into the effectiveness of BNCT in creating a synergy effect in the field of clinical oncology.

Microdosimetric quantities of an accelerator-based neutron source used for boron neutron capture therapy measured using a gas-filled proportional counter.

Boron neutron capture therapy (BNCT) is an emerging radiation treatment modality, exhibiting the potential to selectively destroy cancer cells. Currently, BNCT is conducted using a nuclear reactor. However, the future trend is to move toward an accelerator-based system for use in hospital environments. A typical BNCT radiation field has several different types of radiation. The beam quality should be quantified to accurately determine the dose to be delivered to the target. This study utilized a tissue equivalent proportional counter (TEPC) to measure microdosimetric and macrodosimetric quantities of an accelerator-based neutron source. The micro- and macro-dosimetric quantities measured with the TEPC were compared with those obtained via the the particle and heavy ion transport code system (PHITS) Monte Carlo simulation. The absorbed dose from events >20 keV/µm measured free in air for a 1-h irradiation was calculated as 1.31 ± 0.02 Gy. The simulated result was 1.41 ± 0.07 Gy. The measured and calculated values exhibit good agreement. The relative biological effectiveness (RBE) that was evaluated from the measured microdosimetric spectrum was calculated as 3.7 ± 0.02, similar to the simulated value of 3.8 ± 0.1. These results showed the PHITS Monte Carlo simulation can simulate both micro- and macro-dosimetric quantities accurately. The RBE was calculated using a single-response function, and the results were compared with those of several other institutes that used a similar method. However, care must be taken when using such a single-response function for clinical application, as it is only valid for low doses. For clinical dose ranges (i.e., high doses), multievent distribution inside the target needs to be considered.

Boron neutron capture therapy (BNCT): a unique role in radiotherapy with a view to entering the accelerator-based BNCT era.

Boron neutron capture therapy (BNCT) has a unique property of tumor-cell-selective heavy-particle irradiation. BNCT can form large dose gradients between cancer cells and normal cells, even if the two types of cells are mingled at the tumor margin. This property makes it possible for BNCT to be used for pre-irradiated locally recurrent tumors. Shallow-seated, locally recurrent lesions have been treated with BNCT because of the poor penetration of neutrons in the human body. BNCT has been used in clinical studies for recurrent malignant gliomas and head and neck cancers using neutron beams derived from research reactors, although further investigation is warranted because of the small number of patients. In the latter part of this review, the development of accelerator-based neutron sources is described. BNCT for common cancers will become available at medical institutes that are equipped with an accelerator-based BNCT system. Multiple metastatic lung tumors have been investigated as one of the new treatment candidates because BNCT can deliver curative doses of radiation to the tumors while sparing normal lung tissue. Further basic and clinical studies are needed to move toward an era of accelerator-based BNCT when more patients suffering from refractory cancers will be treated.

Design and construction of an accelerator-based boron neutron capture therapy (AB-BNCT) facility with multiple treatment rooms at the Southern Tohoku BNCT Research Center.

Installation of an accelerator-based boron neutron capture therapy (AB-BNCT) system was started in April 2014 at the Southern Tohoku BNCT Research Center (STBRC), and clinical trials began in January 2016. There are two treatment rooms, which have same specifications, and the beam quality equivalency was confirmed both rooms. Here, we describe the design and construction of the first hospital-based AB-BNCT facility in the world with multiple treatment rooms.

Characterization of the relationship between neutron production and thermal load on a target material in an accelerator-based boron neutron capture therapy system employing a solid-state Li target.

An accelerator-based boron neutron capture therapy (BNCT) system that employs a solid-state Li target can achieve sufficient neutron flux derived from the 7Li(p,n) reaction. However, neutron production is complicated by the large thermal load expected on the target. The relationship between neutron production and thermal load was examined under various conditions. A target structure for neutron production consists of a Li target and a target basement. Four proton beam profiles were examined to vary the local thermal load on the target structure while maintaining a constant total thermal load. The efficiency of neutron production was evaluated with respect to the total number of protons delivered to the target structure. The target structure was also evaluated by observing its surface after certain numbers of protons were delivered. The yield of the sputtering effect was calculated via a Monte Carlo simulation to investigate whether it caused complications in neutron production. The efficiency of neutron production and the amount of damage done depended on the proton profile. A more focused proton profile resulted in greater damage. The efficiency decreased as the total number of protons delivered to the target structure increased, and the rate of decrease depended on the proton profile. The sputtering effect was not sufficiently large to be a main factor in the reduction in neutron production. The proton beam profile on the target structure was found to be important to the stable operation of the system with a solid-state Li target. The main factor in the rate of reduction in neutron production was found to be the local thermal load induced by proton irradiation of the target.

Development of epi-thermal neutron beam intensity detector with 71Ga(n,γ)72Ga reaction for boron neutron capture therapy.

Based on the activation method using 71Ga(n,γ)72Ga reaction, a cubic neutron flux intensity detector for epi-thermal neutrons was designed for boron neutron capture therapy (BNCT), and experimentally tested with a prototype detector in a neutron field produced at OKTAVIAN facility of Osaka University, Japan. The experimental test results and related analysis indicated that the performance of the detector was confirmed to be acceptable in the neutron field of BNCT. Practically, the neutron flux intensity mainly covering from 0.5 eV to 10 keV can be measured within 3% by the present detector.

Radiation Chemical Yield of Hydroxyl Radicals for Accelerator-based Boron Neutron Capture Therapy: Dose Assessment of 10B(n,α)7Li Reaction Using Coumarin-3-Carboxilic Solution.

Evaluation of the characteristics of accelerator-based thermal neutron fields is recognized as an important issue when discussing the effectiveness of boron neutron capture therapy (BNCT). In this study, we propose that the radiation chemical yield (G value) of hydroxyl radicals (Goh•) can be considered a universal parameter for the description of the accelerator-based thermal neutron field. The Goh• of the 10B(n,α)7Li reaction was quantitatively evaluated using an aqueous coumarin-3-carboxylic acid (3CCA) solution, and was discriminated from that of contaminations (i.e., γ rays and fast neutrons). The Goh• of the 10B(n,α)7Li reaction was 0.107 ± 0.004 OH•/100 eV, which is almost equivalent to that exposed to α particles with an energy of 6.0 MeV. Since the Goh• of γ rays from a 60Co source is 2.03 ± 0.05 OH•/100 eV, this lower value suggests that indirect action by the 10B(n,α)7Li reaction is not dominant in BNCT. However, our results indicate that one can assess the 60Co equivalent dose of the 10B(n,α)7Li reaction in water from the Goh• derived using aqueous 3CCA solution in the accelerator-based thermal neutron field.

Dependence of neutrons generated by 7Li(p,n) reaction on Li thickness under free-air condition in accelerator-based boron neutron capture therapy system employing solid-state Li target.

PURPOSE: An accelerator-based boron neutron capture therapy (BNCT) system with a solid-state Li target is reported to have degradation of the Li target. The degradation reduces the Li thickness, which may change spectra of the generated neutrons corresponding to the Li thickness. This study aims to examine the relationship between the Li thickness and the generated neutrons and to investigate the effects of the Li thickness on the absorbed dose in BNCT. METHOD: The neutron energy spectra were calculated via Monte Carlo simulation for Li thicknesses ranging from 20 to 150 µm. Using the system, the saturated radioactivity of gold induced by reactions between 197Au and the generated neutrons was evaluated with the simulation and the measurement, and those were compared. Additionally, for each Li thickness, the saturated radioactivity was compared with the number of generated neutrons. The absorbed doses delivered by 10B(n,α)7Li, 14N(n,p)14C, 1H(n, g)2H, and (n,n') reactions in water were also calculated for each Li thickness. RESULTS: The measurement and simulation indicated a reduction in the number of neutrons due to the degradation of the Li target. However, the absorbed doses were comparable for each Li thickness when the requisite number of neutrons for BNCT was delivered. Additionally, the saturated radioactivity of 198Au could be a surrogate for the number of neutrons even if the Li thickness was varied. CONCLUSIONS: No notable effect to the absorbed dose was observed when required neutron fluence was delivered in the BNCT even if the degradation of the Li was observed.

Opportunistic dose amplification for proton and carbon ion therapy via capture of internally generated thermal neutrons.

This paper presents Neutron Capture Enhanced Particle Therapy (NCEPT), a method for enhancing the radiation dose delivered to a tumour relative to surrounding healthy tissues during proton and carbon ion therapy by capturing thermal neutrons produced inside the treatment volume during irradiation. NCEPT utilises extant and in-development boron-10 and gadolinium-157-based drugs from the related field of neutron capture therapy. Using Monte Carlo simulations, we demonstrate that a typical proton or carbon ion therapy treatment plan generates an approximately uniform thermal neutron field within the target volume, centred around the beam path. The tissue concentrations of neutron capture agents required to obtain an arbitrary 10% increase in biological effective dose are estimated for realistic treatment plans, and compared to concentrations previously reported in the literature. We conclude that the proposed method is theoretically feasible, and can provide a worthwhile improvement in the dose delivered to the tumour relative to healthy tissue with readily achievable concentrations of neutron capture enhancement drugs.

Radiation safety analysis for the A-BNCT facility in Korea.

A Proton Accelerator based Boron Neutron Capture Therapy (A-BNCT) facility is under development in Korea. Neutron beams for treatment are produced from a beryllium (Be) target and an 8 mA, 10 MeV proton beam. The purpose of the research is a radiation shielding analysis and an activation analysis for the facility design satisfying the radiation safety requirements as well as obtaining an operating license for the radiation facility according to a domestic nuclear commissioning procedure. The radiation shielding analysis was performed using the MCNPX computational particle transport code. The radiation source terms in the facility were evaluated and utilized in the shielding calculations. The minimum concrete thickness satisfying the designated dose rate of 5 µSv/h for the worker's area and 0.25 µSv/h for the public area were estimated and applied to the design. For an assessment of the radiation safety inside the facility, the dose rates were evaluated at several positions, such as behind the shielding door, around the primary barriers near the radiation sources, and in the penetrations of the ducts. The dose rate distribution was mapped for verification of the radiation safety for the entire facility. An activation analysis was carried out for the concrete walls, air, target assembly, beryllium target, and cooling water using FISPACT-2010 code. Concentrations of the activation products and dose rate induced by the radionuclides after shutdown were evaluated for the purpose of safe operation of the facility. The results were reviewed with the radiation safety regulations in Korea. As a result, it was proved that the final facility design satisfies the safety requirements.

Monte Carlo simulation-based design for an electron-linear-accelerator-driven subcritical neutron multiplier for boron neutron capture therapy.

Fuel configurations for a subcritical neutron multiplier, which was embedded in a beam-shaping assembly and irradiated by electrons from a linear accelerator, were examined to maximize the production of the epithermal neutron flux for boron neutron capture therapy. The epithermal neutron flux at the treatment position increased as the area per uranium fuel plate increased and was estimated to be 2 × 109 cm-2 s-1 when the subcritical neutron multiplier was irradiated by a 4.4 kW (0.22 mA) beam of 20 MeV electrons.

Beam shaping assembly design of 7Li(p,n)7Be neutron source for boron neutron capture therapy of deep-seated tumor.

The development of a medical facility for boron neutron capture therapy at Budker Institute of Nuclear Physics is under way. The neutron source is based on a tandem accelerator with vacuum insulation and lithium target. The proposed accelerator is conceived to deliver a proton beam around 10 mA at 2.3 MeV proton beam. To deliver a therapeutic beam for treatment of deep-seated tumors a typical Beam Shaping Assembly (BSA) based on the source specifications has been explored. In this article, an optimized BSA based on the 7Li(p,n)7Be neutron production reaction is proposed. To evaluate the performance of the designed beam in a phantom, the parameters and the dose profiles in tissues due to the irradiation have been considered. In the simulations, we considered a proton energy of 2.3 MeV, a current of 10 mA, and boron concentrations in tumor, healthy tissues and skin of 52.5 ppm, 15 ppm and 22.5 ppm, respectively. It is found that, for a maximum punctual healthy tissue dose seated to 11 RBE-Gy, a mean dose of 56.5 RBE Gy with a minimum of 52.2 RBE Gy can be delivered to a tumor in 40 min, where the therapeutic ratio is estimated to 5.38. All of these calculations were carried out using the Monte Carlo MCNP code.

First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness.

Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy's superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + 11B → 3α reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses 10B-enriched BSH for neutron irradiation-triggered alpha particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy's ballistic precision with the higher RBE promised by BNCT and 12C-ion therapy is thus demonstrated.

DESIGN IMPROVEMENT OF A LIQUID-MODERATOR-BASED NEUTRON SPECTROMETER FOR BNCT.

Boron neutron capture therapy is known to be an effective radiation cancer therapy that requires neutron irradiation. A neutron field generated by an accelerator-based neutron source has various energy spectra, and it is necessary to evaluate the neutron spectrum in the treatment field. However, the method used to measure the neutron spectrum in the treatment field is not well established. Many researchers are making efforts to improve the spectrometers. To solve this problem, we are developing a liquid-moderator-based neutron spectrometer that is based on the same theory as that of the Bonner sphere spectrometer. The spectrometer uses a liquid moderator and absorber. In the present study, we performed a design study to improve the previously developed liquid-moderator-based neutron spectrometer. By carrying out a numerical simulation of the designed new spectrometer, we finally assessed and confirmed the validity of this spectrometer numerically.

High-Dose TL Dosimetry of Reactor Neutrons.

Radiation dose was measured with set of TL dosimeters during checkout of neutron radiation hardness of the ORTEC preamplifier type 142A in the experiment at the MARIA nuclear reactor at the National Centre for Nuclear Research (NCBJ), Otwock-Swierk, Poland. Different types of LiF-based TL detectors have been used for measurements in order to evaluate neutron and non-neutron components of the radiation field in the reactor channel during exposure and to check their relevancy for dose measurements in the reactor environment. For high-dose evaluation a new Ultra-High-Temperature Ratio (UHTR) method established for highly sensitive LiF:Mg,Cu,P detectors has been applied. Neutron fluence evaluated from TL measurements was in good agreement with one calculated using neutron flux data during the experiment.

Physics of epi-thermal boron neutron capture therapy (epi-thermal BNCT).

The physics of epi-thermal neutrons in the human body is discussed in the effort to clarify the nature of the unique radiologic properties of boron neutron capture therapy (BNCT). This discussion leads to the computational method of Monte Carlo simulation in BNCT. The method is discussed through two examples based on model phantoms. The physics is kept at an introductory level in the discussion in this tutorial review.