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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.

The 7 Li(p,n) 7 Be 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 7 Li(p,n) 7 Be 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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2020. Published by Elsevier Ltd.)

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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.

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

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., Competing Interests: Declaration of competing interest Authors Toshinori Mitsumoto and Satoru Yajima are employees of Sumitomo Heavy Industries, Ltd., Tokyo, Japan., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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.

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., Competing Interests: The authors have declared that no competing interests exist.

Based on the activation method using 71 Ga(n,γ) 72 Ga 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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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 (G oh •) can be considered a universal parameter for the description of the accelerator-based thermal neutron field. The G oh • of the 10 B(n,α) 7 Li 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 G oh • of the 10 B(n,α) 7 Li 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 G oh • of γ rays from a 60 Co source is 2.03 ± 0.05 OH•/100 eV, this lower value suggests that indirect action by the 10 B(n,α) 7 Li reaction is not dominant in BNCT. However, our results indicate that one can assess the 60 Co equivalent dose of the 10 B(n,α) 7 Li reaction in water from the G oh • derived using aqueous 3CCA solution in the accelerator-based thermal neutron field.

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 197 Au 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 10 B(n,α) 7 Li, 14 N(n,p) 14 C, 1 H(n, g) 2 H, 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 198 Au 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., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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.

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 × 10 9 cm -2 s -1 when the subcritical neutron multiplier was irradiated by a 4.4 kW (0.22 mA) beam of 20 MeV electrons., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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 7 Li(p,n) 7 Be 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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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.

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-Świerk, 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.

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) 12 C-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 12 C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p +  11 B → 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 10 B-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 12 C-ion therapy is thus demonstrated.

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.

Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new "B2" configuration. We also evaluated, for the first time in the oral cancer model, the radioprotective effect of histamine against mucositis in precancerous tissue as the dose-limiting tissue. Cancerized pouches were exposed to: BPA-BNCT; BPA-BNCT + histamine; BO: Beam only; BO + histamine; CONTROL: cancerized, no-treatment. BNCT induced severe mucositis, with an incidence that was slightly higher than in "B1" experiments (86 vs 67%, respectively). BO induced low/moderate mucositis. Histamine slightly reduced the incidence of severe mucositis induced by BPA-BNCT (75 vs 86%) and prevented mucositis altogether in BO animals. Tumor overall response was significantly higher in BNCT (94-96%) than in control (16%) and BO groups (9-38%), and did not differ significantly from the "B1" results (91%). Histamine did not compromise BNCT therapeutic efficacy. BNCT radiotoxicity and therapeutic effect at the B1 and B2 configurations of RA-6 were consistent. Histamine slightly reduced mucositis in precancerous tissue even in this overly aggressive oral cancer model, without compromising tumor control.

An electron linear accelerator (Linac) can be used for boron neutron capture therapy (BNCT) by producing thermal neutron flux. In this study, we used a Varian 2300 C/D Linac and MCNPX.2.6.0 code to simulate an electron-photoneutron source for use in BNCT. In order to decelerate the produced fast neutrons from the photoneutron source, which optimize the thermal neutron flux, a beam-shaping assembly (BSA) was simulated. After simulations, a thermal neutron flux with sharp peak at the beam exit was obtained in the order of 3.09×10 8 n/cm 2 s and 6.19×10 8 n/cm 2 s for uranium and enriched uranium (10%) as electron-photoneutron sources respectively. Also, in-phantom dose analysis indicates that the simulated thermal neutron beam can be used for treatment of shallow skin melanoma in time of about 85.4 and 43.6min for uranium and enriched uranium (10%) respectively., (Copyright © 2016. Published by Elsevier Ltd.)

Rheumatoid arthritis is a chronic autoimmune pathology characterized by the proliferation and inflammation of the synovium. Boron neutron capture synovectomy (BNCS), a binary treatment modality that combines the preferential incorporation of boron carriers to target tissue and neutron irradiation, was proposed to treat the pathological synovium in arthritis. In a previous biodistribution study, we showed the incorporation of therapeutically useful boron concentrations to the pathological synovium in a model of antigen-induced arthritis (AIA) in rabbits, employing two boron compounds approved for their use in humans, i.e., decahydrodecaborate (GB-10) and boronophenylalanine (BPA). The aim of the present study was to perform low-dose BNCS studies at the RA-1 Nuclear Reactor in the same model. Neutron irradiation was performed post intra-articular administration of BPA or GB-10 to deliver 2.4 or 3.9 Gy, respectively, to synovium (BNCS-AIA). AIA and healthy animals (no AIA) were used as controls. The animals were followed clinically for 2 months. At that time, biochemical, magnetic resonance imaging (MRI) and histological studies were performed. BNCS-AIA animals did not show any toxic effects, swelling or pain on palpation. In BNCS-AIA, the post-treatment levels of TNF-α decreased in four of six rabbits and IFN-γ levels decreased in five of six rabbits. In all cases, MRI images of the knee joint in BNCS-AIA resembled those of no AIA, with no necrosis or periarticular effusion. Synovial membranes of BNCS-AIA were histologically similar to no AIA. BPA-BNCS and GB-10-BNCS, even at low doses, would be therapeutically useful for the local treatment of rheumatoid arthritis.

The neutron beam monitoring system is indispensable to BNCT facility in order to achieve an accurate patient dose delivery. The neutron beam monitoring of a reactor-based BNCT (RB-BNCT) facility can be implemented through the instrumentation and control system of a reactor provided that the reactor power level remains constant during reactor operation. However, since the neutron flux in reactor core is highly correlative to complicated reactor kinetics resulting from such as fuel depletion, poison production, and control blade movement, some extent of variation may occur in the spatial distribution of neutron flux in reactor core. Therefore, a dedicated neutron beam monitoring system is needed to be installed in the vicinity of the beam path close to the beam exit of the RB-BNCT facility, where it can measure the BNCT beam intensity as closely as possible and be free from the influence of the objects present around the beam exit. In this study, in order to demonstrate the importance of a dedicated BNCT neutron beam monitoring system, the signals originating from the two in-core neutron detectors installed at THOR were extracted and compared with the three dedicated neutron beam monitors of the THOR BNCT facility. The correlation of the readings between the in-core neutron detectors and the BNCT neutron beam monitors was established to evaluate the improvable quality of the beam intensity measurement inferred by the in-core neutron detectors. In 29 sampled intervals within 16 days of measurement, the fluctuations in the mean value of the normalized ratios between readings of the three BNCT neutron beam monitors lay within 0.2%. However, the normalized ratios of readings of the two in-core neutron detectors to one of the BNCT neutron beam monitors show great fluctuations of 5.9% and 17.5%, respectively., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Filtered neutron techniques were applied to produce quasi-mono-energetic neutron beams in the energy range of 1.5-7.5 keV at the accelerator port using the generated neutron spectrum from a Li (p, n) Be reaction. A simulation study was performed to characterize the filter components and transmitted beam lines. The feature of the filtered beams is detailed in terms of optimal thickness of the primary and additive components. A computer code named "QMNB-AS" was developed to carry out the required calculations. The filtered neutron beams had high purity and intensity with low contamination from the accompanying thermal, fast neutrons and γ-rays., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The beam-shaping assembly for boron neutron capture therapies with a compact accelerator-driven subcritical neutron multiplier was designed so that an epithermal neutron flux of 1.9×10(9) cm(-2) s(-1) at the treatment position was generated by 5 MeV protons in a beam current of 2 mA. Changes in the atomic density of (135)Xe in the nuclear fuel due to the operation of the beam-shaping assembly were estimated. The criticality safety of the beam-shaping assembly in terms of Xe poisoning is discussed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We evaluated the accelerator beam power and the neutron-induced radioactivity of (9)Be(p, n) boron neutron capture therapy (BNCT) neutron sources having a MgF2, CaF2, or AlF3 moderator and driven by protons with energy from 8 MeV to 30 MeV. The optimal moderator materials were found to be MgF2 for proton energies less than 10 MeV because of lower required accelerator beam power and CaF2 for higher proton energies because of lower photon dose rate at the treatment position after neutron irradiation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Quality assurance of the spatial distributions of neutrons and gamma rays was tried using imaging plates (IPs) and converters to enhance the beam components in the epithermal neutron mode of the Kyoto University Reactor. The converters used were 4mm thick epoxy resin with B4C at 6.85 weight-percent (wt%) (10)B for epithermal neutrons, and 3mm thick carbon for gamma rays. Results suggested that the IP signal does not need a sensitivity correction regardless of the incident radiation that produces it., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In this work, a novel sensor technology based on CdTe detectors was tested for prompt gamma and neutron detection using boronated targets in (epi)thermal neutron beam at FiR1 research reactor in Espoo, Finland. Dedicated neutron filter structures were omitted to enable simultaneous measurement of both gamma and neutron radiation at low reactor power (2.5 kW). Spectra were collected and analyzed in four different setups in order to study the feasibility of the detector to measure 478 keV prompt gamma photons released from the neutron capture reaction of boron-10. The detector proved to have the required sensitivity to detect and separate the signals from both boron neutron and cadmium neutron capture reactions, which makes it a promising candidate for monitoring the spatial and temporal development of in vivo boron distribution in boron neutron capture therapy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A prompt gamma neutron activation analysis (PGNAA) system has been recently developed at the 30-kW research reactor In-Hospital Neutron Irradiator (IHNI) in Beijing. Neutrons from the specially designed thermal neutron beam were used. The thermal flux of this beam is 3.08×10(6) cm(-2) s(-1) at a full reactor power of 30 kW. The PGNAA system consists of an n-type high-purity germanium (HPGe) detector of 40% efficiency, a digital spectrometer, and a shielding part. For both the detector shielding part and the neutron beam shielding part, the inner layer is composed of (6)Li2CO3 powder and the outer layer lead. The boron-10 sensitivity of the PGNAA system is approximately 2.5 cps/ppm. Two calibration curves were produced for the 1-10 ppm and 10-50 ppm samples. The measurement results of the control samples were in accordance with the inductively coupled plasma atomic emission spectroscopy (ICP-AES) results., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In this work we provide some information on the present status of accelerator-based BNCT (AB-BNCT) worldwide and subsequently concentrate on the recent accelerator technology developments in Argentina., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The capability of N-isopropylacrylamide (NIPAM) polymer gel to record the dose resulting from boron neutron capture reaction in BNCT was determined. In this regard, three compositions of the gel with different concentrations of (10)B were prepared and exposed to gamma radiation and thermal neutrons. Unlike irradiation with gamma rays, the boron-loaded gels irradiated by neutron exhibited sensitivity enhancement compared with the gels without (10)B. It was also found that the neutron sensitivity of the gel increased by the increase of concentration of (10)B. It can be concluded that NIPAM gel might be suitable for the measurement of the absorbed dose enhancement due to (10)B and thermal neutron reaction in BNCT., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: Research and development of various accelerator-based irradiation systems for boron neutron capture therapy (BNCT) is underway throughout the world. Many of these systems are nearing or have started clinical trials. Before the start of treatment with BNCT, the relative biological effectiveness (RBE) for the fast neutrons (over 10 keV) incident to the irradiation field must be estimated. Measurements of RBE are typically performed by biological experiments with a phantom. Although the dose deposition due to secondary gamma rays is dominant, the relative contributions of thermal neutrons (below 0.5 eV) and fast neutrons are virtually equivalent under typical irradiation conditions in a water and/or acrylic phantom. Uniform contributions to the dose deposited from thermal and fast neutrons are based in part on relatively inaccurate dose information for fast neutrons. This study sought to improve the accuracy in the dose estimation for fast neutrons by using two phantoms made of different materials in which the dose components can be separated according to differences in the interaction cross sections. The development of a "dual phantom technique" for measuring the fast neutron component of dose is reported., Methods: One phantom was filled with pure water. The other phantom was filled with a water solution of lithium hydroxide (LiOH) capitalizing on the absorbing characteristics of lithium-6 (Li-6) for thermal neutrons. Monte Carlo simulations were used to determine the ideal mixing ratio of Li-6 in LiOH solution. Changes in the depth dose distributions for each respective dose component along the central beam axis were used to assess the LiOH concentration at the 0, 0.001, 0.01, 0.1, 1, and 10 wt. % levels. Simulations were also performed with the phantom filled with 10 wt. % 6LiOH solution for 95%-enriched Li-6. A phantom was constructed containing 10 wt. % 6LiOH solution based on the simulation results. Experimental characterization of the depth dose distributions of the neutron and gamma-ray components along the central axis was performed at Heavy Water Neutron Irradiation Facility installed at Kyoto University Reactor using activation foils and thermoluminescent dosimeters, respectively., Results: Simulation results demonstrated that the absorbing effect for thermal neutrons occurred when the LiOH concentration was over 1%. The most effective Li-6 concentration was determined to be enriched 6LiOH with a solubility approaching its upper limit. Experiments confirmed that the thermal neutron flux and secondary gamma-ray dose rate decreased substantially; however, the fast neutron flux and primary gamma-ray dose rate were hardly affected in the 10%-6LiOH phantom. It was confirmed that the dose contribution of fast neutrons is improved from approximately 10% in the pure water phantom to approximately 50% in the 10%-6LiOH phantom., Conclusions: The dual phantom technique using the combination of a pure water phantom and a 10%-6LiOH phantom developed in this work provides an effective method for dose estimation of the fast neutron component in BNCT. Improvement in the accuracy achieved with the proposed technique results in improved RBE estimation for biological experiments and clinical practice.

Boron neutron capture therapy (BNCT) that is of the highest attractiveness due to its selective action directly on malignant tumor cells is a promising approach to treating cancers. Clinical interest in BNCT focuses in neuro-oncology on therapy for gliomas, glioblastoma in particular, and BNCT may be used in brain metastatic involvement. This needs an epithermal neutron source that complies with the requirements for BNCT, as well as a 10B-containing agent that will selectively accumulate in tumor tissue. The introduction of BNCT into clinical practice to treat patients with glial tumors will be able to enhance therapeutic efficiency.

A feasibility study was performed to design thermal and epithermal neutron sources for radioisotope production and boron neutron capture therapy (BNCT) by moderating fast neutrons. The neutrons were emitted from the reaction between (9)Be, (181)Ta, and (184)W targets and 30 MeV protons accelerated by a small cyclotron at 300 μA. In this study, the adiabatic resonance crossing (ARC) method was investigated by means of (207)Pb and (208)Pb moderators, graphite reflector, and boron absorber around the moderator region. Thermal/epithermal flux, energy, and cross section of accumulated neutrons in the activator were examined through diverse thicknesses of the specified regions. Simulation results revealed that the (181)Ta target had the highest neutron yield, and also tungsten was found to have the highest values in both surface and volumetric flux ratio. Transmutation in the (98)Mo sample through radiative capture was investigated for the natural lead moderator. When the sample radial distance from the target was increased inside the graphite region, the production yield had the greatest value of activity. The potential of the ARC method is a replacement or complements the current reactor-based supply sources of BNCT purposes.

Bonner sphere is useful to evaluate the neutron spectrum in detail. We are improving the energy resolution in epi-thermal neutron region of Bonner sphere, using boric acid water solution as a moderator. Its response function peak is narrower than that for polyethylene moderator and the improvement of the resolution is expected. The resolutions between polyethylene moderator and boric acid water solution moderator were compared by simulation calculation. Also the influence in the uncertainty of Bonner sphere configuration to spectrum estimation was simulated., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Gel dosimeters have acquired a unique status in radiotherapy, especially with the advent of the new techniques in which there is a need for three-dimensional dose measurement with high spatial resolution. One of the techniques in which the use of gel dosimeters has drawn the attention of the researchers is the boron neutron capture therapy. Exploring the history of gel dosimeters, this paper sets out to study their role in the boron neutron capture therapy dosimetric process., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA-3 reactor in the province of Buenos Aires, Argentina. (l)-4p-dihydroxy-borylphenylalanine fructose complex (BPA-F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT., Methods: Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA-3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario., Results: Concentration-time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung-to-blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA-F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 ± 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor-to-normal boron concentration ratio of 2., Conclusions: This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life.

This paper aims to describe the modification of the radial beam port of ITU (İstanbul Technical University) TRIGA Mark II research reactor for BNCT applications. Radial beam port is modified with Polyethylene and Cerrobend collimators. Neutron flux values are measured by neutron activation analysis (Au-Cd foils). Experimental results are verified with Monte Carlo results. The results of neutron/photon spectrum, thermal/epithermal neutron flux, fast group photon fluence and change of the neutron fluxes with the beam port length are presented., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Phantom experiments to evaluate thermal neutron flux distribution were performed using the Scintillator with Optical Fiber (SOF) detector, which was developed as a thermal neutron monitor during boron neutron capture therapy (BNCT) irradiation. Compared with the gold wire activation method and Monte Carlo N-particle (MCNP) calculations, it was confirmed that the SOF detector is capable of measuring thermal neutron flux as low as 10(5) n/cm(2)/s with sufficient accuracy. The SOF detector will be useful for phantom experiments with BNCT neutron fields from low-current accelerator-based neutron sources., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

External carcinogens, such as tobacco and alcohol, induce molecular changes in large areas of oral mucosa, which increase the risk of malignant transformation. This condition, known as 'field cancerization', can be detected in biopsy specimens using histochemical techniques, even before histological alterations are identified. The efficacy of these histochemical techniques as biomarkers of early cancerization must be demonstrated in appropriate models. The hamster cheek pouch oral cancer model, universally employed in biological studies and in studies for the prevention and treatment of oral cancer, is also an excellent model of field cancerization. The carcinogen is applied in solution to the surface of the mucosa and induces alterations that recapitulate the stages of cancerization in human oral mucosa. We have demonstrated that the following can be used for the early detection of cancerized tissue: silver staining of nucleolar organizer regions; the Feulgen reaction to stain DNA followed by ploidy analysis; immunohistochemical analysis of fibroblast growth factor-2, immunohistochemical labeling of proliferating cells to demonstrate an increase of epithelial cell proliferation in the absence of inflammation; and changes in markers of angiogenesis (i.e. those indicating vascular endothelial growth factor activity, endothelial cell proliferation and vascular density). The hamster cheek pouch model of oral cancer was also proposed and validated by our group for boron neutron capture therapy studies for the treatment of oral cancer. Clinical trials of this novel treatment modality have been performed and are underway for certain tumor types and localizations. Having demonstrated the efficacy of boron neutron capture therapy to control tumors in the hamster cheek pouch oral cancer model, we adapted the model for the long-term study of field cancerized tissue. We demonstrated the inhibitory effect of boron neutron capture therapy on tumor development in field cancerized tissue with acceptable levels of mucositis, a dose-limiting side-effect., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed., Methods: Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particle spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a (60)Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes fluka and mcnp. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen & Olsen alanine response model., Results: The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields., Conclusions: The alanine detector can be used without difficulty in neutron fields. The response has been understood with the model used which includes the relative effectiveness. Results and the corresponding discussion lead to the conclusion that application in neutron fields for medical purpose is limited by its sensitivity but that it is a useful tool as supplement to other detectors and verification of neutron source descriptions.

An irradiation facility has been designed and constructed at Tehran Research Reactor (TRR) for the treatment of shallow tumors using Boron Neutron Capture Therapy (BNCT). TRR has a thermal column which is about 3m in length with a wide square cross section of 1.2×1.2m(2). This facility is filled with removable graphite blocks. The aim of this work is to perform the necessary modifications in the thermal column structure to meet thermal BNCT beam criteria recommended by International Atomic Energy Agency. The main modifications consist of rearranging graphite blocks and reducing the gamma dose rate at the beam exit. Activation foils and TLD700 dosimeter have been used to measure in-air characteristics of the neutron beam. According to the measurements, a thermal flux is 5.6×10(8) (ncm(-2)s(-1)), a cadmium ratio is 186 for gold foils and a gamma dose rate is 0.57Gy h(-1)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Boron-neutron capture therapy (BNCT) is an attractive technique for cancer treatment. As such, α, α-cycloalkyl amino acids containing thiododecaborate ([B12H11](2-)-S-) units were designed and synthesized as novel boron delivery agents for BNCT. In the present study, new thiododecaborate α, α-cycloalkyl amino acids were synthesized, and biological evaluation of the boron compounds as boron carrier for BNCT was carried out.

Purpose: In order to build up a reliable dose monitoring system for boron neutron capture therapy (BNCT) applications at the TRIGA reactor in Mainz, a computer model for the entire reactor was established, simulating the radiation field by means of the Monte Carlo method. The impact of different source definition techniques was compared and the model was validated by experimental fluence and dose determinations., Methods: The depletion calculation code origen2 was used to compute the burn-up and relevant material composition of each burned fuel element from the day of first reactor operation to its current core. The material composition of the current core was used in a mcnp5 model of the initial core developed earlier. To perform calculations for the region outside the reactor core, the model was expanded to include the thermal column and compared with the previously established attila model. Subsequently, the computational model is simplified in order to reduce the calculation time. Both simulation models are validated by experiments with different setups using alanine dosimetry and gold activation measurements with two different types of phantoms., Results: The mcnp5 simulated neutron spectrum and source strength are found to be in good agreement with the previous attila model whereas the photon production is much lower. Both mcnp5 simulation models predict all experimental dose values with an accuracy of about 5%. The simulations reveal that a Teflon environment favorably reduces the gamma dose component as compared to a polymethyl methacrylate phantom., Conclusions: A computer model for BNCT dosimetry was established, allowing the prediction of dosimetric quantities without further calibration and within a reasonable computation time for clinical applications. The good agreement between the mcnp5 simulations and experiments demonstrates that the attila model overestimates the gamma dose contribution. The detailed model can be used for the planning of structural modifications in the thermal column irradiation channel or the use of different irradiation sites than the thermal column, e.g., the beam tubes.

Monte Carlo simulations were performed to evaluate dose for possible treatment of cancers by boron neutron capture therapy (BNCT). The computational model of male Oak Ridge National Laboratory (ORNL) phantom was used to simulate tumours in the lung. Calculations have been performed by means of the MCNP5/X code. In this simulation, two opposite neutron beams were considered, in order to obtain uniform neutron flux distribution inside the lung. The obtained results indicate that the lung cancer could be treated by BNCT under the assumptions of calculations., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Central Laboratory for Radiological Protection is involved in achieving scientific project on biological dosimetry. The project includes irradiation of blood samples in radiation fields of nuclear reactor. A simple facility for irradiation of biological samples has been prepared at horizontal channel of the nuclear reactor MARIA in NCBJ in Poland. The radiation field, composed mainly of gamma radiation and thermal neutrons, has been characterised in terms of tissue kerma using twin-detector technique and recombination chambers., (© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The (7)Li(p,xn)(7)Be nuclear reaction, based on the low-energy protons, could produce soft neutrons for accelerator-based boron neutron capture therapy (AB-BNCT). Based on the fact that the induced neutron field is relatively divergent, the relationship between the incident angle of proton beam and the neutron beam quality was evaluated in this study. To provide an intense epithermal neutron beam, a beam-shaping assembly (BSA) was designed. And a modified Snyder head phantom was used in the calculations for evaluating the dosimetric performance. From the calculated results, the intensity of epithermal neutrons increased with the increase in proton incident angle. Hence, either the irradiation time or the required proton current can be reduced. When the incident angle of 2.5-MeV proton beam is 120°, the required proton current is ∼13.3 mA for an irradiation time of half an hour., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Investigation on the use of the Tehran Research Reactor (TRR) as a neutron source for Boron Neutron Capture Therapy (BNCT) has been performed by calculating and measuring energy spectrum and the spatial distribution of neutrons in all external irradiation facilities, including six beam tubes, thermal column, and the medical room. Activation methods with multiple foils and a copper wire have been used for the mentioned measurements. The results show that (1) the small diameter and long length beam tubes cannot provide sufficient neutron flux for BNCT; (2) in order to use the medical room, the TRR core should be placed in the open pool position, in this situation the distance between the core and patient position is about 400 cm, so neutron flux cannot be sufficient for BNCT; and (3) the best facility which can be adapted for BNCT application is the thermal column, if all graphite blocks can be removed. The epithermal and fast neutron flux at the beginning of this empty column are 4.12×10(9) and 1.21×10(9) n/cm(2)/s, respectively, which can provide an appropriate neutron beam for BNCT by designing and constructing a proper Beam Shaping Assembly (BSA) structure., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A target cooling system was developed for an intense neutron source of p-Li reaction. The system consists of target cooling devices and protection devices for lithium evaporation. A pin-structure cooling device was developed to enhance cooling power. Functional graded material was utilized for the evaporation of lithium. Test experiments were performed by using the neutron exposure accelerator system for biological effect experiments (NASBEE) at the National Institute of Radiological Sciences (NIRS) in Japan. The target system was confirmed to be applicable for accelerator-based boron neutron capture therapy., (Copyright © 2014 Elsevier Ltd. All rights reserved.)