Boron Neutron Capture Therapy Beam Research Articles

Dose Rate Effect on Cell Survival in BNCT.

The output constancy of the accelerator used for boron neutron capture therapy (BNCT) is essential to ensuring anti-tumor efficacy and safety. BNCT as currently practiced requires a wide variety of beam quality assessments to ensure that RBE dose errors are maintained within 5%. However, the necessity of maintaining a constant beam dose rate has not been fully discussed. We therefore clarified the effect of different physical dose rates of the accelerator BNCT on biological effects. SAS and A172 cells exposed to 10B-boronophenylalanine were irradiated using a neutron beam (normal operating current, 100 μA) at the Aomori Quantum Science Center. Thermal neutron flux was attenuated to 50.0 ± 0.96% under 50 μA irradiation compared to that under 100 μA irradiation. Cells were given physical doses of 1.67 and 3.36 Gy at 30 and 60 mC, respectively, and survival was significantly increased after 50 μA irradiation for both cell types (p = 0.0052 for SAS; p = 0.046 for A172, for 60 mC). Differences in accelerator BNCT beam dose rates have non-negligible effects on biological effects. Dose rate fluctuations and differences should not be easily permitted to obtain consistent biological effects.

BNCT dosimetry for brain cancer based on the nuclear research reactor NUR and the modified MIRD phantom by introducing the eye lens: Simulation study

The Glioblastoma Multiforme (GBM) is one of the most aggressive type of the brain cancer, as well as resistant to treatments combining surgery and concomitant sessions of radiotherapy, based on X-rays, and chemotherapy. The Boron Neutron Capture Therapy (BNCT) has been elected as a radical solution to this type of cancer. This present work focuses on the dosimetric study of the GBM using the therapeutic BNCT beam based on the NUR nuclear research reactor of the Draria Nuclear Research Center (CRND) that has been already optimized in a previous research. In this context, the simulations have been done using the Monte Carlo Code (MCNP5) and the Medical Internal Radiation Dose (MIRD) phantom with an assumption of a brain tumor of 1.5 cm radius situated at different depth ranging from 4 to 10 cm and centered with respect to the neutron beam. In addition, the calculation of the absorbed dose by the tumor, the healthy brain tissue, the skin around head and neck (skin), the pharynx and the thyroid was performed for the different locations of the tumor using the ICRU 46 to determine the elemental composition and the flux to Kerma conversion coefficients for each tissue. However, the recent epidemiological studies show that cataract can occur at a dose lower than 200 cGy, as it can be a stochastic effect and not a deterministic one. To this end, a calculation of the absorbed dose by the lens of the eye and more precisely by its most radiosensitive part (germinative zone) was developed by modifying the MIRD phantom to model the entire eye based on the equations of later studies. The obtained results show that the absorbed dose rate calculated for the tumor increases each time its depth rises, which is not the case for the dose rate calculated for the healthy organs where it remains approximately constant. The absorbed dose by the germinative zone varies from (68.37 ± 0.89) cGy for tumor depth of 4 cm to (733.92 ± 15.96) cGy for a tumor situated at 10 cm of depth.

Readout Electronics for Spatial Distribution Measurement of Neutron Beam Flux in BNCT

Boron neutron capture therapy (BNCT) is a promising cancer treatment that selectively destroys tumor cells using a neutron beam. However, accurately and fast measuring the spatial distribution of neutron flux is critical to ensuring effective treatment. To address this challenge, Micromegas detectors are applied for the first time to measure the spatial distribution of neutron beam flux in BNCT. Due to the high flux, large area, and multiple components of the BNCT beam, the design of readout electronics that can handle high counting rate, large channel numbers, high integration, and discrimination of multiple beam components is challenging. This paper proposes a targeted readout electronics system to overcome this challenge. A modular readout structure based on the PCI Express (PXIe) platform is designed for 384-channel readout. A fully parallel readout structure is developed and fast shaper parameters are optimized to achieve high counting rate for each readout channel. A multi-channel high-speed, large-capacity caching technique is developed to address the high-speed data storage problem. Digital shapers are implemented in field-programmable gate array (FPGA) to achieve high integration. Tests demonstrate that each readout channel can support a counting rate of 800 kHz and achieve an excellent position resolution of 1.4 mm. Furthermore, final tests on the BNCT beam confirm that our system can successfully measure the flux spatial distribution of different neutron components.

A large area, high counting rate micromegas-based neutron detector for BNCT

Beam monitoring and evaluation are very important to boron neutron capture therapy (BNCT), and a variety of detectors have been developed for these applications. However, most of the detectors used in BNCT only have a small detection area, leading to the inconvenience of the full-scale 2-D measurement of the beam. Based on micromegas technology, we designed a neutron detector with large detection area and high counting rate. This detector has a detection area of 288 mm × 288 mm and can measure thermal, epithermal, and fast neutrons with different detector settings. The BNCT experiments demonstrated that this detector has a very good 2-D imaging performance for the thermal, epithermal, fast neutron and gamma components, a highest counting rate of 94 kHz/channel, and a good linearity response to the beam power. Additionally, the flux fraction of each component can be calculated based on the measurement results. The Am-Be neutron source experiment indicates that this detector has a spatial resolution of approximately 1.4 mm, meeting the requirements of applications in BNCT. It is evident that this micromegas-based neutron detector with a large area and high counting rate capability has great development prospects in BNCT beam monitoring and evaluation applications.

Evaluation of RBE-weighted doses for various radiotherapy beams based on a microdosimetric function implemented in PHITS

University of Tsukuba is developing a new TPS for boron neutron capture therapy (BNCT) equipped with Monte Carlo dose-calculation engine based on Particle and Heavy Ion Transport code System PHITS. It is currently in the process of extending its adaptation to other radiotherapy beams. For this extension, not only physical doses but also their relative biological effectiveness (RBE) must be evaluated for various radiotherapy in the same framework. Frequent and dose probability densities of lineal energy, y, are the key quantities in the RBE estimation, and they must be precisely evaluated for various locations in a patient. In this study, the probability densities of y for a site diameter of 0.564 µm were calculated for X-ray, proton, carbon-ion, and BNCT beams with appropriate geometry settings using the microdosimetric function implemented in PHITS, and they were converted to the corresponding RBE-weighted doses using the microdosimetric kinetic model. The accuracy of the calculated data were well verified by several experimental data, indicating the adequacy of the use of PHITS and microdosimetric kinetic model in the dose-calculation engine for TPS applicable to various radiotherapy.

Functionalized mesoporous silica nanoparticles for innovative boron-neutron capture therapy of resistant cancers

Treatment resistance, relapse and metastasis remain critical issues in some challenging cancers, such as chondrosarcomas. Boron-neutron capture therapy (BNCT) is a targeted radiation therapy modality that relies on the ability of boron atoms to capture low energy neutrons, yielding high linear energy transfer alpha particles. We have developed an innovative boron-delivery system for BNCT, composed of multifunctional fluorescent mesoporous silica nanoparticles (B-MSNs), grafted with an activatable cell penetrating peptide (ACPP) for improved penetration in tumors and with gadolinium for magnetic resonance imaging (MRI) in vivo. Chondrosarcoma cells were exposed in vitro to an epithermal neutron beam after B-MSNs administration. BNCT beam exposure successfully induced DNA damage and cell death, including in radio-resistant ALDH+ cancer stem cells (CSCs), suggesting that BNCT using this system might be a suitable treatment modality for chondrosarcoma or other hard-to-treat cancers.

Synthesis and evaluation of thermal neutron attenuation properties of lithium orthosilicate for its application as a beam shaping material on BNCT facilities

Thermal neutron attenuation capacity of Li4SiO4 was evaluated to assess its potential capabilities as a beam shaping material for boron neutron capture therapy (BNCT) facilities. Samples of Li4SiO4 were prepared by two different synthesis methods, using different raw materials and were characterized using x-ray, electron diffraction and transmission electron microscopy. Neutron measurements were performed at the BNCT and the neutron radiography facilities of Centro Atómico Bariloche. Considering its natural isotopic abundance, Li4SiO4 proved to be remarkably effective in comparison with other neutron-absorbing materials. Given the availability of natural Lithium in local salt mines and the scalable feasibility, Li4SiO4 qualifies as a potential material for BNCT beam shaping applications.

Study of dose rate in the brain model based on the neutron beam of SUT-MNSR

Boron neutron capture therapy (BNCT) is tumor-cell targeted radiotherapy that has significant superiority over conventional radiotherapies. The most neutron beams used for BNCT are from the reactors with high power, new design Miniature Neutron Source Reactor(MNSR) with 45kW with BNCT beam for Suranaree University of Technology(SUT) is being designed and built. According to SUT-MNSR physics design, SUT-MNSR will have the epithermal neutron beam for BNCT treatment. The dose rate distribution in the body should be estimated before SUT-MNSR is used for BNCT clinical trials (Brain tumor). This paper introduces the simulation for SUT-MNSR neutron beam by Monte Carlo N-Particle Transport Code (MCNP), and the establishment of human brain model and physics dose rate distribution in brain tumor by MCNP program.The brain model is established according to the different element in the skin, skull and tissue, the distribution of neutron dose and Gamma dose in the brain model were calculated.

In-phantom neutron dose measurement using Gafchromic film dosimeter for QA of BNCT beams

In order to improve the quality assurance (QA) procedure for beams of boron neutron capture therapy (BNCT), this study introduced using the Gafchromic film dosimeter for neutron dose measurement of BNCT beams. The crucial part of this study was investigating an approach to employ the Gafchromic film dosimeter placed inside a PMMA phantom irradiated by a BNCT beam. The spatial distribution of neutron dose of the film was determined using measurements and Monte Carlo calculations. By employing the present approach, the two-dimensional distributions of the neutron dose component of the film at specific depths in the phantom were successfully obtained. The determined neutron dose profiles were in good agreement with the calculated ones. This study also confirmed the finding that the film dosimeter is sensitive to thermal neutrons by comparing the depth-capture-reaction-rate and depth-dose distributions. Results of this work not only proved the feasibility of using the proposed method for the QA measurement of beam delivery but also revealed the advantages of easy-handling and remarkable spatial resolution of the film dosimeter when applied to BNCT fields. The present work can help to verify the dose uniformity and output stability of BNCT beams prior to clinical irradiation.

An optimized epithermal BNCT beam design for research reactors

Boron Neutron Capture Therapy (BNCT) beam design needs a special methodology to satisfy the recommended beam parameters required for the proper delivery of treatment doses. In this work, a new design method for a multi-layered spectrum shifter is proposed in order to improve the design process of epithermal BNCT beams for research reactors. The design method is based on two concepts: stepwise spectrum shifting and separation of the design process into two design stages, namely the material selection and the thickness determination. The method has been applied to two case studies using two different sources: a Watt fission neutron spectrum and neutron-gamma spectra of a typical MTR-type reactor radial beam. The different beam components have been designed with a special focus on the spectrum shifter. Java-based Nuclear Information Software (JANIS) has been used for cross sections computations needed for the selection of the spectrum shifter materials. Monte Carlo N–Particle code “MCNP5” has been used for the beam design. To validate the proposed spectrum shifter design method, comparisons have been done between the proposed spectrum shifter and the known patented material “FLUENTAL™” for both cases. The results of comparisons confirm that the proposed design outperforms the “FLUENTAL™” material. The proposed method proved to be time-saving, simple and efficient. Above all, it is based on a more systematic approach rather than the commonly used approaches. Thus, this method can be applied for other epithermal beams as well as other BNCT facilities such as accelerator-based BNCT facilities.

Geant4 beam model for boron neutron capture therapy: investigation of neutron dose components.

Boron neutron capture therapy (BNCT) is a biochemically-targeted type of radiotherapy, selectively delivering localized dose to tumour cells diffused in normal tissue, while minimizing normal tissue toxicity. BNCT is based on thermal neutron capture by stable [Formula: see text]B nuclei resulting in emission of short-ranged alpha particles and recoil [Formula: see text]Li nuclei. The purpose of the current work was to develop and validate a Monte Carlo BNCT beam model and to investigate contribution of individual dose components resulting of neutron interactions. A neutron beam model was developed in Geant4 and validated against published data. The neutron beam spectrum, obtained from literature for a cyclotron-produced beam, was irradiated to a water phantom with boron concentrations of 100 μg/g. The calculated percentage depth dose curves (PDDs) in the phantom were compared with published data to validate the beam model in terms of total and boron depth dose deposition. Subsequently, two sensitivity studies were conducted to quantify the impact of: (1) neutron beam spectrum, and (2) various boron concentrations on the boron dose component. Good agreement was achieved between the calculated and measured neutron beam PDDs (within 1%). The resulting boron depth dose deposition was also in agreement with measured data. The sensitivity study of several boron concentrations showed that the calculated boron dose gradually converged beyond 100 μg/g boron concentration. This results suggest that 100μg/g tumour boron concentration may be optimal and above this value limited increase in boron dose is expected for a given neutron flux.

Boron neutron capture therapy (BNCT) translational studies in the hamster cheek pouch model of oral cancer at the new "B2" configuration of the RA-6 nuclear reactor.

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.

Investigation of Dose Distribution in Mixed Neutron-Gamma Field of Boron Neutron Capture Therapy using N -Isopropylacrylamide Gel

Gel dosimeters have unique advantages in comparison with other dosimeters. Until now, these gels have been used in different radiotherapy techniques as a reliable dosimetric tool. Because dose distribution measurement is an important factor for appropriate treatment planning in different radiotherapy techniques, in this study, we evaluated the ability of the N-isopropylacrylamide (NIPAM) polymer gel to record the dose distribution resulting from the mixed neutron-gamma field of boron neutron capture therapy (BNCT). In this regard, a head phantom containing NIPAM gel was irradiated using the Tehran Research Reactor BNCT beam line, and then by a magnetic resonance scanner. Eventually, the R-2 maps were obtained in different slices of the phantom by analyzing T2-weighted images. The results show that NIPAM gel has a suitable potential for recording three-dimensional dose distribution in mixed neutron-gamma field dosimetry. Copyright (C) 2016, Published by Elsevier Korea LLC on behalf of Korean Nuclear Society.

Measurement and simulation of the TRR BNCT beam parameters

Recently, the configuration of the Tehran Research Reactor (TRR) thermal column has been modified and a proper thermal neutron beam for preclinical Boron Neutron Capture Therapy (BNCT) has been obtained. In this study, simulations and experimental measurements have been carried out to identify the BNCT beam parameters including the beam uniformity, the distribution of the thermal neutron dose, boron dose, gamma dose in a phantom and also the Therapeutic Gain (TG). To do this, the entire TRR structure including the reactor core, pool, the thermal column and beam tubes have been modeled using MCNPX Monte Carlo code. To measure in-phantom dose distribution a special head phantom has been constructed and foil activation techniques and TLD700 dosimeter have been used. The results show that there is enough uniformity in TRR thermal BNCT beam. TG parameter has the maximum value of 5.7 at the depth of 1cm from the surface of the phantom, confirming that TRR thermal neutron beam has potential for being used in treatment of superficial brain tumors. For the purpose of a clinical trial, more modifications need to be done at the reactor, as, for example design, and construction of a treatment room at the beam exit which is our plan for future. To date, this beam is usable for biological studies and animal trials. There is a relatively good agreement between simulation and measurement especially within a diameter of 10cm which is the dimension of usual BNCT beam ports. This relatively good agreement enables a more precise prediction of the irradiation conditions needed for future experiments.

Measurement of in-phantom neutron flux and gamma dose in Tehran research reactor boron neutron capture therapy beam line.

Determination of in-phantom quality factors of Tehran research reactor (TRR) boron neutron capture therapy (BNCT) beam. The doses from thermal neutron reactions with 14N and 10B are calculated by kinetic energy released per unit mass approach, after measuring thermal neutron flux using neutron activation technique. Gamma dose is measured using TLD-700 dosimeter. Different dose components have been measured in a head phantom which has been designed and constructed for BNCT purpose in TRR. Different in-phantom beam quality factors have also been determined. This study demonstrates that the TRR BNCT beam line has potential for treatment of superficial tumors.

Development of a higher power cooling system for lithium targets

The accelerator based Boron Neutron Capture Therapy beam at the University of Birmingham is based around a solid thick lithium target cooled by heavy water. Significant upgrades to Birmingham's Dynamitron accelerator are planned prior to commencing a clinical trial. These upgrades will result in an increase in maximum achievable beam current to at least 3mA. Various upgrades to the target cooling system to cope with this increased power have been investigated. Tests of a phase change coolant known as “binary ice” have been carried out using an induction heater to provide a comparable power input to the Dynamitron beam. The experimental data shows no improvement over chilled water in the submerged jet system, with both systems exhibiting the same heat input to target temperature relation for a given flow rate. The relationship between the cooling circuit pumping rate and the target temperature in the submerged jet system has also been tested.

Design and construction of a thermal neutron beam for BNCT at Tehran Research Reactor

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 1.2×1.2m2. 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 5.6×108 (ncm−2s−1), a cadmium ratio is 186 for gold foils and a gamma dose rate is 0.57Gyh−1.

Rhodium self‐powered neutron detector as a suitable on‐line thermal neutron flux monitor in BNCT treatments

A rhodium self-powered neutron detector (Rh SPND) has been specifically developed by the Comisión Nacional de Energía Atómica (CNEA) of Argentina to measure locally and in real time thermal neutron fluxes in patients treated with boron neutron capture therapy (BNCT). In this work, the thermal and epithermal neutron response of the Rh SPND was evaluated by studying the detector response to two different reactor spectra. In addition, during clinical trials of the BNCT Project of the CNEA, on-line neutron flux measurements using the specially designed detector were assessed. The first calibration of the detector was done with the well-thermalized neutron spectrum of the CNEA RA-3 reactor thermal column. For this purpose, the reactor spectrum was approximated by a Maxwell-Boltzmann distribution in the thermal energy range. The second calibration was done at different positions along the central axis of a water-filled cylindrical phantom, placed in the mixed thermal-epithermal neutron beam of CNEA RA-6 reactor. In this latter case, the RA-6 neutron spectrum had been well characterized by both calculation and measurement, and it presented some marked differences with the ideal spectrum considered for SPND calibrations at RA-3. In addition, the RA-6 neutron spectrum varied with depth in the water phantom and thus the percentage of the epithermal contribution to the total neutron flux changed at each measurement location. Local (one point-position) and global (several points-positions) and thermal and mixed-field thermal neutron sensitivities were determined from these measurements. Thermal neutron flux was also measured during BNCT clinical trials within the irradiation fields incident on the patients. In order to achieve this, the detector was placed on patient's skin at dosimetric reference points for each one of the fields. System stability was adequate for this kind of measurement. Local mixed-field thermal neutron sensitivities and global thermal and mixed-field thermal neutron sensitivities derived from measurements performed at the RA-6 were compared and no significant differences were found. Global RA-6-based thermal neutron sensitivity showed agreement with pure thermal neutron sensitivity measurements performed in the RA-3 spectrum. Additionally, the detector response proved nearly unchanged by differences in neutron spectra from real (RA-6 BNCT beam) and ideal (considered for calibration calculations at RA-3) neutron source descriptions. The results confirm that the special design of the Rh SPND can be considered as having a pure thermal response for neutron spectra with epithermal-to-thermal flux ratios up to 12%. In addition, the linear response of the detector to thermal flux allows the use of a mixed-field thermal neutron sensitivity of 1.95 ± 0.05 × 10(-21) A n(-1)[middle dot]cm² [middle dot]s. This sensitivity can be used in spectra with up to 21% epithermal-to-thermal flux ratio without significant error due to epithermal neutron and gamma induced effects. The values of the measured fluxes in clinical applications had discrepancies with calculated results that were in the range of -25% to +30%, which shows the importance of a local on-line independent measurement as part of a treatment planning quality control system. The usefulness of the CNEA Rh SPND for the on-line local measurement of thermal neutron flux on BNCT patients has been demonstrated based on an appropriate neutron spectra calibration and clinical applications.

The angular and spatial distributions of the thermal neutron source description of the THOR BNCT beam

This paper presents a way to determine the angular and spatial distributions of the thermal neutron source strength of a boron neutron capture therapy (BNCT) beam. The experiments applied 1) the indirect neutron radiography, 2) the cadmium difference method, and 3) the instrumental neutron activation analysis. The measured data were processed by the spectrum deconvolution technique to resolve into a proper set of angular and spatial distributions. This paper took the epithermal neutron beam of the BNCT facility at the Tsing Hua Open-pool Reactor as an example.

Characterization of a BNCT beam using neutron activation and indirect neutron radiography

This study aims to measure the neutronic characteristics of the 14-cm diameter boron neutron capture therapy beam at the Tsing Hua Open-pool Reactor and to provide essential information for the neutron source adjustment and validation. The measurements were performed both in air and inside a cubic PMMA phantom at the beam, with and without an 18-cm long extended PE collimator. The neutron intensity was determined by neutron activation analysis; the indirect neutron radiography and the cadmium difference method were coupled to provide the two-dimensional neutron flux distributions. According to the measurements, the angular distribution is highly forward for epithermal neutrons but much more divergent for thermal ones. A PE extended collimator will modify the beam characteristics and could benefit the treatment for head and neck tumors, which often needs higher therapeutical boron dose at the shallow region.