Neutron Source For Boron Neutron Capture Therapy Research Articles

Neutron Activation Analysis Based on AB-BNCT Treatment Room.

Boron neutron capture therapy (BNCT) is an ideal binary targeted radiotherapy for treating refractory tumors. An accelerator-based BNCT (AB-BNCT) neutron source has attracted more and more attention due to its advantages such as higher neutron yield in the keV energy region, less gamma radiation, and higher safety. In addition to 10B, neutrons also react with other elements in the treatment room during BNCT to produce many activation products. Due to the long half-life of some activation products, there will be residual radiation after the end of treatment and the shutdown of the accelerator, which has adverse effects on radiation workers. Therefore, the ambient dose equivalent rate in the treatment room needs to be evaluated. The AB-BNCT neutron source model proposed by Li is studied in this paper. Based on the Monte Carlo method, the Geant4 platform was used to simulate the dose induced by radionuclides near the Beam Shaping Assembly (BSA) of the source. It is concluded that the concrete wall contributed the most to the radiation dose. The dose rate of 2.45 μSv h-1 after 13 min of shutdown meets the dose rate limit of 2.5 μSv h-1, at which point it is safe for workers to enter the treatment room area.

Conceptional design of an adjustable moderator for BNCT based on a neutron source of 2.8 MeV proton bombarding with Li target

Beam shaping assembly (BSA) is a vital component in Boron Neutron Capture Therapy (BNCT) for obtaining epithermal neutron beams. Several feasible designs of BSA for accelerator-based BNCT (AB-BNCT) neutron source are carried out based on neutrons by bombarding a natural lithium target with 10 mA, 2.8 MeV proton beams. The calculation results demonstrate that a thickness of 45 cm is appropriate for general moderators referring to the therapeutic parameter of Advanced Depth (AD). A series of optimizations are performed and two results are confirmed: One is that employing the configuration of MgF2 and FLUENTAL combined by 1:1 could improve the therapeutic rate (TR) of tumors at a depth of middle region, and the other one is that the TR of superficial tumors can be increased by adding a 5 cm thick boron-11 secondary moderator at the end of general moderators. As a result, an innovative conception of an adjustable moderator is recommended to BNCT. Compared to the MgF2 moderator with a fixed thickness of 45 cm, the TR value can be improved by a maximum of 47.7 % by using the adjustable moderator. Furthermore, the configuration of adjustable moderator has been designed with regulation method for treating tumors of different depths.

Current development status of accelerator-based neutron source for boron neutron capture therapy

Recently, progress in technology for accelerator-based neutron sources has increased attention regarding boron neutron capture therapy (BNCT). BNCT is a type of radiotherapy that combines neutrons and boron drugs and is expected to be used in the treatment of refractory and recurrent cancers. Owing to the need for high-intensity neutrons in treatment, compact accelerator-based neutron sources applicable to BNCT are being developed worldwide. These current projects utilize cyclotrons, linear accelerators, and electrostatic accelerators as accelerators for BNCT devices. Beryllium and lithium are the main target materials for neutron generation. The accelerators for BNCT device are required to accelerate charged particles with an average current ranging from a few milliamperes to a few tens of milliamperes in order to generate neutrons of sufficient intensity for the treatment. Moreover, the target systems require technologies and mechanisms that can withstand the large heat load produced by high-power beam irradiation and prevent blistering. This review outlines and explains the accelerator neutron sources for BNCT and the requirements for the components of each device, such as the accelerator, target material, and beam shaping assembly. In addition, various development projects for accelerator-based BNCT devices worldwide are introduced.

Experimentally determined relative biological effectiveness of cyclotron-based epithermal neutrons designed for clinical BNCT: in vitro study.

A neutron beam for boron neutron capture therapy (BNCT) of deep-seated tumours is designed to maintain a high flux of epithermal neutrons, while keeping the thermal and fast neutron component as low as possible. These neutrons (thermal and fast) have a high relative biological effectiveness in comparison with high energy photon beams used for conventional X-ray radiotherapy. In the past, neutrons for the purpose of BNCT were generated using nuclear reactors. However, there are various challenges that arise when installing a reactor in a hospital environment. From 2006, the Kyoto University Research Reactor Institute, in collaboration with Sumitomo Heavy Industries, began the development of an accelerator-based neutron source for clinical BNCT in a bid to overcome the shortcomings of a nuclear reactor-based neutron source. Following installation and beam performance testing, in vitro studies were performed to assess the biological effect of the neutron beam. Four different cell lines were prepared and irradiated using the accelerator-based neutron source. Following neutron and gamma ray irradiation, the survival curve for each cell line was calculated. The biological end point to determine the relative biological effectiveness (RBE) was set to 10% cell survival, and the D10 for each cell line was determined. The RBE of the accelerator-based neutron beam was evaluated to be 2.62.

Current development status of iBNCT001, demonstrator of a LINAC-based neutron source for BNCT

The iBNCT project aims to develop “iBNCT001,” a demonstration device of the linac-based neutron irradiation facility for boron neutron capture therapy (BNCT) application. iBNCT001 generates an epithermal neutron beam by irradiating 8 MeV protons accelerated by a linac onto a beryllium target. Currently, the linac can drive an average proton current of 2.1 mA. Several experiments were performed using a water phantom to confirm the main physical characteristics of the neutron beam produced at the irradiation position. The measurement results demonstrated that the maximum thermal neutron flux achievable in the phantom volume was approximately 1.36 × 10 9 cm − 2 s − 1 when a normal beam collimator with a 120 mm diameter was used. This neutron beam intensity was sufficient to complete the irradiation within 30 min using the BNCT approach. In addition to normal beam collimators, extended collimators that protrude 100 mm from the wall were developed. By using an extended collimator, it is possible to prevent interference of the patient’s body with the wall when irradiating head and neck cancers. The measurement results for the extended collimator demonstrated that irradiation with the collimator could be completed within 1 h when the neutron beam is generated with an average proton current of 2.1 mA.

Development of a Clinical Neutron Source for Boron Neutron Capture Therapy

<h3>Purpose/Objective(s)</h3> In boron neutron capture therapy (BNCT), a source of epithermal (1 eV to 30 keV) neutrons activates high concentrations of ¹⁰B, selectively accumulated in tumor cells from infusion of a non-radioactive pharmaceutical, whose high LET reaction products fully deposit their energy within 10 microns of the reaction site. Historically, only nuclear reactors provided sufficient neutron intensity and beam quality for clinically acceptable BNCT treatments, but hospital-based BNCT is now feasible using compact accelerator sources. The present work has designed a system to produce an epithermal neutron beam using a tandem electrostatic accelerator, proton beam line, neutron-producing targets, neutron beam shaping assembly (BSA) and collimators. Testing was required to verify that this design can produce a clinically viable neutron source for BNCT in terms of total neutron yield, output reproducibility and operational stability. <h3>Materials/Methods</h3> The present neutron source uses neutrons from the ⁷Li(p,n)⁷Be reaction at nominal proton energy and current of 2.5 MeV and 10 mA. A negative hydrogen ion source is pre-accelerated to 200 keV and injected into the tandem accelerator, which increases the negative ion kinetic energy to half the goal proton energy at its center. A charge exchange target strips the electrons to create positively-charged protons that are further accelerated to the full operational energy at the tandem exit. The proton beam is focused and may be directed to up to three treatment rooms, each with a copper-backed target of natural lithium metal under vacuum. The maximum neutron energy from 2.5 MeV protons slowing down in lithium is 800 keV and requires moderation to the desired epithermal range. A static beam BSA surrounds the target and provides efficient neutron moderation and reflection using carefully chosen materials. The BSA's 25 cm circular exit port may be collimated to small circular epithermal beam diameters as small as 5-8 cm. <h3>Results</h3> A tandem accelerator, proton beam line and lithium target have been installed and began initial testing. Proton energy and current up to 2.3 MeV and 7 mA have been achieved for continuous operating periods exceeding 30 minutes with no energy or current degradation. Raster patterns have been designed to scan the 1-cm diameter proton beam over a 10-cm circular area on the lithium target, and water cooling of the copper backing has maintained maximum target temperatures below 150°C. The measured lithium deposition uniformity is expected to translate to a neutron yield uniformity better than 5%. <h3>Conclusion</h3> This BNCT neutron source has demonstrated operational stability and reproducibility of proton energy, proton current and neutron production. These measurements support an expectation that the equipment currently undergoing evaluation, in combination with the planned BSA, will meet the necessary requirements for a hospital-based, clinical BNCT system.

From Nuclear Reactor-Based to Proton Accelerator-Based Therapy: The Finnish Boron Neutron Capture Therapy Experience.

The authors review the results of 249 patients treated with boron neutron capture therapy (BNCT) at the Helsinki University Hospital, Helsinki, Finland, from May 1999 to January 2012 with neutrons obtained from a nuclear reactor source (FiR 1) and using l-boronophenylalanine-fructose (l-BPA-F) as the boron delivery agent. They also describe a new hospital BNCT facility that hosts a proton accelerator-based neutron source for BNCT. Most of the patients treated with nuclear reactor-derived neutrons had either inoperable, locally recurrent head and neck cancer or malignant glioma. In general, l-BPA-F-mediated BNCT was relatively well tolerated with adverse events usually similar to those of conventional radiotherapy. Twenty-eight (96.6%) out of the evaluable 29 patients with head and neck cancer and treated within a clinical trial either responded to BNCT or had tumor growth stabilization for at least 5 months, suggesting efficacy of BNCT in the treatment of this patient population. The new accelerator-based BNCT facility houses a nuBeam neutron source that consists of an electrostatic Cockcroft-Walton-type proton accelerator and a lithium target that converts the proton beam to neutrons. The proton beam energy is 2.6 MeV operating with a current of 30 mA. Treatment planning is based on Monte Carlo simulation and the RayStation treatment planning system. Patient positioning is performed with a 6-axis robotic image-guided system, and in-room imaging is done with a rail-mounted computed tomography scanner. Under normal circumstances, the personnel can enter the treatment room almost immediately after shutting down the proton beam, which improves the unit capacity. ClinicalTrials.gov ID: NCT00114790.

Status and outlook: Research and development on the neutron source for BNCT

<p indent=0mm>Boron neutron capture therapy (BNCT) is regarded as a revolutionary means for high-accuracy cancer therapy with cell level selectivity. It has unique therapeutic effects for some malignance, such as glioblastoma multiforme, melanoma, recurrent head and neck malignance. It can also be used for cancer treatment of deep organ, such as liver and lung. Even though its principle was proposed about <sc>80 years</sc> ago, it has never been utilized in routine clinic therapy in hospital until 2020. BNCT, as a binary therapeutic method, greatly depends on both high-quality neutron beam and highly target-selective boron drug. Tumor killing in cell-level accuracy can be achieved only when the two elements work together and collaborate closely. To realize such therapeutic effect, BNCT sets high requirement on both neutron source and boron drug. The research on boron drug is related with multi-disciplines, such as chemistry, biology, medicine, radiology, pharmacy and physics. This article focuses on the neutron source for BNCT. Commonly, there are two types of BNCT neutron sources: reactor-based neutron source and accelerator-based neutron source. Up to now, almost all clinic trails of BNCT therapy were performed with the former. Due to limited resources of reactor neutron source, only less than 2000 cases BNCT treatments have been carried out in the world since BNCT method was invented. Thanks for the intense beam proton accelerator development, accelerator based neutron source can provide better beam quality, and especially importantly it can be installed in a hospital environment, which is essential for wide-range application of BNCT. In accelerator-based BNCT field, China has a sound base owing to more than <sc>20 years</sc> research and development in high intensity neutron source for spallation neutron source and accelerator-driven subcritical system. It is meaningful work to transfer the related technology to accelerator-based BNCT (AB-BNCT). In this paper we will firstly introduce the demand on neutron beam specification recommended by IAEA. Then the difficulties in BNCT slow development in passing decades are reviewed. New era of BNCT is coming and one can expect a prosperous future, owing to accelerator-based BNCT. The core technology of AB-BNCT is explored and recent research achievements on BNCT research and development in China are reported. Various types of accelerators now can be used for BNCT facility, including electro-static high voltage, cyclotron and RF linac. Their pro and con are reviewed. Majorly two kinds of neutron generation targets are utilized for BNCT, and the characteristics comparison of these two are analyzed. On the newly constructed BNCT research platform in China, new boron drug research and development work are conducted in many institutes, universities and pharmacy companies. And in recent, a new AB-BNCT facility is under construction for clinic trails in a hospital. So we can have an optimistic viewpoint for BNCT future in China.

Study of the upper energy limit of useful epithermal neutrons for Boron Neutron Capture Therapy in different tissues

In Boron Neutron Capture Therapy (BNCT), the IAEA recommendations limit the epithermal range to 10 keV. Few works have shown the possibility to increase this limit. In particular, in a previous work we showed this possibility by means of simulations of the dose on a simple phantom of a 4-component ICRU tissue. This possible increment is very relevant for the future accelerator-based neutron sources for BNCT. The present work is based on more realistic MCNP6.2 simulations at neck, brain and abdomen. Several parameters and Figures of Merit have been evaluated for different beam apertures and beam divergences. The results show that neutrons above 10 keV can be useful for BNCT. The exact limit of the epithermal range depends on the location of the tumor.

High heat removal technique for a lithium neutron generation target used for an accelerator-driven BNCT system

Accelerator-driven neutron sources have been developed worldwide for boron neutron capture therapy (BNCT) instead of nuclear reactors. Nagoya University is currently developing a compact DC accelerator driven BNCT system using a sealed lithium (Li) target. The target receives a high heat load by a proton beam, and the heat then requires efficient removal. This study developed a high-efficiency heat removal technique that uses V-shaped staggered ribs on the heat removal side of the flow channels. We performed experiments using an electron beam to confirm the technique performance. The results showed double the heat removal performance compared to the smooth surface channel. The value expected to sufficiently remove 6.6 MW/m2 of heat load provided by the proton beam at the Nagoya University neutron source for BNCT.

Technical feasibility study of BAEC TRIGA reactor (BTRR) as a neutron source for BNCT using OpenMC Monte Carlo code

Cancer treatment is a challenging task in the medical field around the world. Most of the cases of the treatment procedures often have limitations and harmful side effects. Boron Neutron Capture Therapy (BNCT) is a method of cancer treatment where it is found to be less toxic and more effective in some form of tumor cells. BNCT requires a neutron beam, and a research reactor is the most reliable source of it. This study is about the technical feasibility of the Bangladesh Atomic Energy Commission TRIGA research reactor (BTRR) used as a neutron source for BNCT. The BTRR reactor has three irradiation sites (2 beam tubes (BTs), and a thermal column) currently unutilized. This study checks the technical feasibility of BNCT treatment neutron beam requirements (epithermal beam) in different external irradiation sites of the reactor. Monte Carlo simulation toolkit OpenMC was used to carry out the reactor model and flux calculation. It was found that the thermal column would be the best place to house the patient for the treatment. An epithermal flux of 1.0E+09 is available about halfway into the thermal column graphite.

Diffusion bonded Be neutron target using 8MeV proton beam

The development of the high intensity compact neutron source is mainly conducted by using accelerators for medical purposes. Recently, a lot of compact neutron sources have been developed, and most of them are for boron neutron capture therapy (BNCT). Compared with the common accelerators used for industries, accelerators for BNCT have to accelerate a 100 times larger current of charged particles because of the low conversion efficiency of neutron moderators. To attain a reliable target for the BNCT neutron source, two obstacles have to be overcome; radiation damage (blistering) and heat issue. We introduce diffusion bonding method aiming to make defect free Be neutron target and 1 MPa latent heat water-cooling system. We also install beam expansion optics using quadrupole and octupole magnets to reduce the charge density. Our facility has been operating for more than three years from the commissioning period and we report the recent situation as following. 1) Diffusion bonding method was applied to the solid neutron target of Be with latent heat cooling system. 2) Amount of integrated coulomb value of protons implanted to the Be target is nearly 3000 C now 3) Amount of neutron dose rate was measured. 4) A laser reflection microscope (LRM) method has been developed to observe the neutron target condition (especially radiation damage) through viewport with a few meters working distance. 5) Direct observation of the surface of the Be target was done during the period of improving nearly target vacuum and residual radiation conditions. From these evidences, we conclude our neutron target already produces neutrons capable to treat nearly 500 patients of malignant melanoma.

Feasibility study on the use of 230MeV proton cyclotron in proton therapy centers as a spallation neutron source for BNCT.

The feasibility of using 230MeV proton cyclotrons in proton therapy centers as a spallation neutron source for Boron Neutron Capture Therapy (BNCT) was investigated. BNCT is based on the neutron irradiation of a 10B-containing compound located selectively in tumor cells. Among various types of neutron generators, the spallation neutron source is a unique way to generate high-energy and high-flux neutrons. Neutron beam was generated by a proton accelerator via spallation reactions and then the produced neutron beam was shaped to be appropriate for BNCT. The proposed Beam Shaping Assembly (BSA) consists of different moderators, a reflector, a collimator, as well as thermal and gamma filters. In addition, the simulated Snyder head phantom was utilized to evaluate the dose distribution in tumor and normal tissue due to the irradiation by the designed beam. MCNPX2.6 Monte Carlo code was used to optimize BSA as well as evaluate dose evaluation. A BSA was designed. With the BSA configuration and a beam current of 104nA, epithermal neutron flux of 3.94×106 [n/cm2] can be achieved, which is very low. Provided that we use the beam current of 5.75μA, epithermal neutron flux of 2.18×108 [n/cm2] can be obtained and the maximum dose of 38.2 Gy-eq can be delivered to tumor tissue at 1.4cm from the phantom surface. Results for 230MeV protons show that with proposed BSA, proton beam current about 5.75μA is required for this purpose.

Investigating a proton beam-based neutron source for BNCT using the MCNP simulation

Works in this project are focused on the design and optimization of a beam shaping assembly (BSA) for boron neutron capture therapy (BNCT) based on a 30 MeV proton beam generator. The aim was to maximize the epithermal neutron flux and to prevent the background radiation which are required for the BNCT designation. A set of material and geometry simulations of neutron multiplier, moderator, reflector, and collimator was examined. The final configuration consists of 0.5 cm of beryllium as a p-n converter, 15 cm in radius of uranium as a neutron multiplier, 44 cm of TiF3 and 15 cm of Al2O3 as a first and second layer of moderator, 10 cm thickness of lead as a reflector, and lithium polyethylene as a collimator. According to the results of the calculation, the proposed cylinder BSA provides high epithermal neutron flux at the irradiation area.

P268] Monte Carlo study of photoneutrons from flattened filter free medical linear accelerator for BNCT applications

Purpose Studies in Italy have indicated the possibility of using photo-neutrons from high energy linac as a promising alternative neutron source to obtain intense neutron fluence rate for Boron Neutron Capture Therapy (BNCT) applications [1] . In continuation to these efforts, this study was carried out with aims: 1) to select high intensity linear accelerator that can be used for photo-neutron production; 2) to select the best materials for photo-neutron production. Methods Initially, photon planner fluence and photons distributions have been simulated for a range of medical linear accelerators to study photon intensity using BEAMnrc Monte Carlo code. Due to its high photon intensity, The FFF Linac was selected as a nominal source to study photo-neutrons. Monte Carlo Simulations were then performed for photo-neutrons production from flattening filter free (FFF) medical Linac using lead and tungsten convertors. Results Our results showed that photo-neutrons flux and yield increase with both photon energy and convertor thickness, saturating at 7 cm (lead) and 6 cm (tungsten) convertors. The average photoneutrons energy produced ranged from 0.480 to 0.863 MeV for the tungsten convertor and from 0.586 to 1.214 MeV for the lead convertor. A photoneutrons flux of 3.971 × 10 8 n/cm2s and 2.585 × 10 8 n/cm2s have been calculated for a 25 MeV medical linac equipped with 7 cm lead convertor and 6 cm tungsten convertor respectively. Conclusions In conclusion the FFF linac presented a considerable feasibility toward having it as an alternative neutron source for BNCT with lead and tungsten as a suitable photoconverters.

Detail Engineering Design of Compact Neutron Generator to Support BNCT Facility in Indonesia

Boron Neutron Capture Therapy (BNCT) is a method of cancer therapy based on neutron radiation which has advantages over the other cancer therapy methods. It uses a stable isotope of 10B which will be an excited isotope of 11B when irradiated by thermal neutron. It immediately (in 10-12 s) breaks into α particle and a lithium recoil nucleus. The two secondary particles play important roles in killing cancer cells. They have a short range in tissue (5 µm and 9 µm respectively) which is less than the average dimension of a cell. This leads to the damage of cancer cell only but the normal cells remain safe. Thermal and epithermal neutrons play important roles in BNCT. From the beginning the neutron sources for BNCT are nuclear reactors which produce high intensity of thermal neutrons (En &lt;0.5 eV), epithermal neutrons (0.5 eV&lt; En &lt; 10 keV) and fast neutrons (En &gt; 10 keV). However, nuclear reactors are very expensive and too large to be used in hospitals. In addition, the operation of nuclear reactors is under restricted protocols related to safety and physical protection. A compact neutron generator is a good choice of neutron source for BNCT. The advantages of compact neutron generator are that the size is small and that the neutron yield is more than 109 ns-1 which satisfies the requirement recommended by IAEA. Additionally, the neutron energy is not so high that it requires a complicated neutron collimator, the operation is easy, and the public acceptance is higher than with nuclear reactors. Based on the requirements of epithermal neutron beam for BNCT facility, the detailed engineering design of compact neutron generator has been made.

A brief review on reactor-based neutron sources for boron neutron capture therapy

Neutron sources for boron neutron capture therapy (BNCT) have been based, until few years ago, on fission nuclear reactors; indeed only nuclear reactors were able to produce neutron flux with the right intensity in the range of thermal and/or epithermal energy. At present many centers are substituting reactor sources with accelerator-based neutron sources that can be easily installed in a hospital environment helping the BNCT diffusion as a standard cancer treatment. Although only few reactor-based BNCT sources are still active (Argentine, China, Japan, Taiwan), nonetheless the role played by nuclear reactors was essential for BNCT birth, and the current available reactors will continue to give a fundamental contribution to its further development. In this article we report a brief review of the fission reactor-based neutron sources for BNCT; we focus on the main requirements which this source had to fulfil to be suitable for BNCT applications, not pretending to be exhaustive due to the very broad topic. General requirements for reactor BNCT neutron sources, techniques to produce epithermal neutron beams starting from fission neutrons, and parameters for their performance evaluation will be briefly discussed.

A review of the development of In-Hospital Neutron Irradiator-1 and boron neutron capture therapy clinical research on malignant melanoma

Boron neutron capture therapy (BNCT) is a binary targeting radiation therapeutic modality. Neutron source is one of the basic conditions of BNCT research. Specially designed neutron source, which could be set in hospital, is needed urgently for doctors and researchers. China research group has developed In-Hospital Neutron Irradiator-1 (IHNI-1), which is a specially designed reactor-based neutron source for BNCT with thermal power 30 kW and suitable for hospital siting. IHNI-1 has highly efficient neutron beams for both shallow and deep tumor irradiation and has the features of inherent safety, low power, small size, long-time stable, easy and quick operation, environment-friendly and low investment for construction and maintain. This paper gives a review of the development of IHNI-1, including the structure introduction and main test operation result, characterization neutron beams and finally reviews on the first BNCT clinical research at IHNI-1.

Performance verification of an epithermal neutron flux monitor using accelerator-based BNCT neutron sources

The performance of an epithermal neutron flux monitor developed for boron neutron capture therapy (BNCT) is verified by Monte Carlo simulations using accelerator-based neutron sources (ABNSs). The results indicate that the developed epithermal neutron flux monitor works well and it can be efficiently used in practical applications to measure the epithermal neutron fluxes of ABNSs in a high accuracy.

Monte Carlo optimization of an epithermal neutron flux monitor for BNCT

ABSTRACTAn epithermal neutron (0.5 eV < En < 10 keV) flux monitor developed for boron neutron capture therapy (BNCT) was optimized by Monte Carlo simulations. Based on this optimization study, the optimization results for each component of the epithermal neutron flux monitor were obtained. The simulation results indicated that the epithermal neutron flux monitor with optimal configuration was more efficiently applicable to precisely measure the epithermal neutron fluxes of BNCT neutron sources.