Accelerator-based Neutron Source Research Articles

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.

In Vivo Accelerator-Based Boron Neutron Capture Therapy for Spontaneous Tumors in Large Animals: Case Series.

Simple SummaryAccelerator-based neutron sources for boron neutron capture therapy (BNCT) are potentially more accessible than nuclear reactors but many technical issues in clinical trials and further routine therapy remain to be studied. We aim to broaden the understanding of these issues with a study of BNCT in 10 cats and dogs, highlighting practical issues, using an accelerator-based neutron source. Using larger animals with tumors mimicking human clinical progression is an important intermediate step to clinical BNCT development.(1) Background: accelerator-based neutron sources are a new frontier for BNCT but many technical issues remain. We aimed to study such issues and results in larger-animal BNCT (cats and dogs) with naturally occurring, malignant tumors in different locations as an intermediate step in translating current research into clinical practice. (2) Methods: 10 pet cats and dogs with incurable, malignant tumors that had no treatment alternatives were included in this study. A tandem accelerator with vacuum insulation was used as a neutron source. As a boron-containing agent, 10B-enriched sodium borocaptate (BSH) was used at a dose of 100 mg/kg. Animal condition as well as tumor progression/regression were monitored. (3) Results: regression of tumors in response to treatment, improvements in the overall clinical picture, and an increase in the estimated duration and quality of life were observed. Treatment-related toxicity was mild and reversible. (4) Conclusions: our study contributes to preparations for human BNCT clinical trials and suggests utility for veterinary oncology.

Importance of radiobiological studies for the advancement of boron neutron capture therapy (BNCT).

Boron neutron capture therapy (BNCT) is a tumour selective particle radiotherapy, based on the administration of boron carriers incorporated preferentially by tumour cells, followed by irradiation with a thermal or epithermal neutron beam. BNCT clinical results to date show therapeutic efficacy, associated with an improvement in patient quality of life and prolonged survival. Translational research in adequate experimental models is necessary to optimise BNCT for different pathologies. This review recapitulates some examples of BNCT radiobiological studies for different pathologies and clinical scenarios, strategies to optimise boron targeting, enhance BNCT therapeutic effect and minimise radiotoxicity. It also describes the radiobiological mechanisms induced by BNCT, and the importance of the detection of biomarkers to monitor and predict the therapeutic efficacy and toxicity of BNCT alone or combined with other strategies. Besides, there is a brief comment on the introduction of accelerator-based neutron sources in BNCT. These sources would expand the clinical BNCT services to more patients, and would help to make BNCT a standard treatment modality for various types of cancer. Radiobiological BNCT studies have been of utmost importance to make progress in BNCT, being essential to design novel, safe and effective clinical BNCT protocols.

Numerical investigation of spallation neutrons generated from petawatt-scale laser-driven proton beams

Laser-driven neutron sources could offer a promising alternative to those based on conventional accelerator technologies in delivering compact beams of high brightness and short duration. We examine this through particle-in-cell and Monte Carlo simulations that model, respectively, the laser acceleration of protons from thin-foil targets and their subsequent conversion into neutrons in secondary lead targets. Laser parameters relevant to the 0.5 PW LMJ-PETAL and 0.6–6 PW Apollon systems are considered. Owing to its high intensity, the 20-fs-duration 0.6 PW Apollon laser is expected to accelerate protons up to above 100 MeV, thereby unlocking efficient neutron generation via spallation reactions. As a result, despite a 30-fold lower pulse energy than the LMJ-PETAL laser, the 0.6 PW Apollon laser should perform comparably well both in terms of neutron yield and flux. Notably, we predict that very compact neutron pulses, of ∼10 ps duration and ∼100 μm spot size, can be released provided the lead convertor target is thin enough (∼100 μm). These sources are characterized by extreme fluxes, of the order of 1023 n cm−2 s−1, and even ten times higher when using the 6 PW Apollon laser. Such values surpass those currently achievable at large-scale accelerator-based neutron sources (∼1016 n cm−2 s−1), or reported from previous laser experiments using low-Z converters (∼1018 n cm−2 s−1). By showing that such laser systems can produce neutron pulses significantly brighter than existing sources, our findings open a path toward attractive novel applications, such as flash neutron radiography and laboratory studies of heavy-ion nucleosynthesis.

Cobaltabis(dicarbollide) ([o-COSAN]-) as Multifunctional Chemotherapeutics: A Prospective Application in Boron Neutron Capture Therapy (BNCT) for Glioblastoma.

Simple SummaryGlioblastoma multiforme (GBM) is one of the most common malignant brain tumors. Although a variety of GBMs is initially susceptible to chemotherapy, the development of multi-drug resistance and recurrence is frequent. Therefore, there is an urgent need for more efficient treatment modalities for GBM. Boron neutron capture therapy (BNCT) is a cancer therapy based on the potential of 10B atoms to produce α particles that cross tissues in which the 10B accumulates without damaging the surrounding healthy tissues after irradiation with low energy thermal neutrons. The aim of our study was to assess that the sodium salt of cobaltabis(dicarbollide) and its di-iodinated derivative could be good candidates for dual anti-cancer treatment (chemotherapy + BNCT). Our results strongly suggest that these small molecules, in particular [8,8′-I2-o-COSAN]−, are serious candidates to be taken into account for BNCT now that the accelerator-based neutron source facilities are more accessible, providing an alternative treatment for resistant glioblastoma.Purpose: The aim of our study was to assess if the sodium salt of cobaltabis(dicarbollide) and its di-iodinated derivative (Na[o-COSAN] and Na[8,8′-I2-o-COSAN]) could be promising agents for dual anti-cancer treatment (chemotherapy + BNCT) for GBM. Methods: The biological activities of the small molecules were evaluated in vitro with glioblastoma cells lines U87 and T98G in 2D and 3D cell models and in vivo in the small model animal Caenorhabditis elegans (C. elegans) at the L4-stage and using the eggs. Results: Our studies indicated that only spheroids from the U87 cell line have impaired growth after treatment with both compounds, suggesting an increased resistance from T98G spheroids, contrary to what was observed in the monolayer culture, which highlights the need to employ 3D models for future GBM studies. In vitro tests in U87 and T98G cells conclude that the amount of 10B inside the cells is enough for BNCT irradiation. BNCT becomes more effective on T98G after their incubation with Na[8,8′-I2-o-COSAN], whereas no apparent cell-killing effect was observed for untreated cells. Conclusions: These small molecules, particularly [8,8′-I2-o-COSAN]−, are serious candidates for BNCT now that the facilities of accelerator-based neutron sources are more accessible, providing an alternative treatment for resistant glioblastoma.

Boron neutron capture therapy in clinical application:Progress and prospect

<p indent="0mm">Boron neutron capture therapy (BNCT) is an emerging radiotherapeutic modality aimed at selectively concentrating boron compounds in tumor cells and then subjecting the tumor cells to neutron beam radiation. Treatment with BNCT is based on the nuclear capture and fission reactions that occur when nonradioactive boron-10 (¹⁰B) is irradiated with neutrons to yield an alpha particle (helium, ⁴He) and a recoiling lithium-7 (⁷Li) nuclei. The ⁴He particle has a range of <sc>9 μm</sc> and the ⁷Li particle <sc>5 μm</sc> in tissue. In theory, the short range of this reaction limits the damage to malignant cells while sparing adjacent normal cells. The development of BNCT is still constrained by the progress in developing boron delivery agents with a high tumor uptake, low normal tissue uptake, and optimizing the dosing paradigms and quantitative estimation of the ¹⁰B concentrations. It is widely recognized that the second generation boron-containing agents, sodium borocaptate (BSH) and boronophenylalanine (BPA), are less than ideal. New and more effective boron-containing agents are urgently required for clinical use to deliver the requisite amounts of boron to tumor cells. The delivery of boron-containing agent can also be optimized to improve cancer cell uptake and subcellular distribution. Additionally, it is crucial to design high intensity neutron sources and establish hospital-based BNCT. Compared with nuclear reactors, accelerator-based neutron sources are more realistic to be applied in clinical practice. In future, the critical issues regarding novel boron-containing agents, the appropriate delivery strategies, and neutron sources of BNCT for clinical use must be addressed. Two clinical trials with newly diagnosed glioblastoma have been reported, BNCT alone after surgery provided a mean survival time of 17.7 and <sc>19.5 months</sc> respectively. The survival outcomes were good as compared to the current standard of care which is post-operation fractionated radiotherapy with concomitant and adjuvant TMZ. Several clinical studies of BNCT in the treatment of recurrent head and neck cancer have been reported, with high response rate and acceptable toxicity. To date, BNCT has been clinically evaluated as an alternative to conventional radiotherapy for the treatment of several tumor types, including newly diagnosed glioblastoma, recurrent glioma, recurrent head and neck tumors, meningioma, malignant melanoma, and liver metastasis. Recently, accelerator-based neutron source has been used in clinical trials for recurrent malignant gliomas and head &amp; neck cancers. Although initial results with BNCT are promising, high-quality prospective clinical trials are still lacking. Well-designed phase II/III clinical research is necessary to define the efficacy and safety of BNCT in various tumor types. Meanwhile, studies comparing the outcomes of BNCT with other standards of care are needed for the further development of BNCT. Based on the previous studies, the BNCT clinical trials in glioblastoma can be initiated with newly diagnosed glioblastoma patients. For other tumor types, late-stage patients with recurrent or metastatic disease after the first-line treatment might be recruited. Last but not the least, in the era of comprehensive treatment for malignant tumor, it is necessary to explore the combined treatment mode of BNCT. For the future research, BNCT may be coupled with a variety of anti-tumor modalities, including traditional photon radiotherapy, immunotherapy, targeted therapy and chemotherapy. It is also possible to explore a variety of drug delivery methods to improve the uptake of boron-containing agents by tumor sites. Multidisciplinary model is needed to jointly promote BNCT to become a routine clinical treatment modality.

RTID-07. AN INVESTIGATOR-LEAD PHASE II CLINICAL TRIAL OF ACCELERATOR-BASED BNCT FOR REFRACTORY AND RECURRENT HIGH-GRADE MENINGIOMA

Abstract BACKGROUD Boron neutron capture therapy (BNCT) is tumor-selective particle radiation. We applied this unique technique and achieved excellent clinical results for recurrent and refractory high-grade meningiomas (HGM) using reactor neutron sources (Neuro-Oncology, in press, doi:10.1093/neuonc/noab108). Recently accelerator-based neutron sources (ABNS) was approved for medical device in Japan for refractory H&amp;N cancers. PURPOSES Based on these situations, we proposed “A phase II clinical trial using accelerator-based BNCT system for refractory recurrent HGM” for AMED in Japan which is similar to NIH in USA. This proposal was successfully accepted. DESIGN We prepared 2 study groups, BNCT test treatment group and control best supportive care group, for RCT. PFS and OS were set-up as primary and secondary endpoints, respectively. Rescue BNCT is allowed for control group patients, if they showed PD during observation. The trial started in August 2019. METHODS Twelve BNCT and 6 control subjects will be included. Patients’ eligibility criteria is recurrent HGM after some radiotherapy. Cyclotron-based ABNS system is used for neutron source. Neutron-irradiation time is determined not to exceed to 7.5 Gy-Eq for scalp dose which was referencing preceding phase I trial for malignant gliomas. PROGRESS As of March 2021, 13 subjects were included, 9 for BNCT treatment group, 4 for control best supportive care group. All 4 control subjects showed PD during 2 months while 8 out of 9 subjects showed SD or PR during observation period and there is a statistical significance in both groups, by Log-rank and Wilcoxon analyses with p=0.0012 and 0.0020, respectively. CONCLUSION We started this RCT and will introduce the interim report of this clinical trial in the meeting. At the SNO meeting we will present further detail of this trial.

Dose-Dependent Suppression of Human Glioblastoma Xenograft Growth by Accelerator-Based Boron Neutron Capture Therapy with Simultaneous Use of Two Boron-Containing Compounds.

Simple SummaryAccelerator-based boron neutron capture therapy (BNCT) has opened up new perspectives in increasing cancer treatment efficacy, including malignant brain tumors and particularly glioblastoma. We studied dosimetry control optimization, neutron beam parameter adjustment, and two boron compound combinations (along with single and double irradiation regimens) to assess safety and increase therapy efficacy, using a U87MG xenotransplant immunodeficient mouse model. In two sets of experiments, we achieved increases in tumor-growth inhibition (to 80–83%), a neutron capture therapy ratio of 2:1 (two times higher neutron capture therapy efficacy than neutron irradiation without boron), and increases in animal life expectancy, from 9 to 107 days, by treatment parameter adjustment. These results will contribute to the development of clinical-trial protocols for accelerator-based BNCT and further innovations in this cancer treatment method.(1) Background: Developments in accelerator-based neutron sources moved boron neutron capture therapy (BNCT) to the next phase, where new neutron radiation parameters had to be studied for the treatment of cancers, including brain tumors. We aimed to further improve accelerator-BNCT efficacy by optimizing dosimetry control, beam parameters, and combinations of boronophenylalanine (BPA) and sodium borocaptate (BSH) administration in U87MG xenograft-bearing immunodeficient mice with two different tumor locations. (2) Methods: The study included two sets of experiments. In Experiment #1, BPA only and single or double irradiation in higher doses were used, while, in Experiment #2, BPA and BSH combinations and single or double irradiation with dosage adjustment were analyzed. Mice without treatment or irradiation after BPA or BPA+BSH injection were used as controls. (3) Results: Irradiation parameter adjustment and BPA and BSH combination led to 80–83% tumor-growth inhibition index scores, irradiation:BNCT ratios of 1:2, and increases in animal life expectancy from 9 to 107 days. (4) Conclusions: Adjustments in dosimetry control, calculation of irradiation doses, and combined use of two 10B compounds allowed for BNCT optimization that will be useful in the development of clinical-trial protocols for accelerator-based BNCT.

Feasibility of Prompt Gamma Ray Detection and Imaging Using CdTe Detectors for BNCT ― Monte Carlo Study

Boron neutron capture therapy (BNCT) has experienced a renaissance in recent years, due to the availability of accelerator-based neutron sources and more effective delivery vehicles of boron-10 (10B). For successful BNCT, 10B concentration and distribution in the tumor (as well as in the critical organs) must be determined non-invasively prior to BNCT treatments. While conventional nuclear imaging (e.g., PET/SPECT), in conjunction with radiolabeled 10B, may serve for this purpose, another approach, based on the detection of prompt gamma (PG) rays from the BNC reaction, appears to be more attractive, most notably because it can be implemented within the BNCT setup without radiolabeling of 10B. The detectability of PG rays (478 keV) from the BNC reaction has been shown experimentally within the context of BNCT utilizing energy-resolving solid-state detectors. However, the feasibility of this approach under the clinically relevant conditions is currently unknown. Thus, the present work investigated this feasibility by performing Monte Carlo (MC) simulations using the simulation toolkit.MC models of various phantom cases were created to simulate epithermal neutron beam irradiation relevant to accelerator-based BNCT (a-BNCT). For benchmarking and future experimental verification, the phantom geometry (20 cm-diameter/24 cm-height cylinder) and material (PMMA) were chosen based on a published experimental study. The phantom had 3 cm-diameter/3.8 cm-height cylindrical inserts (located at 5 cm depth along the long-axis of the phantom) that contained 10B solution at different concentrations ranging from 1 - 30,000 parts-per-million (ppm). For detection of PG rays, a 23.1 cm-diameter ring detector consisting of 120 cadmium telluride (CdTe) crystals was modeled. CdTe was chosen because of its high photon counting efficiency and energy resolution. Each CdTe detector crystal (5 × 5 × 1 mm3) contained an inherent 0.1mm-thick beryllium window and a novel/custom thermal neutron filter made of gadolinium. Two billion incident neutron histories were used during each MC simulation. The detected PG ray signals were used to test both direct mapping and CT techniques for quantitative imaging.The current MC simulations showed PG ray signals from the10B-loaded tumor-mimicking cylindrical insert were above the background noise (with a 95% confidence level), down to the clinically achievable tumor 10B concentration of 30 ppm. The custom thermal neutron filter was effective in suppressing the inherent background from CdTe detectors.This MC study demonstrated the detectability of PG rays from the BNC reaction using CdTe detectors under the conditions closely mimicking realistic a-BNCT scenarios. It also showed that clinically acceptable quantitative imaging of 10B distribution could be performed utilizing the PG ray signals from the BNC reaction.H. Moktan: None. C. Lee: None. S. Cho: Research Grant; TAE Life Sciences.

Status of development and planning activities on CANS in Korea

This report reviews the overall status of the development and planning activities of compact accelerator-based neutron sources in Korea. For the last decade, the demand for the technology development and application of CANS has significantly increased, and becomes widely accepted by the science, engineering and industry sectors. Since the first technical workshop focused on CANS under the support of the Korea Nuclear Society in fall 2016, there have been numerous efforts to launch projects by several groups. Although unsuccessful, two CANS projects were newly launched in 2020. One is the 30-MeV cyclotron-based neutron source for industrial neutron imaging at the Korea Atomic Energy Research Institute (KAERI), and the other is the BNCT technology development at the Korea Institute of Radiological &amp; Medical Sciences. A project proposal for an expansion of the proton LINAC facility at KAERI to 200 MeV for semiconductor irradiation testing through the produced neutron field is now almost complete and will be submitted to the government funding agency for review. The CANS project for BNCT based on the proton LINAC developed by the Dawonsys consortium is briefly described. The new neutron source based on electron LINAC is prepared by the Pohang Light Source laboratory, and the initial consideration and application targets are also described. A new strategic plan for national R&amp;D on radiation technology and the enforcement of its infrastructure is still under way, and a more systematic approach to the development and application of neutron sources will be implemented through the strategic planning.

A prototype compact accelerator-based neutron source (CANS) for Canada

Canada’s access to neutron beams for neutron scattering was significantly curtailed in 2018 with the closure of the National Research Universal (NRU) reactor in Chalk River, Ontario, Canada. New sources are needed for the long-term; otherwise, access will only become harder as the global supply shrinks. Compact Accelerator-based Neutron Sources (CANS) offer the possibility of an intense source of neutrons with a capital cost significantly lower than spallation sources. In this paper, we propose a CANS for Canada. The proposal is staged with the first stage offering a medium neutron flux, linear accelerator-based approach for neutron scattering that is also coupled with a boron neutron capture therapy (BNCT) station and a positron emission tomography (PET) isotope production station. The first stage will serve as a prototype for a second stage: a higher brightness, higher cost facility that could be viewed as a national centre for neutron applications.

GEANT4 simulations of the neutron beam characteristics for 9Be/7Li targets bombarded by the low energy protons

9Be(p,xn) and 7Li(p,xn) are two reactions for the accelerator-based compact neutron source at low energy protons conditions, especially for BNCT facilities and it is necessary to simulate the beam characteristics accurately. The different reference physics lists recommended by GEANT4 have been used to calculate the neutron beam characteristics for the 9Be and 7Li targets bombarded by proton beams of 5 ∼ 10 MeV and the accuracy of GEANT4 simulations has been discussed. By comparing with the reference data such as experimental data, MCNP6 simulations and numerical calculations, the results calculated by QGSP_BIC_AllHP show good agreement with a relative error of less than 10%. The neutron yields level out and have a tendency to move forward, when the thickness is greater than the range of protons in targets. However, the neutron yields are significantly underestimated by other physics lists except for QGSP_BIC_AllHP. In addition, two fitted curve equations are acquired to quickly estimate the neutron yield for 9Be and 7Li targets below 20 MeV. Therefore, due to the limitation of the particle type and energy range in this study, GEANT4 with QGSP_BIC_AllHP is recommended to calculate hadronic interactions of protons with matter below 20 MeV.

Measurement of Parameters of Neutron Radiation on the Accelerator-Based Epithermal Neutron Source

Measurement of Parameters of Neutron Radiation on the Accelerator-Based Epithermal Neutron Source

Time-resolved secondary triton burnup 14 MeV neutron measurement by a new scintillating fiber detector in middle total neutron emission ranges in deuterium large helical device plasma experiments

A middle-sensitivity scintillating fiber detector (hereafter middle Sci-Fi detector) that works at a deuterium-tritium neutron flux of ~105-107 cm−2s−1 was utilized to measure secondary deuterium-tritium neutron emission rates with high temporal resolution at a total neutron emission rate of 1013 to 1015 n/s, where strong magnetohydrodynamic (MHD) instabilities were observed in the large helical device deuterium plasma experiments. The gain and angular characteristics of the middle Sci-Fi detector were evaluated in an accelerator-based deuterium-tritium neutron source in the intense 14 MeV neutron source facility at Osaka University. Observation of 1 MeV triton transport due to MHD instability was performed by a middle Sci-Fi detector whose deuterium-tritium neutron counting rate was approximately 20 times higher than that of the conventional Sci-Fi detector. Fusion-born triton transport due to energetic-particle-driven MHD instability was observed using the middle Sci-Fi detector due to its high detection efficiency and high discrimination ability of deuterium-tritium neutrons from the sea of deuterium-deuterium neutrons.

The Measurement of the Neutron Yield of the 7Li(p,n)7Be Reaction in Lithium Targets

Simple SummaryA compact neutron source has been proposed and created at the Budker Institute of Nuclear Physics in Novosibirsk, Russia. The source comprises an original design tandem accelerator, solid lithium target, and a neutron beam shaping assembly. The neutron source is capable of producing the high neutron flux for boron neutron capture therapy (BNCT). Currently, the BNCT technique has entered into clinical practice in the world: two clinics began treating patients, and four more BNCT clinics are ready to start operating. The neutron source proposed at the Budker Institute served as a prototype for a facility created for a clinic in Xiamen (China). It is planned to equip the National Medical Research Center of Oncology (Moscow, Russia) and National Oncological Hadron Therapy Center (Pavia, Italy) with the same neutron sources. Due to the impending use of an accelerator neutron source for treating patients, the validation of the neutron yield of the 7Li(p,n)7Be reaction in lithium metal targets is required. The theoretical neutron yield has not been evaluated experimentally so far.A compact accelerator-based neutron source has been proposed and created at the Budker Institute of Nuclear Physics in Novosibirsk, Russia. An original design tandem accelerator is used to provide a proton beam. The neutron flux is generated as a result of the 7Li(p,n)7Be threshold reaction using the solid lithium target. A beam shaping assembly is applied to convert this flux into a beam of epithermal neutrons with characteristics suitable for BNCT. The BNCT technique is being tested in in vitro and in vivo studies, and dosimetry methods are being developed. Currently, the BNCT technique has entered into clinical practice in the world: after successful clinical trials, two clinics in Japan began treating patients, and four more BNCT clinics are ready to start operating. The neutron source proposed at the Budker Institute of Nuclear Physics served as a prototype for a facility created for a clinic in Xiamen (China). It is planned to equip the National Medical Research Center of Oncology (Moscow, Russia) and National Oncological Hadron Therapy Center (Pavia, Italy) with the same neutron sources. Due to the impending use of an accelerator neutron source for treating patients, the validation of the neutron yield of the 7Li(p,n)7Be reaction in lithium metal targets is required. The theoretical neutron yield has not been evaluated experimentally so far.

Compact ultracold neutron source concept for low-energy accelerator-driven neutron sources

The concept of a small-scale, pulsed-proton accelerator-based compact ultracold neutron (UCN) source is presented. The essential idea of the compact UCN source is to enclose a volume of superfluid \(^{4}\hbox {He}\) converter with a supercold moderator in the vicinity of a low-radiation neutron production target from (p, n) reactions. The supercold moderator should possess an ability to produce cold neutron flux with a peak brightness near the single-phonon excitation band of the superfluid \(^{4}\hbox {He}\) converter, thereby augmenting the UCN production in the compact UCN source even with very low intensity of neutron brightness. The performance of the compact UCN source is studied in terms of the UCN production and thermal load in the UCN converter. With the proposed concept of the compact UCN source, a UCN production rate of \(P_\mathrm{{UCN}}=80\,\hbox {UCN/cm}^{3}/\hbox {s}\) in the UCN converter could be obtained while maintaining thermal load of the superfluid \(^{4}\hbox {He}\) and its container at a level of \(22~\hbox {mW}\). This study shows that the compact UCN source can produce a high enough density of UCNs at a small-scale, low-energy, pulsed-proton beam facility with reduced efforts on the cooling and radiation protection.

Monte Carlo simulation of proton- and neutron-induced radiation damage in a tantalum target irradiated by 70 MeV protons

Beams of free neutrons are an important probe to analyze the structure and dynamics of condensed matter and are produced at neutron research reactors, neutron spallation sources or compact accelerator-based neutron sources (CANS). An efficient construction of CANS with a maximized neutron yield and brilliance requires reliable knowledge of the consequences of radiation-induced material damage, the predominating bottleneck of a target’s lifetime. In the framework of the Jülich High-Brilliance neutron Source project, the impact of proton- and neutron-induced material damage of a tantalum target was investigated. The Monte Carlo codes FLUKA and SRIM were utilized to extract the number of displacements per atom resulting from atomic rearrangements. The simulations performed distinctly identify the rear of the neutron target as the most vulnerable area, with the protons as main damage contributors. The minor contribution of neutrons is a material-specific phenomenon due to their high mean free path length in tantalum. Numerical results of the simulations served to calculate average and peak damage rates {R}_{mathrm{d}} (dpa/s), both in turn scaled to annual displacement doses for continuous operation in a full power year (dpa/fpy). Supplemented by the literature, a minimum target lifetime tau _{min } of 2.6 years (33 Ah) is concluded.

ASSESSMENT OF THE EFFECT OF BORON NEUTRON CAPTURE THERAPY ON TUMOR CELL LINES AND PRIMARY EMBRYONIC CELL CULTURE

Introduction. Boron neutron capture therapy (bnct) is a promising method for treating tumors, in particular, infiltrative malignant tumors, due to the selective destruction of tumor cells without damaging the surrounding normal tissues. This type of therapy is based on nuclear reaction of neutron capture by stable 10b isotope. For the successful implementation of bnct, boron delivery drugs that must be selectively accumulated in malignant cells in a sufficient amount, and a neutron source with the energy required for the neutron capture reaction are needed. At the budker institute of nuclear physics, the accelerator-based neutron source was designed with flux parameters allowing studies on bnct to be conducted.Objective: to assess the effect of bnct on tumor and normal cell lines using borphenylalanine (bpa), borcaptate (bsh) and liposomal borcaptat as boron delivery drugs.Materials and methods. Human cell cultures: glioblastoma (u87), colorectal human adenocarcinoma (sw-620), human melanoma (sk-mel28) and primary embryonic cell lines were irradiated with a neutron flux at the presence of bpa, bsh and liposomal bsh with a concentration of 10b 40 μg/ml. The short-term cytotoxic effect of irradiation was evaluated using trypan blue. Cell survival 96 hours after irradiation was determined using mtt test, and survival fraction was evaluated using the clonogenic test.Results. Early cytotoxic effects of irradiation were not observed for all 4 cell lines. According to mtt and clonogenic tests, the most pronounced effect of bnct was noticed for sw-620 and u87 lines, regardless of boron delivery drug used. For sk-mel28 line, the best effect was achieved after irradiation with liposomal borocaptate. For the primary transplanted embryonic line, high toxicity was revealed when bnct was performed with borphenylalanine and borcaptate.Conclusion. The data obtained indicate that the accelerator-based bnct using boron delivery drugs, such as borphenylalanine, borcaptate and liposomal borcaptat, has a positive effect on tumor lines of glioblastoma, colorectal adenocarcinoma and melanoma.

Measurement of the 7Li(p,p'γ)7Li reaction cross-section and 478 keV photon yield from a thick lithium target at proton energies from 0.65 MeV to 2.225 MeV

Reliable data on 7Li(p,p'γ)7Li reaction cross section and photon yield from a thick lithium target are important for many applications including boron neutron capture therapy of malignant tumors. Experimental data on cross section differ greatly from one author to another; experimental data on photon yield are extremely scarce. Measurements of the reaction cross section and photon yield were carried out at the accelerator-based neutron source at the Budker Institute of Nuclear Physics (Novosibirsk, Russia) using a NaI and HPGe γ-ray spectrometers. The 7Li(p,p'γ)7Li reaction cross section and 478 keV photon yield from a thick lithium target at proton energies from 0.65 MeV to 2.225 MeV have been measured with high accuracy. The data obtained are presented in the form of tables.

Status of the engineering design of the IFMIF-DONES Central Instrumentation and Control Systems

This work presents the current status of the design of Central Instrumentation and Control Systems for the IFMIF-DONES plant. IFMIF-DONES is the International Fusion Materials Irradiation Facility-DEMO Oriented NEutron Source, an accelerator-based neutron source producing a high-energy deuterons beam focused on a fast flowing liquid lithium jet to generate high-energy neutrons via stripping reactions. The intensity and irradiation volume is suitable to generate material irradiation data for design, licensing, construction and safe operation of the DEMO fusion reactor. After a general overview of the current status of the design of the overall architecture, a particular attention is given to the data management including the EPICS control framework, the general rules and criteria for the design and implementation of the HMI system, and the timing system solution composed of a three-layer distribution network to deliver time at each element of the plant that implements an optimal trade-off between timing performance and cost. Eventually, the next design steps and future work are outlined.