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This study aimed to assess and compare the shielding performance of boron-containing materials for neutrons generated in proton therapy and used in boron neutron capture therapy (BNCT). Five composites, including AlB2, Al-B4C, Al-TiB2, Al-BN, and Al-TiB2-BN, were selected as shielding materials, with concrete used as a benchmark. The mass fraction of boron compounds in these materials ranged from 10% to 50%. The Monte Carlo toolkit Geant4 was employed to calculate shielding parameters, including neutron ambient dose equivalent, dose values, and macroscopic cross-section. Results indicated that, compared to concrete, these boron-containing materials more effectively absorb thermal neutrons. When the boron compound exceeds 30 wt.%, these materials exhibit better shielding performance than concrete of the same thickness for neutrons generated by protons. For a given material, its shielding capability increases with boron content. Among the five materials when the material thickness and boron compound content are the same, the shielding performance for neutrons generated by protons, from best to worst, is as follows: Al-TiB2, Al-B4C, AlB2, Al-TiB2-BN, and Al-BN. For BNCT, the shielding performance from best to worst is in the following order: Al-B4C, AlB2, Al-TiB2, Al-TiB2-BN, and Al-BN. The results of this study provide references and guidelines for the selection and optimization of neutron shielding materials in proton therapy and BNCT facilities. [ABSTRACT FROM AUTHOR]

Boron Neutron Capture Therapy (BNCT) is a cancer treatment which combines tumor-selective boron delivery agents with thermal neutrons in order to selectively eradicate cancer cells. In this work, we focus on the early-stage development of carbohydrate delivery agents for BNCT. In more detail, we expand upon our previous GLUT-targeting approach by synthesizing and evaluating the potential embedded in a representative set of fluorinated carbohydrates bearing a boron cluster. Our findings indicate that these species may have advantages over the boron delivery agents in current clinical use, e.g., significantly improved boron delivery capacity at the cellular level. Simultaneously, the carbohydrate delivery agents were found to bind strongly to plasma proteins, which may be a concern requiring further action before progression to in vivo studies. Altogether, this work brings new insights into factors which need to be accounted for if attempting to develop theranostic agents for BNCT based on carbohydrates in the future. [ABSTRACT FROM AUTHOR]

In the study, the influence of doping apatite-wollastonite (AW) glass-ceramics (GCs) with B 2 O 3 on the structural, physical, microstructural, and light and heavy particle interaction properties is presented. Using the solid-state reaction and the cold isostatic press method, pristine AW, 10 wt% (AW-B10), and 20 wt% (AW-B20) B 2 O 3 -doped AW GCs were prepared. The prepared GCs were subject to structural, chemical compositional, and surface morphological investigation through standard experimental processes. Furthermore, the neutron (fast and thermal) and charged radiation (electron, proton, alpha, and carbon ion) interactional parameters of the GCs were obtained through standard theoretical models and software. The density of AW (2.91 gcm−3) increases to about 2.957 and 2.986 gcm−3 as B 2 O 3 increases to 10 and 20 wt%, respectively. The presence of boron oxide supported the wollastonite phase to remain glass and suppressed crystallisation in the AW GCs. Doping AW with B 2 O 3 improved the interaction probabilities of the GCs with fast and thermal neutrons, electrons, protons, alpha particles, and carbon ions. B-rich AW is thus potentially useful as a target material in human tissues for boron neutron capture therapy for the management of cancer and tumours, isolating or shielding specific tissues in ion beam therapy processes, and other techniques that require the exposure of human tissues to irradiation. [ABSTRACT FROM AUTHOR]

In boron neutron capture therapy (BNCT), boron drugs should exhibit high intratumoral boron concentrations during neutron irradiation, while being cleared from the blood and normal organs. However, it is usually challenging to achieve such tumor accumulation and quick clearance simultaneously in a temporally controlled manner. Here, we developed a polymer-drug conjugate that can actively control the clearance of the drugs from the blood. This polymer-drug conjugate is based on a biocompatible polymer that passively accumulates in tumors. Its side chains were conjugated with the low-molecular-weight boron drugs, which are immediately excreted by the kidneys, via photolabile linkers. In a murine subcutaneous tumor model, the polymer-drug conjugate could accumulate in the tumor with the high boron concentration ratio of the tumor to the surrounding normal tissue (∼10) after intravenous injection while a considerable amount remained in the bloodstream as well. Photoirradiation to blood vessels through the skin surface cleaved the linker to release the boron drug in the blood, allowing for its rapid clearance from the bloodstream. Meanwhile, the boron concentration in the tumor which was not photoirradiated could be maintained high, permitting strong BNCT effects. In clinical BNCT, the dose of thermal neutrons to solid tumors is determined by the maximum radiation exposure to normal organs. Thus, our polymer-drug conjugate may enable us to increase the therapeutic radiation dose to tumors in such a practical situation. [Display omitted] • Pharmacokinetics was actively controlled in a light-responsive manner. • Our system could achieve the high tumor accumulation and T/B ratio simultaneously. • The active control of pharmacokinetics augmented BNCT effects. [ABSTRACT FROM AUTHOR]

Background: In Japan, the clinical treatment of boron neutron capture therapy (BNCT) has been applied to unresectable, locally advanced, and recurrent head and neck carcinomas using an accelerator‐based neutron source since June of 2020. Considering the increase in the number of patients receiving BNCT, efficiency of the treatment planning procedure is becoming increasingly important. Therefore, novel and rapid dose calculation algorithms must be developed. We developed a novel algorithm for calculating neutron flux, which comprises of a combination of a Monte Carlo (MC) method and a method based on the removal‐diffusion (RD) theory (RD calculation method) for the purpose of dose calculation of BNCT. Purpose: We present the details of our novel algorithm and the verification results of the calculation accuracy based on the MC calculation result. Methods: In this study, the "MC‐RD" calculation method was developed, wherein the RD calculation method was used to calculate the thermalization process of neutrons and the MC method was used to calculate the moderation process. The RD parameters were determined by MC calculations in advance. The MC‐RD calculation accuracy was verified by comparing the results of the MC‐RD and MC calculations with respect to the neutron flux distributions in each of the cubic and head phantoms filled with water. Results: Comparing the MC‐RD calculation results with those of MC calculations, it was found that the MC‐RD calculation accurately reproduced the thermal neutron flux distribution inside the phantom, with the exception of the region near the surface of the phantom. Conclusions: The MC‐RD calculation method is useful for the evaluation of the neutron flux distribution for the purpose of BNCT dose calculation, except for the region near the surface. [ABSTRACT FROM AUTHOR]

Background: The out‐of‐field radiation dose for boron neutron capture therapy (BNCT), which results from both neutrons and γ‐rays, has not been extensively evaluated. To safely perform BNCT, the neutron and γ‐ray distributions inside the treatment room and the whole‐body dose should be evaluated during commissioning. Although, certain previous studies have evaluated the whole‐body dose in the clinical research phase, no institution providing BNCT covered by health insurance has yet validated the neutron distribution inside the room and the whole‐body dose. Purpose: To validate the Monte Carlo model of the BNCT irradiation room extended for the whole‐body region and evaluate organ‐at‐risk (OAR) doses using the validated model with a human‐body phantom. Methods: First, thermal neutron distribution inside the entire treatment room was measured by placing Au samples on the walls of the treatment room. Second, neutron and gamma‐ray dose‐rate distributions inside a human‐body water phantom were measured. Both lying and sitting positions were considered. Bare Au, Au covered by Cd (Au+Cd), In, Al, and thermoluminescent dosimeters were arranged at 11 points corresponding to locations of the OARs inside the phantom. After the irradiation, γ‐ray peaks emitted from the samples were measured by a high‐purity germanium detector. The measured counts were converted to the reaction rate per unit charge of the sample. These measurements were compared with results of simulations performed with the Particle and Heavy Ion Transport code System (PHITS). A male adult mesh‐type reference computational phantom was used to evaluate OAR doses in the whole‐body region. The relative biological effectiveness (RBE)‐weighted doses and dose‐volume histograms (DVHs) for each OAR were evaluated. The median dose (D50%) and near‐maximum dose (D2%) were evaluated for 14 OARs in a 1‐h‐irradiation process. The evaluated RBE‐weighted doses were converted to equivalent doses in 2 Gy fractions. Results: Experimental results within 60 cm from the irradiation center agreed with simulation results within the error bars except at ±20, 30 cm, and those over 70 cm corresponded within one digit. The experimental results of reaction rates or γ‐ray dose rate for lying and sitting positions agreed well with the simulation results within the error bars at 8, 4, 11, 7 and 7, 4, 7, 6, 5, 6 out of 11 points, respectively, for Au, Au+Cd, In, Al, and TLD. Among the detectors, the discrepancies in reaction rates between experiment and simulation were most common for Au+Cd, but were observed randomly for measurement points (brain, lung, etc.). The experimental results of γ‐ray dose rates were systematically lower than simulation results at abdomen and waist regions for both positions. Extending the PHITS model to the whole‐body region resulted in higher doses for all OARs, especially 0.13 Gy‐eq increase for D50% of the left salivary gland. Conclusion: The PHITS model for clinical BNCT for the whole‐body region was validated, and the OAR doses were then evaluated. Clinicians and medical physicists should know that the out‐of‐field radiation increases the OAR dose in the whole‐body region. [ABSTRACT FROM AUTHOR]

Background: Boron‐containing compounds, such as 4‐borono‐phenylalanine (BPA) are used as drugs for cancer treatment in the framework of Boron Neutron Capture Therapy (BNCT). Neutron irradiation of boron‐rich compounds delivered to cancer cells triggers nuclear reactions that destroy cancer cells. Purpose: We provide a modeling of the thermal neutron cross section of BPA, a drug used in Boron Neutron Capture Therapy (BNCT), to quantify the competing contributions of boron absorption against hydrogen scattering, for optimizing BNCT by minimizing the latter. Methods: We perform the experimental determination of the total neutron scattering cross section of BPA at thermal and epithermal neutron energies using neutron transmission measurements. We isolate the contribution related to the incoherent scattering by hydrogen atoms as a function of the neutron energy by means of the Average Functional Group Approximation, and we calculate the probability for a neutron of being absorbed as a function of the neutron energy both for BPA and for its variants where either one or all four aromatic hydrogen atoms are substituted by 19F, and both for the samples with natural occurrence or enriched concentration of 10B. Results: While referring to the already available literature for in vivo use of fluorinated BPA, we show that fluorine‐rich variants of BPA increase the probability of neutrons being captured by the molecule. As the higher absorption efficiency of fluorinated BPA does not depend on whether the molecule is used in vivo or not, our results are promising for the higher efficiency of the boron neutron capture treatment. Conclusions: Our results suggest a new advantage using fluorinated compounds for BNCT, in their optimized interaction with neutrons, in addition to their already known capability to be used for monitoring and pharmacokinetics studies using 19F‐Nuclear Magnetic Resonance or in 18F‐Positron Emission Tomography. [ABSTRACT FROM AUTHOR]

Background: Evaluation of the boron dose is essential for boron neutron capture therapy (BNCT). Nevertheless, a direct evaluation method for the boron‐dose distribution has not yet been established in the clinical BNCT field. To date, even in quality assurance (QA) measurements, the boron dose has been indirectly evaluated from the thermal neutron flux measured using the activation method with gold foil or wire and an assumed boron concentration in the QA procedure. Recently, we successfully conducted optical imaging of the boron‐dose distribution using a cooled charge‐coupled device (CCD) camera and a boron‐added liquid scintillator at the E‐3 port facility of the Kyoto University Research Reactor (KUR), which supplies an almost pure thermal neutron beam with very low gamma‐ray contamination. However, in a clinical accelerator‐based BNCT facility, there is a concern that the boron‐dose distribution may not be accurately extracted because the unwanted luminescence intensity, which is irrelevant to the boron dose is expected to increase owing to the contamination of fast neutrons and gamma rays. Purpose: The purpose of this research was to study the validity of a newly proposed method using a boron‐added liquid scintillator and a cooled CCD camera to directly observe the boron‐dose distribution in a clinical accelerator‐based BNCT field. Method: A liquid scintillator phantom with 10B was prepared by filling a small quartz glass container with a commercial liquid scintillator and boron‐containing material (trimethyl borate); its natural boron concentration was 1 wt%. Luminescence images of the boron‐neutron capture reaction were obtained in a water tank at several different depths using a CCD camera. The contribution of background luminescence, mainly due to gamma rays, was removed by subtracting the luminescence images obtained using another sole liquid scintillator phantom (natural boron concentration of 0 wt%) at each corresponding depth, and a depth profile of the boron dose with several discrete points was obtained. The obtained depth profile was compared with that of calculated boron dose, and those of thermal neutron flux which were experimentally measured or calculated using a Monte Carlo code. Results: The depth profile evaluated from the subtracted images indicated reasonable agreement with the calculated boron‐dose profile and thermal neutron flux profiles, except for the shallow region. This discrepancy is thought to be due to the contribution of light reflected from the tank wall. The simulation results also demonstrated that the thermal neutron flux would be severely perturbed by the 10B‐containing phantom if a relatively larger container was used to evaluate a wide range of boron‐dose distributions in a single shot. This indicates a trade‐off between the luminescence intensity of the 10B‐added phantom and its perturbation effect on the thermal neutron flux. Conclusions: Although a partial discrepancy was observed, the validity of the newly proposed boron‐dose evaluation method using liquid‐scintillator phantoms with and without 10B was experimentally confirmed in the neutron field of an accelerator‐based clinical BNCT facility. However, this study has some limitations, including the trade‐off problem stated above. Therefore, further studies are required to address these limitations. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a promising modality for cancer treatment because of its minimal invasiveness. To maximize the therapeutic benefits of BNCT, the development of efficient platforms for the delivery of boron agents is indispensable. Here, carborane‐integrated immunoliposomes were prepared via an exchanging reaction to achieve HER‐2‐targeted BNCT. The conjugation of an anti‐HER‐2 antibody to carborane‐integrated liposomes successfully endowed these liposomes with targeting properties toward HER‐2‐overexpressing human ovarian cancer cells (SK‐OV3); the resulting BNCT activity toward SK‐OV3 cells obtained using the current immunoliposomal system was 14‐fold that of the l‐BPA/fructose complex, which is a clinically available boron agent. Moreover, the growth of spheroids treated with this system followed by thermal neutron irradiation was significantly suppressed compared with treatment with the l‐BPA/fructose complex. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is one of the most appealing radiotherapy modalities, whose localization can be further improved by the employment of boron-containing nanoformulations, but the fabrication of biologically friendly, water-dispersible nanoparticles (NPs) with high boron content and favorable physicochemical characteristics still presents a great challenge. Here, we explore the use of elemental boron (B) NPs (BNPs) fabricated using the methods of pulsed laser ablation in liquids as sensitizers of BNCT. Depending on the conditions of laser-ablative synthesis, the used NPs were amorphous (a-BNPs) or partially crystallized (pc-BNPs) with a mean size of 20 nm or 50 nm, respectively. Both types of BNPs were functionalized with polyethylene glycol polymer to improve colloidal stability and biocompatibility. The NPs did not initiate any toxicity effects up to concentrations of 500 µg/mL, based on the results of MTT and clonogenic assay tests. The cells with BNPs incubated at a 10B concentration of 40 µg/mL were then irradiated with a thermal neutron beam for 30 min. We found that the presence of BNPs led to a radical enhancement in cancer cell death, namely a drop in colony forming capacity of SW-620 cells down to 12.6% and 1.6% for a-BNPs and pc-BNPs, respectively, while the relevant colony-forming capacity for U87 cells dropped down to 17%. The effect of cell irradiation by neutron beam uniquely was negligible under these conditions. Finally, to estimate the dose and regimes of irradiation for future BNCT in vivo tests, we studied the biodistribution of boron under intratumoral administration of BNPs in immunodeficient SCID mice and recorded excellent retention of boron in tumors. The obtained data unambiguously evidenced the effect of a neutron therapy enhancement, which can be attributed to efficient BNP-mediated generation of α-particles. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT), advanced cancer treatment utilizing nuclear fission of 10B atom in cancer cells, is attracting increasing attention. As 10B delivery agent, sodium borocaptate (10BSH, 10B12H11SH ⋅ 2Na), has been used in clinical studies along with L‐boronophenylalanine. Recently, this boron cluster has been conjugated with lipids, polymers or nanoparticles to increase selectivity to and retentivity in tumor. In this work, anticancer nanoformulations for BNCT are designed, consisting of poly(glycerol) functionalized detonation nanodiamonds (DND−PG) as a hydrophilic nanocarrier, the boron cluster moiety (10B12H112−) as a dense boron‐10 source, and phenylboronic acid or RGD peptide as an active targeting moiety. Some hydroxy groups in PG were oxidized to carboxy groups (DND−PG−COOH) to conjugate the active targeting moiety. Some hydroxy groups in DND−PG−COOH were then transformed to azide to conjugate 10B12H112− through click chemistry. The nanodrugs were evaluated in vitro using B16 murine melanoma cells in terms of cell viability, BNCT efficacy and cellular uptake. As a result, the 10B12H112− moiety is found to facilitate cellular uptake probably due to its negative charge. Upon thermal neutron irradiation, the nanodrugs with 10B12H112− moiety exhibited good anticancer efficacies with slight differences with and without targeting moiety. [ABSTRACT FROM AUTHOR]

Extremely important aspects of the boron neutron capture therapy are, first of all, administering to the patient a boron compound that selectively reaches the neoplastic cells, and in the second step, the verification of the irradiation process. This paper focuses on the latter aspect, which is the detailed dosimetry of the processes occurring after the reaction of thermal neutrons with the boron-10 isotope. The results of computer simulations with the use of a new type of human head phantom filled with a polymer dosimetric gel will be presented in this article. [ABSTRACT FROM AUTHOR]

Boron has gained significant attention in medical research due to its B-10 isotope's high cross section for the reaction with thermal neutrons, generating ionizing particles that can eliminate cancer cells, propelling the development of boron neutron capture therapy (BNCT) for cancer treatment. The compound 4-borono-L-phenylalanine (BPA) has exhibited potential in BNCT clinical trials. Enhancing BPA uptake in cells involves proposing L-amino acid preloading. This study introduces a novel analytical strategy utilizing ICP-MS and single cell ICP-MS (SC-ICP-MS) to assess the effectiveness of L-tyrosine and L-phenylalanine preloading on human non-small cell lung carcinoma (A549) and normal Chinese hamster lung fibroblast (V79-4) models, an unexplored context. ICP-MS outcomes indicated that L-tyrosine and L-phenylalanine pre-treatment increased BPA uptake in V79-4 cells by 2.04 ± 0.74-fold (p = 0.000066) and 1.46 ± 0.06-fold (p = 0.000016), respectively. Conversely, A549 cells manifested heightened BPA uptake solely with L-tyrosine preloading, with a factor of 1.24 ± 0.47 (p = 0.028). BPA uptake remained higher in A549 compared to V79-4 regardless of preloading. SC-ICP-MS measurements showcased noteworthy boron content heterogeneity within A549 cells, signifying diverse responses to BPA exposure, including a subset with notably high BPA uptake. This study underscores SC-ICP-MS's utility in precise cellular boron quantification, validating cellular BPA uptake's heterogeneity. [ABSTRACT FROM AUTHOR]

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Boron neutron capture therapy (BNCT) is a cancer treatment option that combines preferential uptake of a boron compound in tumors and irradiation with thermal neutrons. For treatment planning, the boron concentration in different tissues must be considered. Neutron autoradiography using nuclear track detectors (NTD) can be applied to study both the concentration and microdistribution of boron in tissue samples. Histological sections are obtained from frozen tissue by cryosectioning. When the samples reach room temperature, they undergo an evaporation process, which leads to an increase in the boron concentration. To take this effect into account, certain correction factors (evaporation coefficients, CEv) must be applied. With this aim, a protocol was established to register and analyze mass variation of tissue sections, measured with a semimicro scale. Values of ambient temperature, pressure, and humidity were simultaneously recorded. Reproducible results of evaporation curves and CEv values were obtained for different tissue samples, which allowed the systematization of the procedure. This study could contribute to a more precise determination of boron concentration in tissue samples through the neutron autoradiography technique, which is of great relevance to make dosimetric calculations in BNCT. [ABSTRACT FROM AUTHOR]

Background: Boron neutron capture therapy (BNCT) is a binary radiotherapy based on the 10B(n, α)7Li capture reaction. Nonradioactive isotope 10B atoms which selectively concentrated in tumor cells will react with low energy neutrons (mainly thermal neutrons) to produce secondary particles with high linear energy transfer, thus depositing dose in tumor cells. In clinical practice, an appropriate treatment plan needs to be set on the basis of the treatment planning system (TPS). Existing BNCT TPSs usually use the Monte Carlo method to determine the three‐dimensional (3D) therapeutic dose distribution, which often requires a lot of calculation time due to the complexity of simulating neutron transportation. Purpose: A neural network‐based BNCT dose prediction method is proposed to achieve the rapid and accurate acquisition of BNCT 3D therapeutic dose distribution for patients with glioblastoma to solve the time‐consuming problem of BNCT dose calculation in clinic. Methods: The clinical data of 122 patients with glioblastoma are collected. Eighteen patients are used as a test set, and the rest are used as a training set. The 3D‐UNET is constructed through the design optimization of input and output data sets based on radiation field information and patient CT information to enable the prediction of 3D dose distribution of BNCT. Results: The average mean absolute error of the predicted and simulated equivalent doses of each organ are all less than 1 Gy. For the dose to 95% of the GTV volume (D95), the relative deviation between predicted and simulated results are all less than 2%. The average 2 mm/2% gamma index is 89.67%, and the average 3 mm/3% gamma index is 96.78%. The calculation takes about 6 h to simulate the 3D therapeutic dose distribution of a patient with glioblastoma by Monte Carlo method using Intel Xeon E5‐2699 v4, whereas the time required by the method proposed in this study is almost less than 1 s using a Titan‐V graphics card. Conclusions: This study proposes a 3D dose prediction method based on 3D‐UNET architecture in BNCT, and the feasibility of this method is demonstrated. Results indicate that the method can remarkably reduce the time required for calculation and ensure the accuracy of the predicted 3D therapeutic dose‐effect. This work is expected to promote the clinical development of BNCT in the future. [ABSTRACT FROM AUTHOR]

To treat superficial tumors using accelerator-based boron neutron capture therapy (ABBNCT), a technique was investigated, based on which, a single-neutron modulator was placed inside a collimator and was irradiated with thermal neutrons. In large tumors, the dose was reduced at their edges. The objective was to generate a uniform and therapeutic intensity dose distribution. In this study, we developed a method for optimizing the shape of the intensity modulator and irradiation time ratio to generate a uniform dose distribution to treat superficial tumors of various shapes. A computational tool was developed, which performed Monte Carlo simulations using 424 different source combinations. We determined the shape of the intensity modulator with the highest minimum tumor dose. The homogeneity index (HI), which evaluates uniformity, was also derived. To evaluate the efficacy of this method, the dose distribution of a tumor with a diameter of 100 mm and thickness of 10 mm was evaluated. Furthermore, irradiation experiments were conducted using an ABBNCT system. The thermal neutron flux distribution outcomes that have considerable impacts on the tumor's dose confirmed a good agreement between experiments and calculations. Moreover, the minimum tumor dose and HI improved by 20 and 36%, respectively, compared with the irradiation case wherein a single-neutron modulator was used. The proposed method improves the minimum tumor volume and uniformity. The results demonstrate the method's efficacy in ABBNCT for the treatment of superficial tumors. [ABSTRACT FROM AUTHOR]

Background: For boron neutron capture therapy (BNCT), the improvements in patient dosimetry will require information about the spatial variation of 10B concentration in the tumor and critical organs. A non-invasive approach, based on the detection of prompt gamma (PG) rays from the BNC reaction, may be well-suited to obtain such information. The detectability of the BNC PG rays has been shown experimentally utilizing energy-resolving cadmium telluride (CdTe) detectors. However, the feasibility of this approach under the clinically relevant conditions of BNCT is currently unknown. Purpose: The present work aimed to investigate the aforementioned feasibility by performing Monte Carlo (MC) simulations under the phantom irradiation geometry relevant to accelerator-based BNCT (a-BNCT). Especially, this investigation focused on demonstrating the enhanced detection of the BNC PG rays using a novel neutron shield for CdTe detectors. Upon demonstrating the efficacy of the proposed detector shield, the BNC PG ray-based quantitative imaging of clinically relevant concentrations of 10B was also demonstrated. Methods: The Geant4 MC simulation toolkit was used to model the phantom irradiation by an epithermal neutron beam as well as the detection of the BNC PG rays from the phantom by CdTe detectors with and without the proposed gadolinium (Gd)-based detector shield. It was also used to model the BNC PG ray-based quantitative imaging of 10B concentrations under a-BNCT scenarios. Each model included a 20 cm-diameter/24 cm-height cylindrical PMMA phantom containing 10B inserts at various concentrations. Arrays of CdTe crystals of 5 × 5 × 1 mm3 each (up to 120 in the case of a ring detector) were modeled for acquiring the BNC PG ray signals and quantitative imaging. Results: According to the MC simulations,thermalized neutrons from the phantom were found to reach the CdTe detector and captured by Cd and Te, resulting in the gamma ray background noise that directly interfered with the BNC PG ray signal. The proposed Gd-based detector shield was found to be highly effective in shielding thermal neutrons from the phantom,thereby reducing the unwanted gamma ray background noise. Owing to this shield, the detection of as low as seven parts-per-million (ppm) of 10B within the phantom of clinically relevant size was possible using 20 billion incident neutron histories. Furthermore, quantitative imaging of 10B distributed at low concentration (down to 50 ppm) within the phantom was demonstrated using computed tomography (CT) simulations with 16 billion incident neutron histories per angular projection. The 10B detection limit (7.5 ppm) was also estimated using the reconstructed CT image. Both 10B detection limits determined from this investigation are deemed clinically relevant for BNCT. Conclusions: The proposed Gd-based detector shield played an essential role for achieving the currently reported 10B detection limits. Overall, the present MC simulation work demonstrated highly sensitive BNC PG ray detection and imaging under a-BNCT scenarios using CdTe detectors coupled with a novel detector shield. [ABSTRACT FROM AUTHOR]

This study aims to develop poly lactic-co-glycolic acid (PLGA) nanoparticles with an innovative imaging-guided approach based on Boron Neutron Capture Therapy for the treatment of mesothelioma. The herein-reported results demonstrate that PLGA nanoparticles incorporating oligo-histidine chains and the dual Gd/B theranostic agent AT101 can successfully be exploited to deliver a therapeutic dose of boron to mesothelioma cells, significantly higher than in healthy mesothelial cells as assessed by ICP-MS and MRI. The selective release is pH responsive taking advantage of the slightly acidic pH of the tumour extracellular environment and triggered by the protonation of imidazole groups of histidine. After irradiation with thermal neutrons, tumoral and healthy cells survival and clonogenic ability were evaluated. Obtained results appear very promising, providing patients affected by this rare disease with an improved therapeutic option, exploiting PLGA nanoparticles. [ABSTRACT FROM AUTHOR]

• From 2010, KUR transitioned its operations from high-enrichment fuel to low-enrichment fuel. • The neutron energy spectrum of KUR-HWNIF has not been reevaluated with high accuracy since then. • The neutron energy spectrum of KUR-HWNIF was reevaluated using the multifoil activation method. • The reevaluated neutron absorption dose rate remained acceptable for BNCT biological viewpoint. The Heavy-Water Thermal Neutron Facility at Kyoto University Research Reactor (KUR) has been operational for boron neutron capture therapy (BNCT) since May 1974. Following a facility construction update in 1996, the facility name was changed to the Heavy-Water Neutron Irradiation Facility (HWNIF), and the neutron energy spectra were evaluated using the multifoil activation method. In May 2010, the KUR transitioned its operations from high-enrichment fuel to low-enrichment fuel. However, the neutron energy spectrum in the KUR-HWNIF has not been reevaluated with high accuracy since then. This paper reports the reevaluation of the neutron energy spectrum for the standard epithermal-neutron irradiation mode using the multifoil activation method. Based on the reevaluated results, the epithermal- and fast-neutron fluxes increased by approximately 34 % and 19 %, respectively. The neutron absorption dose rate at evaluation point was approximately 17 % lower than the previous one; however, it remained acceptable from the perspective of BNCT biological irradiation. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a radiotherapy technology that selectively kills tumor cells via the 10B(n, α)7Li reactions. Epithermal neutrons (0.5 eV–10 keV) are emitted and converted into thermal neutrons, which have a larger neutron capture reaction cross-section, by slowing down in the human body before reaching the tumor. Recently, the development of an epithermal neutron absolute flux intensity measurement technique has become crucial for real-time in-vivo dose monitoring in BNCT. In this study, a concept for a measurement system consisting of multiple compact scintillator with optical fibers detectors covered with neutron absorbers of various thicknesses is proposed. The designed system achieves a consistent response to epithermal neutrons with a theoretical coefficient of variation not higher than 5% for both LiCAF and EJ-254 scintillators. The theoretical feasibility of the proposed measurement system was investigated by an irradiation experiment carried out at the heavy water neutron irradiation facility at the Kyoto University Reactor. The experimental results indicated that further improvement and refinement are necessary to meet the high accuracy and precision required for real-time dose monitoring in clinical applications. • A scintillator-based compact system used for real-time neutron flux measurement. • Using multiple detectors covered by absorbers to modify the detector response. • Consistent response to epi-thermal neutrons from 0.5 eV to 10 keV. • Irradiation experiments using a therapeutic neutron beam. • Applications in real-time in-vivo dose monitoring for BNCT. [ABSTRACT FROM AUTHOR]

A prompt gamma neutron activation analysis (PGNAA) facility is being designed and developed at the channel 4 of the RA-3 nuclear reactor, placed at the Ezeiza Atomic Center of the National Atomic Energy Commission of Argentina. The main purpose of such facility is to perform fast measurements of 10 B concentration in biological samples, in the context of Boron Neutron Capture Therapy (BNCT). At this stage, a simulation guided design process has been performed for this facility. The MCNP6 code was used to perform computational simulations which have received the feedback from measurements of the implemented designs through an iterative process. The specifications of the required beam have been defined based on the sizes and types of biological samples and the lowest values of boron concentrations that would need to be measured for BNCT activities. The conformation of the neutron beam in terms of geometry and energy, has been achieved by the implementation of a system of collimators and filters. The goal of this development is to be able to measure micrograms of 10 B in a few minutes of irradiation. This measurement technique needs no preparation of the samples, is reliable, robust and safe. In order to satisfy these requirements, it is necessary to provide a high thermal neutron flux E < 0. 4 eV , ϕ th with low epithermal 0. 4 eV < E < 10 keV , ϕ epi and fast E > 10 keV , ϕ f components of the neutron flux, and also low gamma flux in the sample position and its surroundings. Based on the results of the simulations of the designs, the one that was considered the best design at this stage resulted in a ϕ th = (5. 6 ± 1. 4) × 1 0 7 n cm − 2 s − 1 with around four orders of magnitude less for higher energy components at sample position. The diameter of the beam with uniform ϕ th at the sample position was 3. 50 ± 0. 25 cm. The next design stage will include coupled transport of neutron and gamma particles. It will be focused in optimizing the gamma background at the detector position, which would allow to have a functional configuration of the complete measuring device. • A development of a prompt gamma facility for boron determination is on course. • Boron Neutron Capture Therapy applications are the main purpose of this facility. • The facility is located at channel 4 of the RA-3 nuclear reactor in Argentina. • Simulations with Monte Carlo particle transport guided the design process. • High neutron flux with low high energy components resulted at sample position. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a treatment in which tumor cells are irradiated with thermal neutrons after they have absorbed boron drug. The boron neutron capture reaction occurs in the cells that have taken up the boron drug and selectively destroys the cells, thereby maximizing the effect on the tumor cells while minimizing damage to normal tissue. Since June 2020, accelerator-based BNCT has been a healthcare service covered by health insurance in Japan to treat unresectable locally advanced or locally recurrent head and neck cancers. However, its role in the standard of treatment of surgery, radiation therapy, and chemotherapy is not yet clear. Therefore, we aimed to evaluate the clinical outcomes of BNCT as a health insurance treatment and explore its role among the standard treatment modalities for head and neck cancers. We retrospectively analyzed data of patients treated with BNCT at Kansai BNCT Medical Center, Osaka Medical and Pharmaceutical University, between June 2020 and May 2022. Post-treatment follow-up was performed at our institution whenever possible; however, if the patient lived too far away, it was performed at the referring institution. The observation period lasted until February 2024. We evaluated the best overall response rate according to the Response Evaluation Criteria in Solid Tumors version 1.1, and adverse events according to the Common Terminology Criteria for Adverse Events, version 5.0. In addition, we performed a survival analysis and examined the factors that contributed to the treatment outcomes. Sixty-nine patients (72 treatments) were included in the study, with a median observation follow-up of 17 months. The best overall response rate was 80.5%, and the 1-year locoregional control, progression-free survival, and overall survival rates were 57.6% (95% confidence interval [CI]: 44.4–68.7%), 42.8% (95% CI = 30.7–54.3%), and 76.0% (95% CI = 63.3–84.8%), respectively. There was a trend toward longer locoregional control in patients with earlier TNM staging. Regarding late adverse events (Grade 3 or higher), skin ulceration, pharyngeal fistula, central nervous system necrosis, esophageal perforation, and laryngeal necrosis were observed in 3 cases, 2 cases, 2 cases, 1 case, and 1 case, respectively. The case of esophageal perforation resulted in a grade 5 perforation due to carotid rupture. BNCT may be an effective treatment option for unresectable locally advanced or locally recurrent head and neck cancer with no other definitive therapies. When definitive surgery or radiation therapy are not feasible, BNCT may be considered in the early stages of the disease. Although the conditions of its indication should be carefully considered, the risk is considered acceptable given the tumor status and limited alternative treatment options. [ABSTRACT FROM AUTHOR]

The experimental radiation therapy involving thermal neutron capture by boron (boron neutron capture therapy, BNCT) offers the advantage of high-LET ions with ranges on the order of a cell nucleus. Efforts to implement it have encountered serious difficulties. A practical model system would be able to address the underlying mechanisms of DNA damage and also calibrate Monte Carlo simulations. We describe the characterization of a plasmid-based model in which DNA condensed with a tetra-arginine peptide is co-aggregated with mercapto-closo-dodecaborate (BSH) coated gold nanoparticles (AuNPs). Condensed DNA is an excellent model for cellular chromatin, and the AuNPs are able to function as boron carriers and neutron dosimeters. Data from light scattering, UV–visible spectroscopy, fluorescence spectroscopy, sedimentation behavior, gel electrophoresis, and atomic force microscopy all indicate that the basic peptide acts to co-aggregate the two polyanionic species DNA and BSH-coated AuNPs. This aggregation is easily reversed by an increase in ionic strength to free the plasmid for subsequent assay. We argue that this three-component system is simpler, more convenient, and more flexible than other models requiring covalent attachments between DNA, boron, and/or gold. • Model system for DNA damage by neutron capture on boron. • Condensed DNA aggregates reproduce the packing in chromatin and the size of cell nuclei. • Gold nanoparticles provide increased boron content over previous models. • Gold nanoparticles are suitable for neutron dosimetry. • DNA easily recoverable due to reversible electrostatic binding. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy is a low-invasive cancer therapy based on the neutron fission process that occurs upon thermal neutron irradiation of 10B-containing compounds; this process causes the release of alpha particles that selectively damage cancer cells. Although several clinical studies involving mercaptoundecahydro-closo-dodecaborate and the boronophenylalanine–fructose complex are currently ongoing, the success of this promising anticancer therapy is hampered by the lack of appropriate drug delivery systems to selectively carry therapeutic concentrations of boron atoms to cancer tissues, allowing prolonged boron retention therein and avoiding the damage of healthy tissues. To achieve these goals, numerous research groups have explored the possibility to formulate nanoparticulate systems for boron delivery. In this review. we report the newest developments on boron vehiculating drug delivery systems based on nanoparticles, distinguished on the basis of the type of carrier used, with a specific focus on the formulation aspects. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy is a unique treatment method that aims to kill the tumor cells with the help of heavy particles. Particles resulting from the interaction of the tumor region containing 10B atoms with thermal or epithermal neutrons have the most important role in this treatment method. In this study, gamma radiation reaching healthy tissues, which is the result of 10B (n,α )7Li reaction, was investigated. A simulation suitable for boron neutron capture therapy treatment, including the human head model, was created by the Monte Carlo N-Particle (MCNP) program. By using five different neutron energies, the gamma radiations resulting from the 10B(n,α )7 Li reaction in the determined regions, close to the tumor tissue, were investigated. It was observed that the healthy tissue between the tumor area and the surface is exposed to the highest gamma flux and the highest gamma radiation absorption. It was also observed that these values increase as neutron energy decreases. It was found that the gamma doses received by some regions outside the neutron irradiation area could be significant. It has been understood that the change in neutron energy may cause significant changes in gamma radiation values reaching healthy tissues, especially in regions close to the surface. In boron neutron capture therapy treatments, the neutrons sent to the tumor should be selected depending on the location of the tumor and the size of the tumor area. This study contains significant data about photon doses in healthy tissues around the brain region treated using different neutron energies with the boron neutron capture therapy technique. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a re-emerging technique for selectively killing tumor cells. Briefly, the mechanism can be described as follows: after the uptake of boron into cells, the thermal neutrons trigger the fission of the boron atoms, releasing the α-particles and recoiling lithium particles and high-energy photons that damage the cells. We performed a detailed study of the reactor dosimetry, cellular dose assessment, and radiobiological effects induced by BNCT in glioblastoma (GBM) cells. At maximum reactor power, neutron fluence rates were ϕ0 = 6.6 × 107 cm−2 s−1 (thermal) and θ = 2.4 × 104 cm−2 s−1 with a photon dose rate of 150 mGy·h−1. These values agreed with simulations to within 85% (thermal neutrons), 78% (epithermal neutrons), and 95% (photons), thereby validating the MCNPX model. The GEANT4 simulations, based on a realistic cell model and measured boron concentrations, showed that >95% of the dose in cells was due to the BNC reaction. Carboranylmethylbenzo[b]acridone (CMBA) is among the different proposed boron delivery agents that has shown promising properties due to its lower toxicity and important cellular uptake in U87 glioblastoma cells. In particular, the results obtained for CBMA reinforce radiobiological effects demonstrating that damage is mostly induced by the incorporated boron with negligible contribution from the culture medium and adjacent cells, evidencing extranuclear cell radiosensitivity. [ABSTRACT FROM AUTHOR]

Low energy accelerator driven neutron sources are promising candidates to obtain a neutron yield as high as 1014 n/s, which is required for a variety of applications, such as boron neutron capture therapy, neutron imaging, and neutron scattering. The methods to generate neutrons can be divided into two categories: hadron-based and photon-based methods. In order to better understand which kind of source would be the better choice for delivering a brilliant neutron beam robustly, in this paper, the underlying principles of neutron production, as well as the simulation results of neutron yield, target heat dissipation, thermal stress, and reaction byproducts concentration of these two types of neutron sources, will be elaborated on. A preliminary photoneutron target station design based on a 50 MeV/50 kW electron linear accelerator, including the optimized neutron yield, thermal hydraulic analysis, and shielding calculation, is presented as well to demonstrate the method to deliver brilliant thermal neutron beam of 1.03 × 1010 cm−2 s−1 sr−1. [ABSTRACT FROM AUTHOR]

The distribution of the thermal neutron flux has a significant impact on the treatment efficacy. We developed an irradiation method of overlapping irradiation fields using intensity modulators for the treatment of superficial tumors with the aim of expanding the indications for accelerator-based boron neutron capture therapy (BNCT). The shape of the intensity modulator was determined and Monte Carlo simulations were carried out to determine the uniformity of the resulting thermal neutron flux distribution. The intensity modulators were then fabricated and irradiation tests were conducted, which resulted in the formation of a uniform thermal neutron flux distribution. Finally, an evaluation of the tumor dose distribution showed that when two irradiation fields overlapped, the minimum tumor dose was 27.4 Gy-eq, which was higher than the tumor control dose of 20 Gy-eq. Furthermore, it was found that the uniformity of the treatment was improved 47% as compared to the treatment that uses a single irradiation field. This clearly demonstrates the effectiveness of this technique and the possibility of expanding the indications to superficially located tumors. [ABSTRACT FROM AUTHOR]

Objective: Glioblastoma (WHO classification Grade IV) is a highly malignant brain tumor with a high propensity for recurrence even after standard treatments. Patient death is inevitable, as the available methods are largely ineffective for remediation and treatment once recurrence has occurred. This review presents recent advancements in boron neutron capture therapy (BNCT) that have allowed for its clinical use in treating glioblastoma. Data Sources: We retrospectively reviewed the results of clinical trials and articles published in the past 30 years worldwide. Study Selection: All included studies addressed the use of BNCT to treat high-grade gliomas, including glioblastoma. Results: The development of boron-containing agents exhibiting specificity and improvements in technologies that generate neutron sources have led to the clinical use of BNCT for treating tumors. BNCT involves the delivery of a boron-10-containing drug specifically to tumor cells, followed by irradiation with low-energy thermal neutrons to generate two biologically active particles (helium [α particle] and lithium nuclei). Although these particles are highly effective at destroying cells, their field of destruction is limited to the tumor cells. Therefore, BNCT serves as an excellent mode of targeted particle therapy for tumors, particularly those that are infiltrative. The published articles reviewed here demonstrate the gradual refinement of the BNCT technique and prolonged survival for glioma patients compared to conventional treatments. Conclusion: With continued improvements, BNCT may become the first-choice treatment for malignant infiltrative glioblastoma in the near future. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to design and evaluate a neutron filtration system to improve the dose distribution of an accelerator‐based neutron capture therapy system. Methods: An LiF‐sintered plate composed of 99%‐enriched 6Li was utilized to filter out low‐energy neutrons to increase the average neutron energy at the beam exit. A 5‐mm thick filter to fit inside a 12‐cm diameter circular collimator was manufactured, and experimental measurements were performed to measure the thermal neutron flux and gamma‐ray dose rate inside a water phantom. The experimental measurements were compared with the Monte Carlo simulation, particle, and heavy ion transport code system. Following the experimental verification, three filter designs were modeled, and the thermal neutron flux and the biologically weighted dose distribution inside a phantom were simulated. Following the phantom simulation, a dummy patient CT dataset was used to simulate a boron neutron capture therapy (BNCT) irradiation of the brain. A mock tumor located at 4, 6, 8 cm along the central axis and 4‐cm off‐axis was set, and the dose distribution was simulated for a maximum total biologically weighted brain dose of 12.5 Gy with a beam entering from the vertex. Results: All three filters improved the beam penetration of the accelerator‐based neutron source. Filter design C was found to be the most suitable filter, increasing the advantage depth from 9.1 to 9.9 cm. Compared with the unfiltered beam, the mean weighted dose in the tumor located at a depth of 8 cm along the beam axis was increased by ∼25%, and 34% for the tumor located at a depth of 8 cm and off‐axis by 4 cm. Conclusion: A neutron filtration system for an accelerator‐based BNCT system was investigated using Monte Carlo simulation. The proposed filter design significantly improved the dose distribution for the treatment of deep targets in the brain. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a binary modality that is used to treat a variety of malignancies, using neutrons to irradiate boron-10 (10B) nuclei that have entered tumor cells to produce highly linear energy transfer (LET) alpha particles and recoil 7Li nuclei (10B [n, α] 7Li). Therefore, the most important part in BNCT is to selectively deliver a large number of 10B to tumor cells and only a small amount to normal tissue. So far, BNCT has been used in more than 2000 cases worldwide, and the efficacy of BNCT in the treatment of head and neck cancer, malignant meningioma, melanoma and hepatocellular carcinoma has been confirmed. We collected and collated clinical studies of second-generation boron delivery agents. The combination of different drugs, the mode of administration, and the combination of multiple treatments have an important impact on patient survival. We summarized the critical issues that must be addressed, with the hope that the next generation of boron delivery agents will overcome these challenges. [ABSTRACT FROM AUTHOR]

In boron neutron capture therapy (BNCT), neutrons and γ-rays cause different biological effects, and it is necessary to discriminate between them for treatment planning and periodic inspections. Currently, the BeO powder thermoluminescence dosimeter (BeO powder TLD) is used for γ-ray dosimetry in mixed neutron and γ-ray fields due to the small capture cross section for neutrons, but correction is required because of the effects of neutron-induced activation. Besides, sales of BeO powder TLDs have been discontinued because the highly toxic BeO is readily dispersed when the detector is damaged. Therefore, the development of alternative replacement technologies for BeO powder TLDs that are not affected by neutrons is an important issue. In this study, we investigated the measurement of the γ-ray dose during BNCT using a BeO ceramic TLD, whereby the BeO was not released into the air. After 5, 15, 30, and 60 min of irradiation using the Kyoto University Research Reactor, the amount of thermoluminescence (TL) from the BeO ceramic TLD was shown to increase with irradiation time. In addition, the γ-ray dose, which was derived by converting the amount of TL to the dose, showed excellent proportionality to the irradiation time and was found to be comparable to the γ-ray dose measured with a BeO powder TLD. These results demonstrated that the BeO ceramic TLD can selectively measure only the γ-ray dose without influence by neutrons. Thus, our approach represents a new γ-ray dose measurement strategy that does not require correction for the contribution from thermal neutrons. [ABSTRACT FROM AUTHOR]

While boron neutron capture therapy (BNCT) depends primarily on the short flight range of the alpha particles emitted by the boron neutron capture reaction, gadolinium neutron capture therapy (GdNCT) mainly relies on gamma rays and Auger electrons released by the gadolinium neutron capture reaction. BNCT and GdNCT can be complementary in tumor therapy. Here, we studied the combined effects of BNCT and GdNCT when boron and gadolinium compounds were co-injected, followed by thermal neutron irradiation, and compared these effects with those of the single therapies. In cytotoxicity studies, some additive effects (32‒43%) were observed when CT26 cells were treated with both boron- and gadolinium-encapsulated PEGylated liposomes (B- and Gd-liposomes) compared to the single treatments. The tumor-suppressive effect was greater when BNCT was followed by GdNCT at an interval of 10 days rather than vice versa. However, tumor suppression with co-injection of B- and Gd-liposomes into tumor-bearing mice followed by neutron beam irradiation was comparable to that observed with Gd-liposome-only treatment but lower than B-liposome-only injection. No additive effect was observed with the combination of BNCT and GdNCT, which could be due to the shielding effect of gadolinium against thermal neutrons because of its overwhelmingly large thermal neutron cross section. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy is based on a nuclear reaction between the nonradioactive isotope boron‐10 and either low‐energy thermal neutrons or high‐energy epithermal neutrons, which generate high linear energy transfer α particles and a recoiled lithium nucleus (7Li) that selectively destroys the DNA helix in tumor cells. Boron neutron capture therapy is an emerging procedure aimed at improving the therapeutic ratio for the traditional treatment of various malignancies, which has been studied clinically in a variety of diseases, including glioblastoma, head and neck cancer, cutaneous melanoma, hepatocellular carcinoma, lung cancer, and extramammary Paget's disease. However, boron neutron capture therapy has not been clinically performed for urological cancers, excluding genital extramammary Paget's disease that appeared at the scrotum to penis area. In this review, we aimed to provide an updated summary of the current clinical literature of patients treated with boron neutron capture therapy and to focus on the future prospects of boron neutron capture therapy for urological cancers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A LiF-Si-based active neutron detector was developed for the measurement of real-time BNCT neutron beam. Thermal-neutron detection efficiencies were adjustable to the neutron beam intensities at various measurement locations by simply exchanging the LiF neutron converter, while minimizing sensitivity to photons. The neutron detection efficiency ranges from 8 × 10−7 to 8 × 10−4 cm2. The thermal-neutron detection efficiencies were experimentally obtained by placing the neutron detectors inside an education reactor. Experimental results were verified using a Monte Carlo simulation technique. The simulated thermal-neutron detection efficiencies were in good agreement with the experimental results within the range of experimental uncertainties. Discrepancies in both sets of results were due to an insufficient assessment of LiF density and flatness. Surface-density neutron detection efficiencies were proposed to more accurately measure neutron fluence rates. • LiF-Si-based active neutron detector was developed for measurement of BNCT beam. • Thermal-neutron detection efficiencies were experimentally obtained at UTR-KINKI. • Experimental results were verified using a Monte Carlo simulation technique. • Thermal-neutron detection efficiency can be tailored to neutron beam intensity. • The neutron detection efficiency ranges from 8 × 10−7 to 8 × 10−4 cm2. [ABSTRACT FROM AUTHOR]

Sufficient boron-10 isotope (10B) accumulation by tumor cells is one of the main requirements for successful boron neutron capture therapy (BNCT). The inability of the clinically registered 10B-containing borophenylalanine (BPA) to maintain a high boron tumor concentration during neutron irradiation after a single injection has been partially solved by its continuous infusion; however, its lack of persistence has driven the development of new compounds that overcome the imperfections of BPA. We propose using elemental boron nanoparticles (eBNPs) synthesized by cascade ultrasonic dispersion and destruction of elemental boron microparticles and stabilized with hydroxyethylcellulose (HEC) as a core component of a novel boron drug for BNCT. These HEC particles are stable in aqueous media and show no apparent influence on U251, U87, and T98G human glioma cell proliferation without neutron beam irradiation. In BNCT experiments, cells incubated with eBNPs or BPA at an equivalent concentration of 40 µg 10B/mL for 24 h or control cells without boron were irradiated at an accelerator-based neutron source with a total fluence of thermal and epithermal neutrons of 2.685, 5.370, or 8.055 × 1012/cm2. The eBNPs significantly reduced colony-forming capacity in all studied cells during BNCT compared to BPA, verified by cell-survival curves fit to the linear-quadratic model and calculated radiobiological parameters, though the effect of both compounds differed depending on the cell line. The results of our study warrant further tumor targeting-oriented modifications of synthesized nanoparticles and subsequent in vivo BNCT experiments. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a re-emerging therapy with the ability to selectively kill tumor cells. After the boron delivery agents enter the tumor tissue and enrich the tumor cells, the thermal neutrons trigger the fission of the boron atoms, leading to the release of boron atoms and then leading to the release of the α particles (4He) and recoil lithium particles (7Li), along with the production of large amounts of energy in the narrow region. With the advantages of targeted therapy and low toxicity, BNCT has become a unique method in the field of radiotherapy. Since the beginning of the last century, BNCT has been emerging worldwide and gradually developed into a technology for the treatment of glioblastoma multiforme, head and neck cancer, malignant melanoma, and other cancers. At present, how to develop and innovate more efficient boron delivery agents and establish a more accurate boron-dose measurement system have become the problem faced by the development of BNCT. We discuss the use of boron delivery agents over the past several decades and the corresponding clinical trials and preclinical outcomes. Furthermore, the discussion brings recommendations on the future of boron delivery agents and this therapy. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is considered to have potential for cancer therapy based on the nuclear reaction between boron (10B) atoms and thermal neutrons, yielding 4He2+ (α) and 7Li3+ ions. These heavy particles induce the destruction of biomolecules within short path length of 5–9 μm, resulting in a limited cytotoxic effect to 10B‐containing cells. Herein, we report on the design and synthesis of DNA‐targeting BNCT agents equipped with homo‐ and hetero‐dimeric macrocyclic polyamine units and their Zn2+ complexes. It was hypothesized that the dizinc(II) complexes of these ligands would recognize two adjacent thymidines (thymidyl(3'–5')thymidine), resulting in an efficient contact with DNA and an efficient breakdown of DNA upon thermal neutron irradiation. To test this hypothesis, we performed a DNA interaction study and a biological evaluation such as cytotoxicity and intracellular uptake activity using cancer and normal cells. BNCT experiments utilizing the corresponding 10B‐enriched compounds were also conducted. [ABSTRACT FROM AUTHOR]

Purpose: To conduct research related to slow neutrons, fast neutrons must be mode‐rated and shifted to the desired energy region. Methods: In this research, an iterated prediction method, in which the neutron transportation properties of all materials were characterized by a reflection matrix, R, and a transmission matrix, T, was proposed to bypass a time‐consuming Monte Carlo simulation and predict the performance of the moderator, including the epithermal neutron flux and the dose of fast neutrons and gamma rays, used for boron neutron capture therapy (BNCT). To find the optimal solution in the huge parameter space, a genetic algorithm combined with transmission and reflection matrices was utilized. Results: The results showed that a 70‐loop iteration was able to find a design for the moderator of BNCT with almost 80% higher epithermal neutron flux per kilowatt than that of the empirically optimized moderator that was previously reported in the literature. Compared with the Monte Carlo method, this method had the advantage of reducing the calculation time and statistical errors. Conclusion: The genetic algorithm with matrices (GAM) method can be used to find an optimal solution in a huge parameter space without brute‐force calculations. It could be a promising method for designing the moderator for thermal or epithermal neutron usages. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is based on the nuclear reaction, such that B-10 irradiated with lowenergy thermal neutrons produces alpha particles with high linear energy transfer and lithium-7. Clinically, BNCT is used primarily for treatment of high-grade glioma or brain metastases from melanoma and, more recently, head, neck and liver cancers. Since reactors have long been used to produce high intensity neutron beams, nuclear reactors have also been used to produce BNCT. Accelerators can also be used to generate quasi-thermal neutrons, but none of them are currently used for BNCT. Boron medications with low molecular weight used in clinic include sodium borocaptate (BSH) and a phenylalanine derivative called boronophenyl alanine (BPA). The main challenge in the development of boron tracers is the selective targeting to reach a sufficient concentration of boron (F 20 Ag / g tumor) so that the tumor receives a sufficient dose of radiation and normal tissues receive minimal radiation. Clinical trials of BNCT are being conducted or have been conducted in various countries. Most patients undergoing BNCT were patients with high-grade brain tumors. The patients underwent surgery for complete or partial removal of the tumor and then received BNCT at various time intervals after surgery. BNCT in combination with other treatments such as surgery, chemotherapy and external beam radiotherapy can also be used as an adjuvant therapy for treatment of other tumors. This concomitant use may lead to improvements in patient survival. According to clinical studies, BNCT is a targeted therapy with promising results and acceptable toxicity. Important issues in this treatment include the need for more selective and effective agents for boron delivery carriers, development of methods for estimating semi-quantitative amounts of boron content in the tumor before treatment, clinical progress of BNCT and the need for randomized clinical trials with known therapeutic efficacy. If these issues are addressed enough, BNCT can develop as a treatment method. Further research is needed to determine the role of BNCT in clinical medicine. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) was first proposed as early as 1936, and research on BNCT has progressed relatively slowly but steadily. BNCT is a potentially useful tool for cancer treatment that selectively damages cancer cells while sparing normal tissue. BNCT is based on the nuclear reaction that occurs when 10B capture low-energy thermal neutrons to yield high-linear energy transfer (LET) α particles and recoiling 7Li nuclei. A large number of 10B atoms have to be localized within the tumor cells for BNCT to be effective, and an adequate number of thermal neutrons need to be absorbed by the 10B atoms to generate lethal 10B (n, α)7Li reactions. Effective boron neutron capture therapy cannot be achieved without appropriate boron carriers. Improvement in boron delivery and the development of the best dosing paradigms for both boronophenylalanine (BPA) and sodium borocaptate (BSH) are of major importance, yet these still have not been optimized. Here, we present a review of this treatment modality from the perspectives of radiation oncology, biology, and physics. This manuscript provides a brief introduction of the mechanism of cancer-cell-selective killing by BNCT, radiobiological factors, and progress in the development of boron carriers and neutron sources as well as the results of clinical study. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy is based on neutron capture by 10B and creation of high energy alpha particle and recoiled 7Li ion which have ranges comparable to cell dimensions. The MCNP5/X code is applied for calculation of the absorbed doses as well as dose distribution by depth in pancreas cancer and the organs of the analytical and voxelized Oak Ridge National Laboratory phantom, which represents the human body The depth dose distributions for thermal, epithermal neutrons, and neutron spectrum, show that the absorbed doses are the largest exactly in the cancer, in ah cases. It is found by this simulation that the epithermal neutrons are the optimal choice for BNC therapy. They deliver a similar dose to cancer as the thermal neutrons but, spare the healthy tissue more than the thermal ones. [ABSTRACT FROM AUTHOR]

In the neutron irradiation field in boron neutron capture therapy, neutron rays and γ-rays are mixed, and it is not easy to selectively measure only neutron rays. The currently used gold activation method is expensive and not suitable for measuring the dose distribution with high spatial resolution. Therefore, there is increasing demand for a simple neutron measurement method for periodic inspections and treatment planning in boron neutron capture therapy (BNCT). Cd has a large nuclear reaction cross section solely for thermal neutrons, and converts thermal neutrons to γ-rays by the (n, γ) reaction. Therefore, in this study, we investigated a method for calculating the thermal neutron fluence by installing Cd as a neutron converter on Cr-doped Al2O3 (Al2O3:Cr), which is a thermoluminescence dosimeter, and measuring the converted γ-ray dose with the Al2O3:Cr. After a 30 min irradiation experiment using the Kyoto University research reactor, the amount of thermoluminescence (TL) increased 101-fold after installing a Cd converter compared with the case of no Cd converter. In addition, the dependence of the TL response on the irradiation time showed excellent proportionality, suggesting the possibility of selectively measuring only the thermal neutron fluence. [ABSTRACT FROM AUTHOR]