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This study presents the successful synthesis of two perylenediimide (PDI)-based ortho-carborane (o-carborane) derivatives, PDI–CB1 and PDI–CB2, through the insertion of decaborane into alkyne-terminated PDIs (PDI1 and PDI2). The introduction of o-carborane groups did not alter the optical properties of the PDI units in solution compared to their carborane-free counterparts, maintaining excellent fluorescence quantum yields of around 100% in various solvents. This was achieved by using a methylene linker to minimize electronic interaction between PDI and o-carborane, and by incorporating bulky o-carborane groups at imide- position to enhance solubility and prevent π–π stacking-induced aggregation. Aggregation studies demonstrated that PDI–CB1 and PDI–CB2 have greater solubility than PDI1 and PDI2 in both nonpolar and aqueous solvents. Despite the steric hindrance imparted by the o-carborane units, the solid state emission of PDI–CB1 and PDI–CB2 was affected by aggregation-caused fluorescence quenching. However, solid PDI–CB1 preserved bright red excimer-type emission, which persisted in water-dispersible nanoparticles, indicating potential for application as a theranostic agent combining fluorescence bioimaging with anticancer boron neutron capture therapy (BNCT) due to its high boron content. [ABSTRACT FROM AUTHOR]

Icosahedral boron clusters-based BODIPY dyes represent a cutting-edge class of compounds that merge the unique properties of boron clusters with the exceptional fluorescence characteristics of BODIPY dyes. These kinds of molecules have garnered substantial interest due to their potential applications across various fields, mainly including optoelectronics, bioimaging, and potential use as boron carriers for Boron Neutron Capture Therapy (BNCT). Carborane clusters are known for their exceptional stability, rigid geometry, and 3D-aromaticity, while BODIPY dyes are renowned for their strong absorption, high fluorescence quantum yields, and photostability. The integration of carborane into BODIPY structures leverages the stability and versatility of carboranes while enhancing the photophysical properties of BODIPY-based fluorophores. This review explores the synthesis and structural diversity of boron clusters-based BODIPY dyes, highlighting how carborane incorporation can lead to significant changes in the electronic and optical properties of the dyes. We discuss the enhanced photophysical characteristics, such as red-shifted absorption and emission poperties, charge and electronic transfer effects, and improved cellular uptake, resulting from carborane substitution. The review also delves into the diverse applications of these compounds. In bioimaging, carborane-BODIPY dyes offer superior fluorescence properties and cellular internalization, making them ideal for cell tracking. In photodynamic therapy, (PDT) these dyes can act as potent photosensitizers capable of generating reactive oxygen species (ROS) for targeted cancer treatment making them excellent candidates for PDT. Additionally, their unique electronic properties make them suitable candidates for optoelectronic applications, including organic light-emitting diodes (OLEDs) and sensors. Overall, carborane-BODIPY dyes represent a versatile and promising class of materials with significant potential for innovation in scientific and technological applications. This review aims to provide a comprehensive overview of the current state of research on carborane-BODIPY dyes, highlighting their synthesis, properties, and broad application spectrum. [ABSTRACT FROM AUTHOR]

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]

Recurrent head and neck cancer presents a therapeutic challenge because of cumulative toxicity from initial radiation therapy, limiting reirradiation options. Boron neutron capture therapy (BNCT) offers a promising alternative, selectively delivering a radical dose to tumors while sparing adjacent normal tissue. This study investigates the initial clinical outcomes and prognostic factors associated with BNCT for recurrent squamous cell carcinoma of the head and neck. This retrospective analysis investigated the initial 47 patients treated with BNCT between May 2020 and February 2021 in Japan. All patients had received radiation therapy with a median dose of 70 Gy (range, 44-176) before BNCT. Median tumor size was 11 cm3 (range, 1-117 cm3), with 23% of tumors larger than 30 cm3, and 87% of patients had prior systemic therapy. The most common prescribed dose to the pharyngeal mucosa was 15 Gy-Eq (36%), followed by 18 Gy-Eq (34%). The minimum dose given to tumor was 27.4 Gy-Eq (range, 13.3-45.2). In 23 patients, 18F-fluoro-borono-phenylalanine positron emission tomography was performed within 1 week before BNCT, and the tumor-to-blood 10B ratio was 3.5 (range, 2.0-8.7). Efficacy analysis revealed a 51% complete response rate and a 74% overall response rate. Disease-free survival rates at 1 and 2 years were 34.6% and 26.6%, respectively. Overall survival rates at 1 and 2 years were 86.1% and 66.5%, respectively. Multivariate analysis revealed that, among the patient characteristics, whether the lesion was mucosal had a significant effect on achieving complete response. This study provided valuable insights into the early integration of BNCT into routine clinical practice, highlighting its efficacy and safety. Technical improvements are needed to ensure precise dose administration. Ongoing prospective studies, such as the phase II REBIVAL study, will further elucidate the role of BNCT in recurrent head and neck cancer. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) as a binary targeted particle radiotherapy strategy has shown potent anti‐cancer potential. However, biological barriers and restricted blood supply pose challenges in achieving adequate boron concentration within deep‐seated tumor lesions. BNCT with other anti‐cancer therapies, such as X‐ray radiotherapy and photothermal therapy, is devised to address the limitations of BNCT efficiency. However, the potential risk of organ‐accumulating toxicity and treatment complexity of dual exogenous activation hinders its development. To address this problem, newly redox‐responsive boron nano‐chains (RBNC) are reported that combine BNCT and endogenous chemodynamic therapy (CDT)‐enhanced ferroptosis. RBNC specifically activates nanoparticle size conversion (large‐to‐small) in response to GSH/H2O2 in the tumor microenvironment, releasing boron delivery agents boron quantum dots (BQD) and Fe3+. RBNC exhibits negligible systemic toxicity while demonstrating high boron accumulation at tumor. Meanwhile, the introduction of Fe3+ not only produces ·OH through reaction with H2O2, but also depletes GSH and reduces GPX4 activity in tumors, resulting in amplified intracellular oxidative stress and chemodynamically enhanced ferroptosis. Thus, the work provides a strategy to solve the problem of insufficient boron concentration and poor targeting of boron delivery agents and fill the gaps of BNCT combined with CDT and ferroptosis. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Boron neutron capture therapy (BNCT) is a next‐generation radiotherapy, utilizing both an external neutron beam and a 10B$^{10}{\rm B}$‐containing pharmaceutical. A compact accelerator for a high intensity neutron source was installed to conduct BNCT in a hospital. The dose administered to a patient was evaluated by measuring the proton beam current.Neutron intensity should be monitored in real‐time by measuring the neutrons emitted from the target during BNCT irradiation. This is crucial due to potential neutron target degradation. Online neutron beam monitoring systems are required for reliable measurements of the administered neutron dose. An online neutron beam monitoring system was developed to monitor neutron intensity irradiating on the patient at the National Cancer Center Hospital (NCCH).The neutron detector comprised a back‐illuminated thin Si diode of 40‐μm$\umu{\rm m}$ thickness and an ultrathin natural LiF neutron converter of 0.05‐μm$\umu{\rm m}$ thickness. The neutron detector was installed on the neutron target unit, regardless of whether a patient was present, without any additional modifications to the setup. The response functions for high photon dose rates of upto 100 Gy/h were measured. The pulse heights were measured using the neutron beam monitor during BNCT neutron irradiation. Neutron temporal response measured using the online beam monitor was acquired and compared with the proton beam current and the measurements at a patient position. From this measurement at the patient position, the neutron fluence rate irradiating on a patient was obtained.The neutron events were separated from the photon events. The neutron counting rates increased rapidly with the starting of proton beam irradiation and dropped to zero upon its termination. During intermittent drops and recoveries in the proton beam, the neutron beam monitor for counting rates responded quickly, synchronizing with the beam current. A scatter plot of the neutron counting rate and proton beam current indicated a good linear correlation. A direct relationship between the online neutron beam monitor's neutron counting rates and those of the patient neutron detector showed a good correlation coefficient of 0.84. A ratio of the both neutron counting rates showed a standard deviation of 6%. The correlation coefficient and standard deviation were improved to 0.94 and 1.5%, by re‐binning the neutron temporal response with longer acquisition period than 1 s. Using the online neutron beam monitor, the neutron fluence rate was obtained from the direct relationship within 1.5%. Therefore, real‐time monitoring of neutron intensity was achieved within the acceptable level as per the International Commission on Radiation Units and Measurements report.The online neutron beam monitoring system was developed to monitor the BNCT neutron beam intensity at NCCH. The temporal response of the neutron beam monitor was synchronized with the neutron counting rate at the patient position. Using the online neutron beam monitor, the neutron fluence rate irradiating on the patient can be monitored from the direct relationship. Fluctuation of the neutron beam intensity through BNCT irradiation and the degradation of the lithium target through the lifespan of the neutron target could be monitored using the neutron beam monitor. [ABSTRACT FROM AUTHOR]

Featured Application: This research presents a novel image reconstruction method for Boron Neutron Capture Therapy (BNCT)-Single Photon Emission Computed Tomography (SPECT) using Bayesian estimation with limited view-angle projection data. The method aims to address the inherent challenges in BNCT-SPECT imaging where conventional algorithms struggle with incomplete data from restricted projection angles. By improving the image accuracy under such conditions, this technique has potential applications in clinical settings, where accurate tumor localization and dose distribution are critical for the success of BNCT treatments. This method could lead to enhanced treatment planning and monitoring, ultimately improving patient outcomes. Boron Neutron Capture Therapy (BNCT) is an emerging radiation treatment for cancer, and its challenges are being explored. Systems capable of capturing real-time observations of this treatment's effectiveness, particularly BNCT-SPECT methods that measure gamma rays emitted instantaneously from outside the body during nuclear reactions and that reconstruct images using Single Photon Emission Computed Tomography (SPECT) techniques, remain unavailable. BNCT-SPECT development is hindered by two main factors, the first being the projection angle. Unlike conventional SPECT, the projection angle range which is achievable by rotating a detector array cannot exceed approximately 90 degrees. Consequently, Fourier-based image reconstruction methods, requiring projections from at least 180 degrees, do not apply to BNCT-SPECT. The second limitation is the measurement time. Given these challenges, we developed a new sequential approximation image reconstruction method using Bayesian estimation, which is effective under the stringent BNCT-SPECT conditions. We also compared the proposed method with the existing Maximum Likelihood-Expectation Maximization (ML-EM) image reconstruction method. Numerical experiments were conducted by obtaining BNCT-SPECT projection data from true images and reconstructing images using both the proposed and ML-EM methods from the resulting sinograms. Performance comparisons were conducted using a dedicated program applying Bayesian estimation and this showed promise as a new image reconstruction method useful under BNCT-SPECT conditions. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Boron neutron capture therapy (BNCT) is a targeted radiotherapy that relies on the 10B (n, α) 7Li reaction, which produces secondary particles with high linear energy transfer (LET), leading to a high relative biological effectiveness (RBE) in tumors. The biological effectiveness of BNCT is influenced by factors such as boron distribution and concentration, necessitating improved methods for assessing its radiobiological effects and clarifying the sensitivity of the differences in different factors to the biological effects.This paper introduces a method to evaluate the biological effects of BNCT using the cellular repair model. This method aims to overcome some of the limitations of current evaluation approaches. The primary goal is to provide guidance for clinical treatments and the development of boron drugs, as well as to investigate the impact of the synergistic effects of mixed radiation fields in BNCT on treatment outcomes.The approach involves three key steps: first, extending the radial energy deposition distribution of BNCT secondary particles using Geant4‐DNA. This allows for the calculation of initial DNA double‐strand breaks (DSBs) distributions for a given absorbed dose. Next, the obtained initial DSB distributions are used for DNA damage repair simulations to generate cell survival curves, then thereby quantifying RBE and compound biological effectiveness (CBE). The study also explores the synergistic effects of the mixed radiation fields in BNCT on assessing biological effects were also explored in depth.The results showed that the RBE of boronophenylalanine (BPA) and sodium borocaptate (BSH) drugs at cell survival fraction 0.01 was 2.50 and 2.15, respectively. The CBE of the boron dose component was 3.60 and 0.73, respectively, and the RBE of the proton component was 3.21, demonstrating that BPA has a significantly higher biological impact than BSH due to superior cellular permeability. The proton dose significance in BNCT treatment is also underscored, necessitating consideration in both experimental and clinical contexts. The study demonstrates that synergistic effects between disparate radiation fields lead to increased misrepairs and enhanced biological impact. Additionally, the biological effect diminishes with rising boron concentration, emphasizing the need to account for intercellular DNA damage heterogeneity.This methodology offers valuable insights for the development of new boron compounds and precise assessment of bio‐weighted doses in clinical settings and can be adapted to other therapeutic modalities. [ABSTRACT FROM AUTHOR]

Recent advances in luminescent materials highlight the significant impact of hydrogen isotope effects on improving optoelectronic properties. However, the research on the influence of the boron isotope effects on photophysical properties remains underdeveloped. This study focused on exploring the boron isotope effects in boron‐cluster‐based luminogens. In doing so, we designed and synthesized carborane‐based luminogens containing 98 % 10B and 95 % 11B, respectively, and observed distinct photophysical behaviors. Compared to the 10B‐enriched luminogens, the 11B‐enriched counterparts can significantly enhance luminescence efficiency, prolong emission lifetime, and reduce full‐width at half‐maximum. Additionally, increased thermal stability, redshifted B−H vibrations, and a fourfold enhanced electrochemiluminescence intensity have also been observed. On the other hand, the biological assessments of a 10B‐enriched luminogen reveals low cytotoxicity, high boron uptake, and excellent fluorescence imaging capability, indicating the potential application in boron neutron capture therapy (BNCT). This work presents the first comprehensive exploration on the boron isotope effects in boron clusters, and provides valuable insights into the rational design of organic luminogens for advanced optoelectronic and biomedical applications. [ABSTRACT FROM AUTHOR]

Background: Boron neutron capture therapy (BNCT) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Based on previous studies in tumor-bearing mice, this study evaluated the biodistribution of the sodium salt of cobaltabis(dicarbollide) (Na[3,3′-Co(C2B9H11)2], abbreviated as Na[o-COSAN]) in the hamster cheek pouch oral cancer model and the Na[o-COSAN]/BNCT therapeutic effect on tumors and induced radiotoxicity. The synthesis and comprehensive characterization of 10B-enriched trimethylammonium salt of nido-[7,8-C210B9H12]−o-carborane, along with the cesium and sodium salts of [o-10COSAN] cobaltabis(dicarbollide) are reported here for the first time. Methods: Hamsters bearing tumors were injected with Na[o-COSAN] (7.5 mg B/kg) and euthanized at different time-points after injection (30 min, 2, 3, 5, and 18 h post-administration) to evaluate boron uptake in different tissues/organs. Based on these results, tumor-bearing animals were treated with Na[10B-o-COSAN]/BNCT (7.5 mg B/kg b.w., 3 h), prescribing 5 Gy total in absorbed dose to the precancerous tissue surrounding tumors, i.e., the dose-limiting tissue. Results: Na[o-10COSAN] exhibited no toxicity. Although biodistribution studies employing Na[o-COSAN] have shown low absolute boron concentration in the tumor (approx. 11 ppm), Na[o-10COSAN]/BNCT induced a high and significant therapeutic effect on tumors versus the control group (cancerized, untreated animals). Moreover, only half of the animals exhibited severe mucositis in the precancerous dose-limiting tissue after BNCT, which resolved completely at 21 days after irradiation. Conclusions: Na[o-10COSAN] would be potentially useful to treat head and neck cancer with BNCT. [ABSTRACT FROM AUTHOR]

In recent years, various drug delivery systems circumventing the blood–brain barrier have emerged for treating brain tumors. This study aimed to improve the efficacy of brain tumor treatment in boron neutron capture therapy (BNCT) using cerebrospinal fluid (CSF) circulation to deliver boronophenylalanine (BPA) to targeted tumors. Previous experiments have demonstrated that boron accumulation in the brain cells of normal rats remains comparable to that after intravenous (IV) administration, despite BPA being administered via CSF at significantly lower doses (approximately 1/90 of IV doses). Based on these findings, BNCT was conducted on glioma model rats at the Kyoto University Research Reactor Institute (KUR), with BPA administered via CSF. This method involved implanting C6 cells into the brains of 8-week-old Wistar rats, followed by administering BPA and neutron irradiation after a 10-day period. In this study, the rats were divided into four groups: one receiving CSF administration, another receiving IV administration, and two control groups without BPA administration, with one subjected to neutron irradiation and the other not. In the CSF administration group, BPA was infused from the cisterna magna at 8 mg/kg/h for 2 h, while in the IV administration group, BPA was intravenously administered at 350 mg/kg via the tail vein over 1.5 h. Thermal neutron irradiation (5 MW) for 20 min, with an average fluence of 3.8 × 1012/cm2, was conducted at KUR's heavy water neutron irradiation facility. Subsequently, all of the rats were monitored under identical conditions for 7 days, with pre- and post-irradiation tumor size assessed through MRI and pathological examination. The results indicate a remarkable therapeutic efficacy in both BPA-administered groups (CSF and IV). Notably, the rats treated with CSF administration exhibited diminished BPA accumulation in normal tissue compared to those treated with IV administration, alongside maintaining excellent overall health. Thus, CSF-based BPA administration holds promise as a novel drug delivery mechanism in BNCT. [ABSTRACT FROM AUTHOR]

Glioblastoma is a highly aggressive glioma with limited treatment options. Boron neutron capture therapy (BNCT) offers a promising approach for refractory cancers, utilizing boron-10 (10B) and thermal neutrons to generate cytotoxic particles. Effective BNCT depends on selective targeting and retention of 10B in tumors. Current BNCT drugs face issues with rapid clearance and poor tumor accumulation. To address this, we developed gold nanoparticles (AuNPs) functionalized with cyclic arginine-glycine-aspartic acid (cRGD) peptides as a nanocarrier for Sodium Mercaptododecaborate (BSH), resulting in AuNPs-BSH&PEG-cRGD. In vitro, AuNPs-BSH&PEG-cRGD increased 10B content in GL261 glioma cells by approximately 2.5-fold compared to unmodified AuNPs-BSH&PEG, indicating enhanced targeting due to cRGD's affinity for integrin receptor αvβ3. In a subcutaneous glioma mouse model, 6 h post-intratumoral administration, the 10B concentration in tumors was 17.98 μg/g for AuNPs-BSH&PEG-cRGD, significantly higher than 0.45 μg/g for BSH. The tumor-to-blood (T/B) and tumor-to-normal tissue (T/N) ratios were also higher for AuNPs-BSH&PEG-cRGD, suggesting improved targeting and retention. This indicates that AuNPs-BSH&PEG-cRGD may enhance BNCT efficacy and minimize normal tissue toxicity. In summary, this study provides a novel strategy for BSH delivery and may broaden the design vision of BNCT nano-boron capture agents. [ABSTRACT FROM AUTHOR]

Boron Neutron Capture Therapy (BNCT) is performed using high-intensity neutron sources; however, the energy of the primary neutrons is too high for direct patient irradiation. Thus, neutron moderation is mandatory and is performed using a device known as a Beam Shaping Assembly (BSA). Due to the differences in flux and energy spectra between neutron sources, each facility needs a dedicated BSA design, whether it is based on a nuclear reactor or, more recently, on an accelerator. Since moderation involves the loss of neutrons, typically by a factor of 1000, it is necessary to generate a very high flux before neutrons pass through the BSA. We propose a novel approach that eliminates the necessity of a BSA, BSA-free, by generating neutrons suitable in flux and energy for direct patient irradiation through the Sc(p,n) Ti reaction using near-threshold protons. Our findings demonstrate that all IAEA quality factors for BNCT can be met with existing proton accelerators. Additionally, figures of merit studied provide similar results compared to real BNCT facilities. This breakthrough opens up new avenues in BNCT, among others, the control of the neutron penetration within the human body by small changing in the proton energy. Also, it is expected simplified accelerator-based facilities in terms of manufacturing and maintenance and operation. This work is a study based on experimental data and Monte Carlo simulations. Technical challenges and safety are addressed in Discussion section. This novel proposal is under evaluation as patent. [ABSTRACT FROM AUTHOR]

Melanoma, the most aggressive skin cancer type, is challenging to treat due to its high metastatic potential and low response to conventional therapies. Innovative approaches, including combination therapies, are crucial for enhancing treatment efficacy while minimizing side effects. It is developed boronophenylalanine‐containing polydopaine (B‐PDA) nanoparticles by encapsulating boronophenylalanine in polydopamine through nitrogen‐boronate coordination, targeting both boron neutron capture therapy (BNCT) and photothermal therapy (PTT). With stability and biocompatibility under physiological conditions, these nanoparticles utilize the phenylalanine residues in BPA to target the overexpressed neutral amino acid transporter 1 (LAT1) in melanoma cells, resulting in enhanced cell‐specific targeting. B‐PDA nanoparticles demonstrated significant photothermal effects under external stimulation, inducing localized heating and triggering heterogeneous tumor cell death, thereby enhancing sensitivity to BNCT. Combining BNCT and PTT, the B‐PDA nanoparticles offer a promising strategy for melanoma treatment. [ABSTRACT FROM AUTHOR]

Radiated tumor cell‐derived extracellular vesicles (RT‐EVs) encapsulate abundant DNA fragments from irradiated tumor cells, in addition to acting as integrators of multiple tumor antigens. Accumulating evidence indicates these DNA fragments from damaged cells are involved in downstream immune responses, but most of them are degraded in cells before incorporation into derived RT‐EVs, thus the low abundance of DNA fragments limits immune responses of RT‐EVs. Here, this study found that different radiations affected fates of DNA fragments in RT‐EVs. Boron neutron capture therapy (BNCT) induced DNA accumulation in RT‐EVs (BEVs) by causing more DNA breaks and DNA oxidation resisting nuclease degradation. This is attributed to the high‐linear energy transfer (LET) properties of alpha particles from the neutron capture reaction of 10B. When being internalized by dendritic cells (DCs), BEVs activated the DNA sensing pathway, resulting in functional enhancements including antigen presentation, migration capacity, and cytokine secretion. After vaccination of the BEVs‐educated DCs (BEV@BMDCs), the effector T cells significantly expanded and infiltrated into tumors, suggesting robust anti‐tumor immune activation. BEV@BMDCs not only effectively inhibited the primary tumor growth and metastasis formation but also elicited long‐term immune memory. In conclusion, a successful DC vaccine is provided as a promising candidate for tumor vaccine. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Accelerator‐based boron neutron capture therapy (AB‐BNCT) systems are becoming commercially available and are expected to be widely used in hospitals. To ensure the safety of BNCT, establishing a quality assurance (QA) program and properly managing the stability of the system are necessary. In particular, a high level of beam output stability is required to avoid accidents because beam output is a major factor in patient dose. However, no studies have analyzed the long‐term beam output stability of AB‐BNCT systems.This study aimed to retrospectively analyze the long‐term stability of the beam output by statistical process control (SPC) based on the QA results over 3 years.The data analyzed are the results of daily QA (DQA) and weekly QA (WQA) in an AB‐BNCT system and were taken between June 2020 and September 2023. The evaluation of the stability of the beam output was based on the reaction rate between gold and neutrons calculated using the activation foil method using a gold foil. In DQA, which can be performed in a short time, the gold foil was applied directly to the beam irradiation aperture in air. In WQA, measurements were performed at the phantom surface, 2‐cm depth, and 6‐cm depth using a dedicated water phantom. The acquired data were retrospectively analyzed by individuals and a moving range chart (I‐MR chart), exponentially weighted moving average control chart (EWMA chart), and several process capability indexes (PCIs).Over 99% of the DQA I‐MR chart results were within control limits, whereas the WQA I‐MR chart results showed that 1.8%, 4.1%, and 2.0% of the measurements exceeded the control limits at the surface, 2‐cm depth, and 6‐cm depth, respectively. The variation in the reaction rate of the gold foil before and after the replacement of the target was <0.5%. The EWMA chart results revealed no significant beam output drift for either DQA or WQA. Most measured data were normal based on the results of the Anderson–Darling test and met the requirements for PCI evaluation; most PCI values were >1.0; however, the Cpmk of DQA and the 2‐ and 6‐cm depth WQAs between August 2021 and November 2022 in treatment course 2 were 0.83, 0.77, and 0.87, respectively, which were <1.0.The long‐term stability of beam output was confirmed using SPC in an AB‐BNCT system. The results of the control chart revealed no significant variation or drift in the beam output, and the quantitative evaluation using PCI revealed high stability. A routine QA program will enable us to provide safe BNCT. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Targeted radiotherapies with low‐energy ions show interesting possibilities for the selective irradiation of tumor cells, a strategy particularly appropriate for the treatment of disseminated cancer. Two promising examples are boron neutron capture therapy (BNCT) and targeted radionuclide therapy with α$\alpha$‐particle emitters (TAT). The successful clinical translation of these radiotherapies requires the implementation of accurate radiation dosimetry approaches able to take into account the impact on treatments of the biological effectiveness of ions and the heterogeneity in the therapeutic agent distribution inside the tumor cells. To this end, biophysical models can be applied to translate the interactions of radiations with matter into biological endpoints, such as cell survival.The NanOx model was initially developed for predicting the cell survival fractions resulting from irradiations with the high‐energy ion beams encountered in hadrontherapy. We present in this work a new implementation of the model that extends its application to irradiations with low‐energy ions, as the ones found in TAT and BNCT.The NanOx model was adapted to consider the energy loss of primary ions within the sensitive volume (i.e., the cell nucleus). Additional assumptions were introduced to simplify the practical implementation of the model and reduce computation time. In particular, for low‐energy ions the narrow‐track approximation allowed to neglect the energy deposited by secondary electrons outside the sensitive volume, increasing significantly the performance of simulations. Calculations were performed to compare the original hadrontherapy implementation of the NanOx model with the present one in terms of the inactivation cross sections of human salivary gland cells as a function of the kinetic energy of incident α$\alpha$‐particles.The predictions of the previous and current versions of NanOx agreed for incident energies higher than 1 MeV/n. For lower energies, the new NanOx implementation predicted a decrease in the inactivation cross sections that depended on the length of the sensitive volume.We reported in this work an extension of the NanOx biophysical model to consider irradiations with low‐energy ions, such as the ones found in TAT and BNCT. The excellent agreement observed at intermediate and high energies between the original hadrontherapy implementation and the present one showed that NanOx offers a consistent, self‐integrated framework for describing the biological effects induced by ion irradiations. Future work will focus on the application of the latest version of NanOx to cases closer to the clinical setting. [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]

Background: In advanced head and neck cancer (HNC) patients, 50–60% experience loco-regional relapse and distant metastasis. Boron neutron capture therapy (BNCT) has shown remarkable therapeutic response in recurrent HNC, but there is still a 70% chance of local recurrence. This study aimed to identify a suitable liquid biomarker to assess patient response following BNCT. Myeloid-derived suppressor cells (MDSCs) are immune-suppressive cells that inhibit cytotoxic T cells. Circulating MDSC levels have been linked to the clinical stage and prognosis in HNSCC. Methods: Five patients with recurrent head and neck cancer underwent a treatment regimen that commenced with BNCT, followed by fractionated image-guided intensity-modulated radiotherapy (IG-IMRT). Liquid biopsy analysis via flow cytometry and tumor volume analysis by clinical imaging were conducted at three stages: before BNCT, before the first fraction of IG-IMRT, and one month after the last fraction of IG-IMRT. Results: Compared to other MDSC subtypes, monocytic MDSCs (M-MDSCs) exhibited a notable correlation with tumor volume. This strong correlation was observed at all testing time points except one month after BNCT treatment. Conclusions: This case series highlights a strong link between tumor size and circulating M-MDSC levels before BNCT and one month after the last IG-IMRT treatment in recurrent head and neck cancer patients. These results suggest that the level of circulating M-MDSCs could be a marker for monitoring tumor progression in recurrent HNC patients following radiation therapy, including BNCT. [ABSTRACT FROM AUTHOR]

This study introduces the MKM_B model, an approach derived from the MKM model, designed to evaluate the biological effectiveness of Boron Neutron Capture Therapy (BNCT) in the face of challenges from varying microscopic boron distributions. The model introduces a boron compensation factor, allowing for the assessment of compound Biological Effectiveness (CBE) values for different boron distributions. Utilizing the TOPAS simulation platform, the lineal energy spectrum of particles in BNCT was simulated, and the sensitivity of the MKM_B model to parameter variations and the influence of cell size on the model were thoroughly investigated. The CBE values for 10B-boronphenylalanine (BPA) and 10B-sodium (BSH) were determined to be 3.70 and 1.75, respectively. These calculations were based on using the nucleus radius of 2.5 μm and the cell radius of 5 μm while considering a 50% surviving fraction. It was observed that as cell size decreased, the CBE values for both BPA and BSH increased. Additionally, the model parameter rd was identified as having the most significant impact on CBE, with other parameters showing moderate effects. The development of the MKM_B model enables the accurate prediction of CBE under different boron distributions in BNCT. This model offers a promising approach to optimize treatment planning by providing increased accuracy in biological effectiveness. [ABSTRACT FROM AUTHOR]

This study aimed to identify the required capabilities and workload of medical staff in accelerator-based boron neutron capture therapy (BNCT). From August to September 2022, a questionnaire related to the capabilities and workload in the accelerator-based BNCT was administered to 12 physicians, 7 medical physicists and 7 radiological technologists engaged in BNCT and 6 other medical physicists who were not engaged in BNCT to compare the results acquired by those engaged in BNCT. Only 6–21% of patients referred for BNCT received it. Furthermore, 30–75% of patients who received BNCT were treated at facilities located within their local district. The median required workload per treatment was 55 h. Considering additional workloads for ineligible patients, the required workload reached ~1.2 times longer than those for only eligible patients' treatment. With respect to capabilities, discrepancies were observed in treatment planning, quality assurance and quality control, and commissioning between medical physicists and radiological technologists. Furthermore, the specialized skills required by medical physicists are impossible to acquire from the experience of conventional radiotherapies as physicians engaged in BNCT were specialized not only in radiation oncology, but also in other fields. This study indicated the required workload and staff capabilities for conducting accelerator-based BNCT considering actual clinical conditions. The workload required for BNCT depends on the occupation. It is necessary to establish an educational program and certification system for the skills required to safely and effectively provide BNCT to patients. [ABSTRACT FROM AUTHOR]

Diamond as a templating substrate is largely unexplored, and the unique properties of diamond, including its large bandgap, thermal conductance, and lack of cytotoxicity, makes it versatile in emergent technologies in medicine and quantum sensing. Surface termination of an inert diamond substrate and its chemical reactivity are key in generating new bonds for nucleation and growth of an overlayer material. Oxidized high-pressure high temperature (HPHT) nanodiamonds (NDs) are largely terminated by alcohols that act as nucleophiles to initiate covalent bond formation when an electrophilic reactant is available. In this work, we demonstrate a templated synthesis of ultrathin boron on ND surfaces using trigonal boron compounds. Boron trichloride (BCl3), boron tribromide (BBr3), and borane (BH3) were found to react with ND substrates at room temperature in inert conditions. BBr3 and BCl3 were highly reactive with the diamond surface, and sheet-like structures were produced and verified with electron microscopy. Surface-sensitive spectroscopies were used to probe the molecular and atomic structure of the ND constructs' surface, and quantification showed the boron shell was less than 1 nm thick after 1–24 h reactions. Observation of the reaction supports a self-terminating mechanism, similar to atomic layer deposition growth, and is likely due to the quenching of alcohols on the diamond surface. X-ray absorption spectroscopy revealed that boron-termination generated midgap electronic states that were originally predicted by density functional theory (DFT) several years ago. DFT also predicted a negative electron surface, which has yet to be confirmed experimentally here. The boron-diamond nanostructures were found to aggregate in dichloromethane and were dispersed in various solvents and characterized with dynamic light scattering for future cell imaging or cancer therapy applications using boron neutron capture therapy (BNCT). The unique templating mechanism based on nucleophilic alcohols and electrophilic trigonal precursors allows for covalent bond formation and will be of interest to researchers using diamond for quantum sensing, additive manufacturing, BNCT, and potentially as an electron emitter. [ABSTRACT FROM AUTHOR]

Recent advancements in medical dosimetry have significantly improved the precision and effectiveness of radiation therapy by accurately quantifying absorbed doses from ionizing radiation. In the past, conventional one-dimensional and two-dimensional dosimeters were commonly used, but recent years have seen a surge in interest in 3D dosimeters for complex radiation therapies. This review aims to elucidate the applications of 3D polymer gel dosimeters in radiation therapies, covering diverse radiation and energy fields. Utilizing an extensive search strategy across various electronic databases, the review synthesizes insights from recent studies on polymer gel dosimeters, exploring their properties and applications in ultrasound, optical coherence tomography, magnetic resonance imaging, and computed tomography. Furthermore, the review investigates the consideration of Monte Carlo simulations in modeling dosimeter applications in radiation therapy, examining specific parameters affecting dosimeter performance. It provides a comprehensive synthesis of available data over the past decade, shedding light on the medical applications of 3D polymer gel dosimeters and their potential limitations. Finally, the review discusses challenges in widespread implementation and future directions, emphasizing the need for further research on novel gel dosimeters and the incorporation of nanoparticles to enhance sensitivity and functionality in medical dosimetry. [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]

Laryngeal preservation and a radical cure are the treatment goals for laryngeal carcinoma, and larynx-preserving therapy is generally preferred for early-stage laryngeal carcinoma. When laryngeal carcinoma recurs locally, patients are often forced to undergo total laryngectomy, resulting in loss of vocal function. However, many patients with laryngeal carcinoma who have residual or recurrent disease after radiotherapy wish to preserve their voice. The purpose of this study was to investigate the possibility of using BNCT as a larynx-preserving treatment for residual or recurrent laryngeal carcinomas following radical irradiation. This study included 15 patients who underwent BNCT for residual or recurrent laryngeal carcinoma after radical laryngeal carcinoma irradiation. The number of treatment sessions for all patients was one irradiation. Before BNCT, the recurrent laryngeal carcinoma stage was rT1aN0, rT2N0, rT2N1, rT3N0, rT3N1, and rT4aN0 in one, six, one, three, one, and three patients, respectively. The median maximum tumor diameter before BNCT was 15 mm (8–22 mm). All patients underwent a tracheostomy before BNCT to mitigate the risk of upper airway stenosis due to laryngeal edema after BNCT. Treatment efficacy was evaluated retrospectively using monthly laryngoscopy after BNCT and contrast-enhanced CT scans at 3 months. The safety of treatment was evaluated based on examination findings and interviews with patients. The median hospital stay after BNCT was 2 days (1–6). The response rate at three months after BNCT in 15 patients with locally recurrent laryngeal carcinoma was 93.3 %, and the CR rate was 73.3 %. The most frequent adverse event associated with BNCT was laryngeal edema, which occurred in nine patients the day after BNCT. The average course of laryngeal edema peaked on the second day after BNCT and almost recovered after 1 week in all patients. One patient had bilateral vocal fold movement disorders. None had dyspnea because of prophylactic tracheostomy. No grade four or higher adverse events occurred. Other grade 2 adverse events included pharyngeal mucositis, diarrhea, and sore throat. Three months after BNCT, tracheostomy tubes were removed in nine patients, retinal cannulas were placed in three patients, and voice cannulas were placed in three patients. BNCT for locally recurrent laryngeal carcinoma can safely deliver radical irradiation to tumor tissues, even in patients undergoing radical irradiation. BNCT has shown antitumor effects against recurrent laryngeal carcinoma. However, further long-term observations of the treatment outcomes are required. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a unique radiotherapy of selectively eradicating tumor cells using boron compounds (e.g., 4-borono-l-phenylalanine [BPA]) that are heterogeneously taken up at the cellular level. Such heterogenicity potentially reduces the curative efficiency. However, the effects of temporospatial heterogenicity on cell killing remain unclear. With the technical combination of radiation track detector and biophysical simulations, this study revealed the cell cycle-dependent heterogenicity of BPA uptake and subsequent biological effects of BNCT on HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators, as well as the modification effects of polyvinyl alcohol (PVA). The results showed that the BPA concentration in the S/G2/M phase was higher than that in the G1/S phase and that PVA enhances the biological effects both by improving the uptake and by canceling the heterogenicity. These findings might contribute to a maximization of therapeutic efficacy when BNCT is combined with PVA and/or cell cycle-specific anticancer agents. [ABSTRACT FROM AUTHOR]

The ANTHEM (Advanced Technologies for Human-centered Medicine) Radio-Frequency Quadrupole (RFQ) will employ eight coaxial power couplers, which will be magnetically coupled to the device through a loop antenna. The coupler design can support up to 140 kW in continuous wave operation. This paper presents the design of the cavity used for high-power testing, with the primary objectives of both optimizing the coupling between the couplers and ensuring operations at the designated operating frequency. Furthermore, the paper encompasses thermal and structural assessments conducted through numerical simulations. [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]

Purpose: Neutron capture therapy (NCT) by 10B and 157Gd agents is a unique irradiation‐based method which can be used to treat brain tumors. Current study aims to quantitatively evaluate the relative biological effectiveness (RBE) and dose distributions during the combined BNCT and GdNCT modalities through a hybrid Monte Carlo (MC) simulation approach. Methods: Snyder head phantom as well as a cubic hypothetical tumor was at first modeled by Geant4 MC Code. Then, the energy spectra and dose distribution relevant to the released secondary particles during the combined Gd/BNCT were scored for different concentrations of 157Gd and 10B inside tumor volume. Finally, the scored energy spectra were imported to the MCDS code to estimate both RBESSB and RBEDSB values for different 157Gd concentrations. Results: The results showed that combined Gd/BNCT increases the fluence‐averaged RBESSB values by about 1.7 times when 157Gd concentration increments from 0 to 2000 µg/g for both considered cell oxygen levels (pO2 = 10% and 100%). Besides, a reduction of about 26% was found for fluence‐averaged RBEDSB values with an increment of 157Gd concentration in tumor volume. Conclusion: From the results, it can be concluded that combined Gd/BNCT technique can improve tumor coverage with higher dose levels but in the expense of RBEDSB reduction which can affect the clinical efficacy of the NCT technique. [ABSTRACT FROM AUTHOR]

The document "Application of Nanomaterials in Biomedical Imaging and Cancer Therapy II" explores the cutting-edge advances in using nanomaterials for cancer imaging and therapy. It focuses on integrating nanoparticles in cancer research to address challenges like treatment specificity and enhancing traditional therapies. The studies presented in the document highlight the development of multifunctional nanocomposites, nanoparticle-based drug delivery systems, and innovations in imaging modalities and radiotherapy dose enhancement. Overall, the document emphasizes the potential of nanomaterials to improve cancer treatment outcomes and pave the way for clinical translation, while addressing challenges such as biocompatibility and safety. [Extracted from the article]

Tumor-to-normal ratio (T/N) measurement of 18F-FBPA is crucial for patient eligibility to receive boron neutron capture therapy. This study aims to compare the difference in standard uptake value ratios on brain tumors and normal brains using PET/MR ZTE and atlas-based attenuation correction with the current standard PET/CT attenuation correction. Regarding the normal brain uptake, the difference was not significant between PET/CT and PET/MR attenuation correction methods. The T/N ratio of PET/CT-AC, PET/MR ZTE-AC and PET/MR AB-AC were 2.34 ± 0.95, 2.29 ± 0.88, and 2.19 ± 0.80, respectively. The T/N ratio comparison showed no significance using PET/CT-AC and PET/MR ZTE-AC. As for the PET/MRI AB-AC, significantly lower T/N ratio was observed (− 5.18 ± 9.52%; p < 0.05). The T/N difference between ZTE-AC and AB-AC was also significant (4.71 ± 5.80%; p < 0.01). Our findings suggested PET/MRI imaging using ZTE-AC provided superior quantification on 18F-FBPA-PET compared to atlas-based AC. Using ZTE-AC on 18F-FBPA-PET /MRI might be crucial for BNCT pre-treatment planning. [ABSTRACT FROM AUTHOR]

Background: Monte Carlo simulation code is commonly used for the dose calculation of boron neutron capture therapy. In the past, dose calculation was performed assuming a homogeneous mass density and elemental composition inside the tissue, regardless of the patient's age or sex. Studies have shown that the mass density varies with patient to patient, particularly for those that have undergone surgery or radiotherapy. A method to convert computed tomography numbers into mass density and elemental weights of tissues has been developed and applied in the dose calculation process using Monte Carlo codes. A recent study has shown the variation in the computed tomography number between different scanners for low‐ and high‐density materials. Purpose: The aim of this study is to investigate the effect of the elemental composition inside each calculation voxel on the dose calculation and the application of the stoichiometric CT number calibration method for boron neutron capture therapy planning. Methods: Monte Carlo simulation package Particle and Heavy Ion Transport code System was used for the dose calculation. Firstly, a homogeneous cubic phantom with the material set to ICRU soft tissue (four component), muscle, fat, and brain was modelled and the NeuCure BNCT system accelerator‐based neutron source was used. The central axis depth dose distribution was simulated and compared between the four materials. Secondly, a treatment plan of the brain and the head and neck region was simulated using a dummy patient dataset. Three models were generated; (1) a model where only the fundamental materials were considered (simple model), a model where each voxel was assigned a mass density and elemental weight using (2) the Nakao20 model, and (3) the Schneider00 model. The irradiation conditions were kept the same between the different models (irradiation time and irradiation field size) and the near maximum (D1%) and mean dose to the organs at risk were calculated and compared. Results: A maximum percentage difference of approximately 5% was observed between the different materials for the homogeneous phantom. With the dummy patient plan, a large dose difference in the bone (greater than 12%) and region near the low‐density material (mucosal membrane, 7%–11%) was found between the different models. Conclusions: A stoichiometric CT number calibration method using the newly developed Nakao20 model was applied to BNCT dose calculation. The results indicate the importance of calibrating the CT number to elemental composition for each individual CT scanner for the purpose of BNCT dose calculation along with the consideration of heterogeneity of the material composition inside the defined region of interest. [ABSTRACT FROM AUTHOR]

Background: In boron neutron capture therapy (BNCT)—a form of binary radiotherapy—the primary challenge in treatment planning systems for dose calculations arises from the time‐consuming nature of the Monte Carlo (MC) method. Recent progress, including the use of neural networks (NN), has been made to accelerate BNCT dose calculations. However, this approach may result in significant dose errors in both the tumor and the skin, with the latter being a critical organ in BNCT. Furthermore, owing to the lack of physical processes in purely NN‐based approaches, their reliability for clinical dose calculations in BNCT is questionable. Purpose: In this study, a physically constrained MC–NN (PCMC–NN) coupling algorithm is proposed to achieve fast and accurate computation of the BNCT three‐dimensional (3D) therapeutic dose distribution. This approach synergizes the high precision of the MC method with the speed of the NN and utilizes physical conservation laws to constrain the coupling process. It addresses the time‐consuming issue of the traditional MC method while reducing dose errors. Methods: Clinical data were collected from 113 glioblastoma patients. For each patient, the 3D dose distributions for both the coarse and detailed dose grids were calculated using the MC code PHITS. Among these patients, the data from 14 patients were allocated to the test set, 9 to the validation set, and the remaining to the training set. A neural network, 3D‐Unet, was built based on the coarse grid dose and patient CT information to enable fast and accurate computation of the 3D detailed grid dose distribution of BNCT. Results: Statistical evaluations, including relative deviation, dose deviation, mean absolute error (MAE), and mean absolute percentage error (MAPE) were conducted. Our findings suggested that the PCMC–NN algorithm substantially outperformed the traditional NN and interpolation methods. Furthermore, the proposed algorithm significantly reduced errors, particularly in the skin and GTV, and improved computational accuracy (hereinafter referred to simply as 'accuracy') with a MAPE range of 1.6%–4.0% and a maximum MAE of 0.3 Gy (IsoE) for different organs. The dose–volume histograms generated by the PCMC–NN aligned well with those obtained from the MC method, further validating its accuracy. Conclusions: The PCMC–NN algorithm enhanced the speed and accuracy of BNCT dose calculations by combining the MC method with the NN algorithm. This indicates the significant potential of the proposed algorithm for clinical applications in optimizing treatment planning. [ABSTRACT FROM AUTHOR]

Purpose: Since June 2020, boron neutron capture therapy (BNCT) has been a health care service covered by health insurance in Japan to treat locally advanced or recurrent unresectable head and neck cancers. Therefore, we aimed to assess the clinical outcomes of BNCT as a health insurance treatment and explore its role among the standard treatment modalities for head and neck cancers. Materials and Methods: We retrospectively analyzed data from patients who were treated using BNCT at Kansai BNCT Medical Center, Osaka Medical and Pharmaceutical University, between June 2020 and May 2022. We assessed objective response rates based on the Response Evaluation Criteria in Solid Tumors version 1.1, and adverse events based on the Common Terminology Criteria for Adverse Events, version 5.0. Additionally, we conducted a survival analysis and explored the factors that contributed to the treatment results. Results: Sixty‐nine patients (72 treatments) were included in the study, with a median observation period of 15 months. The objective response rate was 80.5%, and the 1‐year locoregional control, progression‐free survival, and overall survival rates were 57.1% (95% confidence interval [CI]: 43.9%–68.3%), 42.2% (95% CI: 30.1%–53.8%), and 75.4% (95% CI: 62.5%–84.5%), respectively. Locoregional control was significantly longer in patients with earlier TNM staging and no history of chemotherapy. Conclusions: BNCT may be an effective treatment option for locally advanced or recurrent unresectable head and neck cancers with no other definitive therapies. If definitive surgery or radiation therapy are not feasible, BNCT should be considered at early disease stages. [ABSTRACT FROM AUTHOR]

Alkylation of 9-methylthio-nido-carborane under the action of the corresponding iodo derivatives of alanine and homoalanine furnished new (nido-carboran-9-yl) derivatives of (R)-cysteine and (S)-methionine. The synthesized chiral nido-carborane derivatives contain asymmetric carbon and sulfur atoms, as well as a chiral plane. The developed approach to the synthesis of sulfur-containing B(9)-substituted nido-carborane derivatives can be used in the preparation of bioactive compounds, including potential boron delivery agents for boron neutron capture therapy of oncological diseases. [ABSTRACT FROM AUTHOR]

Boron Neutron Capture Therapy (BNCT) is a promising radiotherapy technique for cancer treatment. Optimizing dose distribution in tumors is a significant challenge for BNCT, especially for tumors that are deep-seated. The method of optimizing dose distribution through multi-field irradiation holds great potential for clinical applications in BNCT. This study presents an optimization program that couples genetic algorithm and Monte Carlo simulation, which can automatically optimize irradiation field weights for multi-field irradiation, ensuring optimal dose distribution for cancer patients. Using this program, a glioblastoma case was used to analyze the optimization results for different numbers of irradiation fields. The results demonstrate that the program possesses an efficient and accurate automatic optimization feature for multi-field irradiation weights. The minimum dose, mean dose, and D80% of tumor dose improve with the increase in irradiation fields, while the homogeneity index (HI) of tumor dose decreases, without exceeding dose constraints for organs at risk. The developed optimization program provides a method for determining irradiation field weights in BNCT treatment planning systems, which has the potential to improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Nanoparticles composed of inorganic boron-containing compounds represent a promising candidate as 10B carriers for BNCT. This study focuses on the synthesis, characterization, and assessment of the biological activity of composite nanomaterials based on boron carbide (B4C). Boron carbide is a compelling alternative to borated molecules due to its high volumetric B content, prolonged retention in biological systems, and low toxicity. These attributes lead to a substantial accumulation of B in tissues, eliminating the need for isotopically enriched compounds. In our approach, B4C nanoparticles were included in composite nanostructures with ultrasmall superparamagnetic nanoparticles (SPIONs), coated with poly (acrylic acid), and further functionalized with the fluorophore DiI. The successful internalization of these nanoparticles in HeLa cells was confirmed, and a significant uptake of 10B was observed. Micro-distribution studies were conducted using intracellular neutron autoradiography, providing valuable insights into the spatial distribution of the nanoparticles within cells. These findings strongly indicate that the developed nanomaterials hold significant promise as effective carriers for 10B in BNCT, showcasing their potential for advancing cancer treatment methodologies. [ABSTRACT FROM AUTHOR]

Accelerator-based boron neutron capture therapy (BNCT) systems employing a solid-state lithium target indicated the reduction of neutron flux over the lifetime of a target, and its reduction could represent the neutron flux model. This study proposes a novel compensatory approach for delivering the required neutron fluence and validates its clinical applicability. The proposed approach relies on the neutron flux model and the cumulative sum of real-time measurements of proton charges. The accuracy of delivering the required neutron fluence for BNCT using the proposed approach was examined in five Li targets. With the proposed approach, the required neutron fluence could be delivered within 3.0%, and within 1.0% in most cases. However, those without using the proposed approach exceeded 3.0% in some cases. The proposed approach can consider the neutron flux reduction adequately and decrease the effect of uncertainty in neutron measurements. Therefore, the proposed approach can improve the accuracy of delivering the required fluence for BNCT even if a neutron flux reduction is expected during treatment and over the lifetime of the Li target. Additionally, by adequately revising the approach, it may apply to other type of BNCT systems employing a Li target, furthering research in this direction. [ABSTRACT FROM AUTHOR]

Purpose: Boramino acids are a class of amino acid biomimics that replace the carboxylate group with trifluoroborate and can achieve the 18F-labeled positron emission tomography (PET) and boron neutron capture therapy (BNCT) with identical chemical structure. Methods: This study reports a trifluoroborate-derived boronophenylalanine (BBPA), a derived boronophenylalanine (BPA) for BNCT, as a promising PET tracer for tumor imaging. Results: Competition inhibition assays in cancer cells suggested the cell accumulation of [18F]BBPA is through large neutral amino acid transporter type-1 (LAT-1). Of note, [18F]BBPA is a pan-cancer probe that shows notable tumor uptake in B16-F10 tumor-bearing mice. In the patients with gliomas and metastatic brain tumors, [18F]BBPA-PET shows good tumor uptake and notable tumor-to-normal brain ratio (T/N ratio, 18.7 ± 5.5, n = 11), higher than common amino acid PET tracers. The [18F]BBPA-PET quantitative parameters exhibited no difference in diverse contrast-enhanced status (P = 0.115–0.687) suggesting the [18F]BBPA uptake was independent from MRI contrast-enhancement. Conclusion: This study outlines a clinical trial with [18F]BBPA to achieve higher tumor-specific accumulation for PET, provides a potential technique for brain tumor diagnosis, and might facilitate the BNCT of brain tumors. [ABSTRACT FROM AUTHOR]

In this research, we developed boron-rich nanoparticles that can be used for boron neutron capture therapy as potential carriers for boron delivery to cancerous tissues. Functionalized carbonated boron nitride nanostructures (CBNs) were successfully synthesized in self-propagating combustion waves in mixtures of high-nitrogen explosives and boron compounds. The products' composition, morphology, and structural features were investigated using Fourier transform infrared spectroscopy, powder X-ray diffraction, low-temperature nitrogen sorption analysis, thermogravimetric analysis, high-resolution scanning electron microscopy, and high-resolution transmission electron microscopy. The extreme conditions prevailing in combustion waves favor the formation of nanosized CBN hollow grains with highly disordered structures that are properly functionalized on the surface and inside the particles. Therefore, they are characterized by high porosity and good dispersibility in water, which are necessary for medical applications. During biological tests, a concentration-dependent effect of the obtained boron nitride preparations on the viability of normal and neoplastic cells was demonstrated. Moreover, the assessment of the degree of binding of fluorescently labeled nanoparticles to selected cells confirmed the relationships between the cell types and the concentration of the preparation at different incubation time points. [ABSTRACT FROM AUTHOR]

Given the renewed interest in boron neutron capture therapy (BNCT) and the intensified search for improved boron carriers, as well as the difficulties of coherently comparing the carriers described so far, it seems necessary to define a basic set of assays and standardized methods to be used in the early stages of boron carrier development in vitro. The selection of assays and corresponding methods is based on the practical experience of the authors and is certainly not exhaustive, but open to discussion. The proposed tests/characteristics: Solubility, lipophilicity, stability, cytotoxicity, and cellular uptake apply to both low molecular weight (up to 500 Da) and high molecular weight (5000 Da and more) boron carriers. However, the specific methods have been selected primarily for low molecular weight boron carriers; in the case of high molecular weight compounds, some of the methods may need to be adapted. [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]

Although boron neutron capture therapy (BNCT) causes minor damage to normal cells owing to the nuclear reactions induced by neutrons with major elements of tissues such as hydrogen and nitrogen, it is useful to estimate the accurate exposure dose for radiation protection. This study aims to estimate the contribution of internal exposure in radiation exposure dose for BNCT. The study was performed by referring to clinical studies at a reactor-based BNCT facility on the basis of computational dosimetry. Five irradiation regions of head and neck were selected for the estimation. The results suggest that external exposure occurred primarily in and around the irradiation field. Furthermore, during the exposure dose estimation in BNCT, internal exposure was found to be not negligible, implying that the irradiation regions in treatment planning must be considered for avoiding damage to certain critical organs that are susceptible to internal exposure. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy is a perspective selective technology for the destruction of cancer cells, while the use of lithium instead of boron may represent a new and promising vector for the development of neutron capture therapy (NCT). The aim of the study was a comparative assessment of the cytotoxicity of various lithium salts, as well as an analysis of the accumulation of lithium in tumor cells in vitro to determine the possibility of using lithium in NCT. The cytotoxicity of lithium salts was determined using MTT‐test and colony forming assay on human fibroblasts BJ‐5ta, human skin melanoma SK‐Mel‐28, and mouse skin melanoma B16 cell lines. An assessment of lithium concentration in cells was performed using inductively coupled plasma atomic emission spectrometry. Our results showed that three different lithium salts at a concentration of 40 μg/ml are not toxic for both tumor and normal cells. The highest uptake values were obtained on murine melanoma B16 cells when exposed to lithium carbonate (0.8 μg/106 cells); however, human melanoma SK‐Mel‐28 cells effectively accumulated both lithium carbonate and lithium citrate (about 0.46 μg/106 cells for two salts). Thus, our results demonstrate a range of non‐toxic doses of lithium salts and a high uptake of lithium by tumor cells, which indicates the possibility to use the lithium in NCT. The use of lithium instead of boron may represent a new and promising vector for the development of neutron capture therapy (NCT). The data obtained in this study demonstrate a range of non‐toxic doses of lithium carbonate, lithium citrate, and lithium chloride, as well as a high uptake of lithium by melanoma cells, that indicates the possibility to use the lithium in NCT. [ABSTRACT FROM AUTHOR]

Background: The use of cells as carriers for the delivery of nanoparticles is a promising approach in anticancer therapy, mainly due to their natural properties, such as biocompatibility and non-immunogenicity. Cellular carriers prevent the rapid degradation of nanoparticles, improve their distribution, reduce cytotoxicity and ensure selective delivery to the tumor microenvironment. Therefore, we propose the use of phagocytic cells as boron carbide nanoparticle carriers for boron delivery to the tumor microenvironment in boron neutron capture therapy. Results: Macrophages originating from cell lines and bone marrow showed a greater ability to interact with boron carbide (B4C) than dendritic cells, especially the preparation containing larger nanoparticles (B4C 2). Consequently, B4C 2 caused greater toxicity and induced the secretion of pro-inflammatory cytokines by these cells. However, migration assays demonstrated that macrophages loaded with B4C 1 migrated more efficiently than with B4C 2. Therefore, smaller nanoparticles (B4C 1) with lower toxicity but similar ability to activate macrophages proved to be more attractive. Conclusions: Macrophages could be promising cellular carriers for boron carbide nanoparticle delivery, especially B4C 1 to the tumor microenvironment and thus prospective use in boron neutron capture therapy. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a type of targeted particle radiation therapy with potential applications at the cellular level. Spinal cord gliomas (SCGs) present a substantial challenge owing to their poor prognosis and the lack of effective postoperative treatments. This study evaluated the efficacy of BNCT in a rat SCGs model employing the Basso, Beattie, and Bresnahan (BBB) scale to assess postoperative locomotor activity. We confirmed the presence of adequate in vitro boron concentrations in F98 rat glioma and 9L rat gliosarcoma cells exposed to boronophenylalanine (BPA) and in vivo tumor boron concentration 2.5 h after intravenous BPA administration. In vivo neutron irradiation significantly enhanced survival in the BNCT group when compared with that in the untreated group, with a minimal BBB scale reduction in all sham-operated groups. These findings highlight the potential of BNCT as a promising treatment option for SCGs. [ABSTRACT FROM AUTHOR]

Background: The current radiobiological model employed for boron neutron capture therapy (BNCT) treatment planning, which relies on microdosimetry, fails to provide an accurate representation the biological effects of BNCT. The precision in calculating the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) plays a pivotal role in determining the therapeutic efficacy of BNCT. Therefore, this study focuses on how to improve the accuracy of the biological effects of BNCT. Purpose: The purpose of this study is to propose new radiation biology models based on nanodosimetry to accurately assess RBE and CBE for BNCT. Methods: Nanodosimetry, rooted in ionization cluster size distributions (ICSD), introduces a novel approach to characterize radiation quality by effectively delineating RBE through the ion track structure at the nanoscale. In the context of prior research, this study presents a computational model for the nanoscale assessment of RBE and CBE. We establish a simplified model of DNA chromatin fiber using the Monte Carlo code TOPAS‐nBio to evaluate the applicability of ICSD to BNCT and compute nanodosimetric parameters. Results: Our investigation reveals that both homogeneous and heterogeneous nanodosimetric parameters, as well as the corresponding biological model coefficients α and β, along with RBE values, exhibit variations in response to varying intracellular 10B concentrations. Notably, the nanodosimetric parameter M1C2$M_1^{{{\mathrm{C}}}_2}$ effectively captures the fluctuations in model coefficients α and RBE. Conclusion: Our model facilitates a nanoscale analysis of BNCT, enabling predictions of nanodosimetric quantities for secondary ions as well as RBE, CBE, and other essential biological metrics related to the distribution of boron. This contribution significantly enhances the precision of RBE calculations and holds substantial promise for future applications in treatment planning. [ABSTRACT FROM AUTHOR]

Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment. [ABSTRACT FROM AUTHOR]

Silica nanoparticles synthesized solely from organosilanes naturally possess a greater number of organic functionalities than silica nanoparticles surface-modified with organosilanes. We report the synthesis of organically modified silica (ORMOSIL) nanoparticles with a mesoporous and surface-rough morphology and with a high surface area, made solely from vinyltrimethoxy silane. We chemically modified these vinyl silica nanoparticles using bromination and hydroboration, and demonstrated the high accessibility and reactivity of the vinyl groups with an ~85% conversion of the functional groups for the bromination of both particle types, a ~60% conversion of the functional groups for the hydroboration of surface-rough particles and a 90% conversion of the functional groups for the hydroboration of mesoporous particles. We determined that the mesoporous vinyl silica nanoparticles, while having a surface area that lies between the non-porous and surface-rough vinyl silica nanoparticles, provide the greatest accessibility to the vinyl groups for boronation and allow for the incorporating of up to 3.1 × 106 B atoms per particle, making the resulting materials attractive for boron neutron capture therapy. [ABSTRACT FROM AUTHOR]