Hiroki Tanaka

In this work, 4H-SiC neutron sensors (NSs) for boron neutron capture therapy were designed, fabricated, and tested under ultraviolet (UV) light and neutron irradiation. A pinned photodiode (PPD) structure and a parasitic bipolar junction transistor were designed for the NS region. A large neutron conversion layer of 500 µm × 500 µm was formed on the PPD area by ¹⁰ B ions implanted into a 700 nm Al layer. The output characteristics under UV light tests have demonstrated the functional operation of the 4T-active pixel sensor structure of SiC NSs. No significant degradation was observed under the E-3 tube, with a total neutron fluence of 1.8 × 10 ⁹ n cm ⁻² . The results, which were obtained under the heavy water neutron irradiation facility condition with a high neutron flux in the range of 1×10 ⁹ n c m − 2 s − 1 and a cycle of 1.0 s, demonstrated the neutron detection capability of the 4H-SiC NS prototypes, despite signs of degradation due to neutron-induced damage and the TID effects.

Ultra-high-dose-rate (UHDR) radiotherapy is expanding across modalities, but its mechanisms and optimal irradiation conditions remain unclear. This study aimed to establish a UHDR electron irradiation field using KURNS-LINAC to support research to elucidate the underlying mechanisms. The irradiation field was characterized through a comprehensive dosimetric evaluation using graphite blocks, radiochromic films, glass dosimeters, and Monte Carlo simulations. Single-shot irradiation experiments were conducted using 8 MeV electrons, and the dose rate at different distances from the beam port was evaluated. The results showed a monotonic decrease in the dose rate with increasing distance. The maximum pulse dose rate reached 8.07 × 10 ⁷ Gy s ⁻¹ , satisfying the conditions required for the FLASH effect. The two-dimensional dose distributions revealed beam broadening and a gradual reduction in the steep dose gradient with increasing distance due to air scattering. These findings demonstrate that the KURNS-LINAC can provide a flexible platform for UHDR irradiation.

Boron neutron capture therapy (BNCT) requires selective delivery of boron compounds to tumor cells to achieve therapeutic efficacy. In this study, a BNCT strategy centered on the sodium‐dependent multivitamin transporter (SMVT)‐targeted biotin‐conjugated boron compound, BBCIP, was evaluated, with selective incorporation of p‐boronophenylalanine (BPA) according to tumor transporter characteristics. To examine transporter‐dependent effects, the CRL1666 metastatic brain tumor model in rats was compared with an F98 glioma model, which exhibits distinct transporter expression profiles. The F98 model is characterized by dominant L‐type amino acid transporter 1 (LAT1) expression and low SMVT levels, whereas the CRL1666 model shows relatively high SMVT expression. BBCIP demonstrated stable and quantifiable intratumoral boron pharmacokinetics in both models. In BNCT experiments, BBCIP alone showed limited therapeutic efficacy in the LAT1‐dominant F98 model (median survival, 29 vs. 23 days in controls), whereas survival was further improved with the addition of BPA. In contrast, in the SMVT‐high CRL1666 model, BBCIP‐based BNCT significantly prolonged survival (30 vs. 15.5 days in controls), with only modest additional benefit from BPA. These findings indicate that the therapeutic contribution of BBCIP‐based BNCT depends on tumor transporter expression and that BPA may be advantageous in tumors with low SMVT expression. Rather than relying on a single boron carrier, these findings support a biology‐driven strategy in which boron agents are selected and combined according to tumor‐specific characteristics.

Purpose Boron neutron capture therapy (BNCT) is a tumor-selective radiation modality that delivers high–linear energy transfer alpha and Lithium-7 particles to boron-containing cells following neutron irradiation. While both preclinical and clinical investigations of BNCT for intracranial tumors have primarily focused on solitary lesions, brain metastases frequently present as multifocal disease in clinical practice. The therapeutic efficacy of BNCT in this setting remains insufficiently explored. Methods We evaluated the therapeutic efficacy of BNCT in rat models of solitary and multiple brain metastases established using a syngeneic breast cancer cell line. Boronophenylalanine was administered intravenously prior to neutron irradiation. Survival outcomes were compared among untreated controls, neutron irradiation alone, and BNCT groups. Boron biodistribution was analyzed to determine optimal irradiation timing, and treatment safety was assessed by longitudinal monitoring of body weight. Results BNCT significantly prolonged post-irradiation survival compared with neutron irradiation alone and untreated controls in both solitary and multiple tumor models. Notably, a substantial survival benefit was maintained even in the multiple brain metastasis model, despite the presence of spatially distributed intracranial tumor burden. Biodistribution analysis demonstrated preferential boron accumulation in tumor tissue relative to normal brain. Body weight monitoring indicated no significant treatment-related toxicity. Conclusion BNCT demonstrated therapeutic efficacy and feasibility in a preclinical model of multiple brain metastases, providing a survival benefit without excessive toxicity. These findings support further investigation of BNCT as a potential treatment strategy for multifocal intracranial disease.

Accurate evaluation of neutron leakage dose plays a critical role in radiation protection for accelerator-based boron neutron capture therapy (AB-BNCT). This study reports the experimental validation of a neutron detector system for direct measurement of the neutron ambient dose, H*, in AB-BNCT irradiation fields. The system comprises an S-detector for detecting low-energy neutrons and an F-detector for higher-energy neutrons, with sensitivity extending up to 28 MeV. Detector geometries were optimized using Monte Carlo simulations to reproduce the fluence-to-H* conversion coefficients recommended in the ICRP Publication 116. Prototype detectors were tested in standard neutron fields, including thermal, monoenergetic, and fast neutron sources. The measured detector responses agreed well with calculated values, with deviations ranging from −13% to +4% for response and from −25% to −2% for dose response relative to ICRP values. These results demonstrate the suitability of the developed detector system for evaluating ambient neutron dose in AB-BNCT environments.

Boron neutron capture therapy (BNCT) dose calculation often relies on fixed relative biological effectiveness (RBE) and compound biological effectiveness (CBE) values, despite their dependence on beam quality and tumor biology. We developed a microdosimetry-driven framework that predicts cell survival and RBE for BNCT by coupling PHITS lineal energy (T-SED) calculations with the microdosimetric kinetic (MK) model. MK parameters ( α ₀ , β , r _d , y ₀ ) were derived for BNCT relevant cell lines (U87 glioblastoma, NB1RG skin fibroblasts, SAS human squamous carcinoma, and SCC7 murine squamous carcinoma) using low-LET reference datasets curated in the PIDE database and irradiation conditions reproduced in PHITS. The derived parameters successfully reproduced in vitro survival curves for various charged particles across different energies, and when applied to neutron fields representative of BNCT systems (Kyoto University Reactor thermal neutron beam, cyclotron-based epithermal neutron source using a beryllium target, and linear accelerator system using a lithium target), the framework also reproduced measured in vitro data. Predicted RBE at 10% survival (RBE ₁₀ ) agreed with measurements across cell lines and beam qualities, with only a slight deviation for SCC7 under the CICS spectrum and moderate deviations for SAS due to limited and heterogeneous low-LET datasets in PIDE. This method enables spectrum and cell-line specific estimation of biological effect, supporting replacement of fixed RBE/CBE with spectrum aware quantities to improve BNCT dose prescription and safety. The framework can also guide neutron-beam design by providing preliminary RBE estimates prior to construction of the moderator and beam shaping assembly. Incorporating intracellular boron microdistribution in future work is expected to refine CBE estimates and enhance biological accuracy in BNCT treatment planning. This framework provides a physics-based alternative to fixed RBE/CBE values.

The Boron Neutron Capture Therapy (BNCT) irradiation field comprises high-intensity neutrons and gamma-rays that need to be measured separately because of their different biological effects. To conduct appropriate quality assurance (QA), we should measure the neutrons and gamma-rays. In a previous study, an air-ionization chamber combined with a fiber-type neutron monitor was constructed for QA. However, the fibers attached to the chamber were perturbed by neutron scattering. To eliminate the effect of perturbations, we developed an air ionization chamber into which the fiber could be inserted. Irradiation tests in the BNCT irradiation field showed that the perturbation effect was reduced by less than half, and it was confirmed that the system could measure neutrons and gamma-rays simultaneously for weekly QA. The sensitivity of the chamber to neutron energy was evaluated via simulations, and it was found that corrections for sensitivity to high-energy neutrons are required.