Boron neutron capture therapy (BNCT) is a unique anticancer technology that has demonstrated its efficacy in numerous phase I/II clinical trials with boronophenylalanine (BPA) and sodium borocaptate (BSH) used as ¹⁰B delivery agents. However, continuous drug administration at high concentrations is needed to maintain sufficient ¹⁰B concentration within tumors. To address the issue of ¹⁰B accumulation and retention in tumor tissue, we developed MMT1242, a novel boron-containing α-d-mannopyranoside. We evaluated the uptake, intracellular distribution, and retention of MMT1242 in cultured cells and analyzed biodistribution, tumor-to-normal tissue ratio and toxicity in vivo. Fluorescence imaging using nitrobenzoxadiazole (NBD)-labeled MMT1242 and inductively coupled mass spectrometry (ICP-MS) were performed. The effectiveness of BNCT using MMT1242 was assessed in animal irradiation studies at the Kyoto University Research Reactor. MMT1242 showed a high uptake and broad intracellular distribution in vitro, longer tumor retention compared to BSH and BPA, and adequate tumor-to-normal tissue accumulation ratio and low toxicity in vivo. A neutron irradiation study with MMT1242 in a subcutaneous murine tumor model revealed a significant tumor inhibiting effect if injected 24 h before irradiation. We therefore report that ¹⁰B-MMT1242 is a candidate for further clinical BNCT studies.

Boron neutron capture therapy (BNCT) has been performed at nuclear research reactors for many years. The development of accelerators for BNCT resulted in a paradigm shift from research to real clinical applications. In Japan, BNCT was approved as a clinical therapy covered by the National Health Insurance in 2020. In this article, the status of BNCT in Japan is briefly introduced.

Purpose: To evaluate the efficacy of boron neutron capture therapy (BNCT) for a heterotopic U87 glioblastoma model in SCID mice using boron phenylalanine (BPA), sodium borocaptate (BSH) and liposomal BSH as boron compounds at a unique, accelerator-based neutron source. Materials and methods: Glioblastoma models were obtained by subcutaneous implantation of U87 cells in the right thighs of SCID mice before administration of 350 mg/kg of BPA (BPA-group), 100 mg/kg of BSH (BSH-group) or 100 mg/kg of BSH in PEGylated liposomes (liposomal BSH-group) into the retroorbital sinus. Liposomes were prepared by reverse-phase evaporation. Neutron irradiation was carried out at a proton accelerator with a lithium target developed for BNCT at the Budker Institute of Nuclear Physics, Novosibirsk, Russian Federation. A proton beam current integral of 3 mA/hour and energy of 2.05 MeV were used for neutron generation. Results: Boron compound accumulation in tumor tissues at the beginning of irradiation was higher in the BPA group, followed by the Liposomal BSH and BSH groups. Tumor growth was significantly slower in all irradiated mice from the 7^th day after BNCT compared to untreated controls (p < 0.05). Tumor growth in all treated groups showed no large variation, apart from the Irradiation only group and the BPA group on the 7^th day after BNCT. The overall trend of tumor growth was clear and the differences between treatment groups became significant from the 50^th day after BNCT. Tumor growth was significantly slower in the Liposomal BSH group compared to the Irradiation only group on the 50^th (p = 0.012), 53^rd (p = 0.005), and the 57^th (p = 0.021) days after treatment. Tumor growth in the Liposomal BSH group was significantly different from that in the BPA group on the 53^rd day after BNCT (p = 0.021) and in the BSH group on the 50^th (p = 0.024), 53^rd (p = 0.015), and 57^th (p = 0.038) days after BNCT. Skin reactions in the form of erosions and ulcers in the tumor area developed in treated as well as untreated animals with further formation of fistulas and necrotic decay cavities in most irradiated mice. Conclusions: We observed a tendency of BNCT at the accelerator-based neutron source to reduce or suspend the growth of human glioblastoma in immunodeficient animals. Liposomal BSH showed better long-term results compared to BPA and non-liposomal BSH. Further modifications in liposomal boron delivery are being studied to improve treatment outcomes.

In clinical practice, acute post-stroke paresis of the extremities fundamentally complicates timely rehabilitation of motor functions; however, recently, residual and distorted musculoskeletal signals have been used to initiate feedback-driven solutions for establishing motor rehabilitation. Here, we investigate the possibilities of basic hand gesture recognition in acute stroke patients with hand paresis using a novel, acute stroke, four-component multidomain feature set (ASF-4) with feature vector weight additions (ASF-14NP, ASF-24P) and supervised learning algorithms trained only by surface electromyography (sEMG). A total of 19 (65.9 ± 12.4 years old; 12 men, seven women) acute stroke survivors (12.4 ± 6.3 days since onset) with hand paresis (Brunnstrom stage 4 ± 1/4 ± 1, SIAS 3 ± 1/3 ± 2, FMA-UE 40 ± 20) performed 10 repetitive hand movements reflecting basic activities of daily living (ADLs): rest, fist, pinch, wrist flexion, wrist extension, finger spread, and thumb up. Signals were recorded using an eight-channel, portable sEMG device with electrode placement on the forearms and thenar areas of both limbs (four sensors on each extremity). Using data preprocessing, semi-automatic segmentation, and a set of extracted feature vectors, support vector machine (SVM), linear discriminant analysis (LDA), and k-nearest neighbors (k-NN) classifiers for statistical comparison and validity (paired t-tests, p-value < 0.05), we were able to discriminate myoelectrical patterns for each gesture on both paretic and non-paretic sides. Despite any post-stroke conditions, the evaluated total accuracy rate by the 10-fold cross-validation using SVM among four-, five-, six-, and seven-gesture models were 96.62%, 94.20%, 94.45%, and 95.57% for non-paretic and 90.37%, 88.48%, 88.60%, and 89.75% for paretic limbs, respectively. LDA had competitive results using PCA whereas k-NN was a less efficient classifier in gesture prediction. Thus, we demonstrate partial efficacy of the combination of sEMG and supervised learning for upper-limb rehabilitation procedures for early acute stroke motor recovery and various treatment applications.

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.

Glioblastoma (GBM) is difficult to cure with conventional multimodal treatment and has an extremely poor prognosis. Boron neutron capture therapy (BNCT) is a new particle therapy for malignant tumors in the brain and head and neck region. This radiotherapy utilizes a nuclear reaction between neutrons and a nonradioactive isotope, boron-10. In this method, a boron compound is administered transvenously into the body. The boron compound has the property of being selectively taken up only by the cells of malignant tumors, and the subsequent irradiation with neutrons can destroy malignant tumor cells without damaging normal cells. Since the irradiation dose to normal tissues is reduced in BNCT, it may be possible to re-irradiate malignant tumors that recur after radiotherapy. Clinical trials have reported prolonged survival and safety of BNCT in a small number of patients with refractory malignancies, including GBM, but these reports do not address quality of life or activities of daily living (ADL) after treatment, and there is no information on the assessment of local control by imaging. Here, we report a case of GBM that recurred after surgery, 60 Gy of conventional radiotherapy and standard treatment with temozolomide. The patient achieved long-term local control and survival over five years after BNCT and was able to maintain ADL at home without any specialist care. We describe the case with evaluation using longitudinal magnetic resonance imaging (MRI).