Accelerator neutron sources for BNCT: Current status and some pointers for future development.

Recent decades have seen the development of accelerator neutron sources suitable for installation in a hospital setting. Numerous challenges have been faced and solved to deliver technology which continues to transform the field of BNCT. This paper begins by briefly reviewing the technologies which are currently, or soon will be, in clinical use.

Evaluation of dose calculation method with a combination of Monte Carlo method and removal-diffusion equation in heterogeneous geometry for boron neutron capture therapy.

Clinical research in boron neutron capture therapy (BNCT) has been conducted worldwide. Currently, the Monte Carlo (MC) method is the only dose calculation algorithm implemented in the treatment planning system for the clinical treatment of BNCT. We previously developed the MC-RD calculation method, which combines the MC method and the removal-diffusion (RD) equation, for fast dose calculation in BNCT.

Characterization of acrylic phantom for use in quality assurance of BNCT beam output procedure.

The accelerator-based boron neutron capture therapy (BNCT) system has been approved for specific cases covered by health insurance, and clinical trials for new cases in Japan are currently being conducted on other systems. Owing to the progress of accelerator-based BNCT, the operation of medical physics must be rendered more efficient. A water phantom is used for the quality assurance (QA) of the BNCT beam output procedure; however, a solid phantom is preferred for routine QA because of its ease of use.

Implementation of optically simulated luminescent dosimeter for quality control of gamma ray dose of an accelerator-based neutron source.

Background: Neutron beams utilized for performing BNCT are composed of a mixture of neutrons and gamma rays. Although much of the dose delivered to the cancer cells comes from the high LET particles produced by the boron neutron capture reaction, the dose delivered to the healthy tissues from unwanted gamma rays cannot be ignored. With the increase in the number of accelerators for BNCT, a detector system that is capable of measuring gamma ray dose in a mixed neutron/gamma irradiation field is crucial.

Preliminary outcomes of boron neutron capture therapy for head and neck cancers as a treatment covered by public health insurance system in Japan: Real-world experiences over a 2-year period.

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.

Nonclinical pharmacodynamics of boron neutron capture therapy using direct intratumoral administration of a folate receptor targeting novel boron carrier.

Background: Boron neutron capture therapy (BNCT) is a precise particle radiation therapy known for its unique cellular targeting ability. The development of innovative boron carriers is crucial for the advancement of BNCT technologies. Our previous study demonstrated the potential of PBC-IP administered via convection-enhanced delivery (CED) in an F98 rat glioma model.

Application of stoichiometric CT number calibration method for dose calculation of tissue heterogeneous volumes in boron neutron capture therapy.

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.

Translational research of boron neutron capture therapy for spinal cord gliomas using rat model.

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.

Neutron flux evaluation algorithm with a combination of Monte Carlo and removal-diffusion calculation methods for boron neutron capture therapy.

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.

Out-of-field dosimetry using a validated PHITS model and computational phantom in clinical BNCT.

Background: The out-of-field radiation dose for boron neutron capture therapy (BNCT), which results from both neutrons and γ-rays, has not been extensively evaluated. To safely perform BNCT, the neutron and γ-ray distributions inside the treatment room and the whole-body dose should be evaluated during commissioning. Although, certain previous studies have evaluated the whole-body dose in the clinical research phase, no institution providing BNCT covered by health insurance has yet validated the neutron distribution inside the room and the whole-body dose.

Evaluation of the Effectiveness of Boron Neutron Capture Therapy with Iodophenyl-Conjugated -Dodecaborate on a Rat Brain Tumor Model.

High-grade gliomas present a significant challenge in neuro-oncology because of their aggressive nature and resistance to current therapies. Boron neutron capture therapy (BNCT) is a potential treatment method; however, the boron used by the carrier compounds-such as 4-borono-L-phenylalanine (L-BPA)-have limitations. This study evaluated the use of boron-conjugated 4-iodophenylbutanamide (BC-IP), a novel boron compound in BNCT, for the treatment of glioma.

Proposal of recommended experimental protocols for in vitro and in vivo evaluation methods of boron agents for neutron capture therapy.

Recently, boron neutron capture therapy (BNCT) has been attracting attention as a minimally invasive cancer treatment. In 2020, the accelerator-based BNCT with L-BPA (Borofalan) as its D-sorbitol complex (Steboronine®) for head and neck cancers was approved by Pharmaceutical and Medical Devices Agency for the first time in the world. As accelerator-based neutron generation techniques are being developed in various countries, the development of novel tumor-selective boron agents is becoming increasingly important and desired.

Feasibility study of optical imaging of the boron-dose distribution by a liquid scintillator in a clinical boron neutron capture therapy field.

Background: Evaluation of the boron dose is essential for boron neutron capture therapy (BNCT). Nevertheless, a direct evaluation method for the boron-dose distribution has not yet been established in the clinical BNCT field. To date, even in quality assurance (QA) measurements, the boron dose has been indirectly evaluated from the thermal neutron flux measured using the activation method with gold foil or wire and an assumed boron concentration in the QA procedure.

Optimizing Boron Neutron Capture Therapy (BNCT) to Treat Cancer: An Updated Review on the Latest Developments on Boron Compounds and Strategies.

Boron neutron capture therapy (BNCT) is a tumor-selective particle radiotherapy. It combines preferential boron accumulation in tumors and neutron irradiation. The recent initiation of BNCT clinical trials employing hospital-based accelerators rather than nuclear reactors as the neutron source will conceivably pave the way for new and more numerous clinical trials, leading up to much-needed randomized trials.

Experimentally determined relative biological effectiveness of cyclotron-based epithermal neutrons designed for clinical BNCT: in vitro study.

A neutron beam for boron neutron capture therapy (BNCT) of deep-seated tumours is designed to maintain a high flux of epithermal neutrons, while keeping the thermal and fast neutron component as low as possible. These neutrons (thermal and fast) have a high relative biological effectiveness in comparison with high energy photon beams used for conventional X-ray radiotherapy. In the past, neutrons for the purpose of BNCT were generated using nuclear reactors.

Development of optimization method for uniform dose distribution on superficial tumor in an accelerator-based boron neutron capture therapy system.

To treat superficial tumors using accelerator-based boron neutron capture therapy (ABBNCT), a technique was investigated, based on which, a single-neutron modulator was placed inside a collimator and was irradiated with thermal neutrons. In large tumors, the dose was reduced at their edges. The objective was to generate a uniform and therapeutic intensity dose distribution.

Development and evaluation of dose calculation algorithm with a combination of Monte Carlo and point-kernel methods for boron neutron capture therapy.

We developed a 'hybrid algorithm' that combines the Monte Carlo (MC) and point-kernel methods for fast dose calculation in boron neutron capture therapy. The objectives of this study were to experimentally verify the hybrid algorithm and to verify the calculation accuracy and time of a 'complementary approach' adopting both the hybrid algorithm and the full-energy MC method. In the latter verification, the results were compared with those obtained using the full-energy MC method alone.

Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model.

Integrin αβ is more highly expressed in high-grade glioma cells than in normal tissues. In this study, a novel boron-10 carrier containing maleimide-functionalized -dodecaborate (MID), serum albumin as a drug delivery system, and cyclic arginine-glycine-aspartate (cRGD) that can target integrin αβ was developed. The efficacy of boron neutron capture therapy (BNCT) targeting integrin αβ in glioma cells in the brain of rats using a cRGD-functionalized MID-albumin conjugate (cRGD-MID-AC) was evaluated.

Multi-Targeted Neutron Capture Therapy Combined with an 18 kDa Translocator Protein-Targeted Boron Compound Is an Effective Strategy in a Rat Brain Tumor Model.

Background: Boron neutron capture therapy (BNCT) has been adapted to high-grade gliomas (HG); however, some gliomas are refractory to BNCT using boronophenylalanine (BPA). In this study, the feasibility of BNCT targeting the 18 kDa translocator protein (TSPO) expressed in glioblastoma and surrounding environmental cells was investigated.

Methods: Three rat glioma cell lines, an F98 rat glioma bearing brain tumor model, DPA-BSTPG which is a boron-10 compound targeting TSPO, BPA, and sodium borocaptate (BSH) were used.

Exploration of the threshold SUV for diagnosis of malignancy using F-FBPA PET/CT.

Background: The goal of the study was to evaluate the diagnostic ability of F-FBPA PET/CT for malignant tumors. Findings from F-FBPA and F-FDG PET/CT were compared with pathological diagnoses in patients with malignant tumors or benign lesions.

Methods: A total of 82 patients (45 males, 37 females; median age, 63 years; age range, 20-89 years) with various types of malignant tumors or benign lesions, such as inflammation and granulomas, were examined by F-FDG and F-FBPA PET/CT.

Intensity-modulated irradiation for superficial tumors by overlapping irradiation fields using intensity modulators in accelerator-based BNCT.

The distribution of the thermal neutron flux has a significant impact on the treatment efficacy. We developed an irradiation method of overlapping irradiation fields using intensity modulators for the treatment of superficial tumors with the aim of expanding the indications for accelerator-based boron neutron capture therapy (BNCT). The shape of the intensity modulator was determined and Monte Carlo simulations were carried out to determine the uniformity of the resulting thermal neutron flux distribution.

Improvement in the neutron beam collimation for application in boron neutron capture therapy of the head and neck region.

In June 2020, the Japanese government approved boron neutron capture therapy for the treatment of head and neck cancer. The treatment is usually performed in a single fraction, with the neutron irradiation time being approximately 30-60 min. As neutrons scatter in air and loses its intensity, it is preferable to bring the patient as close to the beam port as possible to shorten the irradiation time.