Recently, exploitation of cerebrospinal fluid (CSF) circulation has become increasingly recognized as a feasible strategy to solve the challenges involved in drug delivery for treating brain tumors. Boron neutron capture therapy (BNCT) also faces challenges associated with the development of an efficient delivery system for boron, especially to brain tumors. Our laboratory has been developing a system for boron delivery to brain cells using CSF, which we call the “boron CSF administration method”. In our previous study, we found that boron was efficiently delivered to the brain cells of normal rats in the form of small amounts of L-p-boronophenylalanine (BPA) using the CSF administration method. In the study described here, we carried out experiments with brain tumor model rats to demonstrate the usefulness of the CSF administration method for BNCT. We first investigated the boron concentration of the brain cells every 60 min after BPA administration into the lateral ventricle of normal rats. Second, we measured and compared the boron concentration in the melanoma model rats after administering boron via either the CSF administration method or the intravenous (IV) administration method, with estimation of the T/N ratio. Our results revealed that boron injected by the CSF administration method was excreted quickly from normal cells, resulting in a high T/N ratio compared to that of IV administration. In addition, the CSF administration method resulted in high boron accumulation in tumor cells. In conclusion, we found that using our developed CSF administration method results in more selective delivery of boron to the brain tumor compared with the IV administration method.

Boron neutron capture therapy (BNCT) is a non-invasive type of radiation therapy developed for humans and translated to veterinary medicine. However, clinical trials on BNCT for patients with brain tumors are on-going. To improve the therapeutic efficacy of BNCT for brain tumors, we developed a boron delivery system that involves the cerebrospinal fluid (CSF), in contrast to the conventional method that involves intravenous (IV) administration. This study aimed to investigate the time-concentration profile of boron in the CSF as well as the uptake rate of boron by the brain cells after administering L-p‑boronophenylalanine (BPA) into the lateral ventricle of normal rats. Brain cell uptake rates were compared between the CSF-based and IV administration methods. The CSF-based and IV administration methods achieved comparable brain cell uptake levels; however, the former method involved lower BPA doses than the latter method. These findings suggest that the CSF method may reduce the economic and physical burdens associated with this treatment in brain tumor patients. Future studies should validate these findings in rat models of brain tumors.

At 14 MeV, it is known that the absolute value of large angle scattering cross section is small. The contribution is thus thought to be neglected in the neutronics design of fusion reactor. However, in case that a neutron source can be regarded as a beam like a neutron streaming, large angle scattering cross sections might affect the nuclear design result largely. In fact, in fusion neutronics benchmark experiments using a neutron beam so far, there was a difference observed between experiment and simulation. Also it is known that there are differences in large angle scattering cross sections among nuclear data libraries. Then we have been carrying out preliminary benchmark experiments for verification of large angle scattering reaction cross sections of iron for a few years. The purpose of the present study is to optimize the experimental system design to realize an accurate benchmarking of large angle scattering reaction cross sections. Finally, we reached the optimized experimental system and developed the experimental procedure which was supposed to perform more accurate benchmark experiments for large angle scattering reaction cross sections.

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.