[Background] Boron neutron capture therapy (BNCT) is a particle beam therapy that enables the precise targeting of tumors at the cellular level. Building on the success observed in nuclear reactors, BNCT exhibits potential as a therapeutic approach for managing invasive brain tumors, including malignant gliomas and high-grade meningiomas. Metastatic spinal tumors have been treated by surgical removal, radiation therapy, and a variety of other multidisciplinary therapies. However, none of them has been successful in overcoming this metastatic disease. This study aimed to assess the efficacy of BNCT in treating metastatic spinal tumor using a mouse model.
[Methods] In vitro experiment: neutron irradiation was applied to A549 human lung carcinoma cells with (BNCT group) or without p-boronophenylalanine (BPA) 10 µg Boron/mL for 24 h exposure before irradiation (hot control group) for 0 to 30 min. The cell killing effect was assessed by a colony forming assay. In vivo experiment: an A549 subcutaneous tumor was removed and implanted into the lumbar lamina, where it was partially resected. A few weeks later, metastatic spinal tumor models were successfully established. For the biodistribution of boron, after 2.5, 6, or 24 h of intravenous BPA administration (250 mg/mouse body weight), the metastatic spinal tumor models were sacrificed and the boron concentration of the tumor and each organ measured using Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES).
[Results] In vitro neutron experiment: the BNCT group showed a greater cell killing effect than the hot control group. The highest boron accumulation in the tumor was observed at 2.5 h after BPA administration (10.5 µg B/g), and the tumor to normal spinal cord ratio (T/N) was 3.6 and the tumor to blood ratio (T/Bl) was 2.9.
[Conclusions] The findings may indicate that BNCT represents an effective approach in the management of metastatic spinal tumor. We will perform an in vivo neutron irradiation experiment on this model to evaluate the effects of BNCT on survival and neurological function.
Author Contributions
Conceptualization, S.K.; methodology, Y.F. (Yoshiki Fujikawa), K.T., R.K., H.K., Y.F. (Yusuke Fukuo), R.H. and S.K.; validation, Y.F. (Yoshiki Fujikawa) and S.K.; formal analysis, Y.F. (Yoshiki Fujikawa); investigation, Y.F. (Yoshiki Fujikawa); resources, T.T. (Takushi Takata), H.T., N.H. and M.S.; data curation, Y.F. (Yoshiki Fujikawa); writing—original draft preparation, Y.F. (Yoshiki Fujikawa); writing—review and editing, S.K.; visualization, Y.F. (Yoshiki Fujikawa); supervision, S.-I.M. and M.W.; project administration, S.K.; funding acquisition, S.K. and T.T. (Toshihiro Takami). All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by the Japan Society for the Promotion of Science (JSPS) KAKENHI, grant number JP22K09270 to T.T. (Toshihiro.Takami) [Grants-in-Aid for Science Research (C)] and partly by JP23H03024 to S.K. [Grants-in-Aid for Science Research (B)].
Institutional Review Board Statement
The study was conducted in accordance with the guidelines of the Declaration of Helsinki and approved by the Animal Use Review Board and Ethical Committee of Osaka Medical and Pharmaceutical University (No. AM2023-019) and the Institute for Integrated Radiation and Nuclear Science, Kyoto University (No. R5032).
Informed Consent Statement
Not applicable.
Data Availability Statement
All data analyzed in this study are available upon reasonable request to the corresponding author. The JMP Pro version 16.2.0. software (SAS, Cary, NC, USA) was used for the statistical analysis.
Conflicts of Interest
The authors declare no conflicts of interest.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).