Abstract
AB015. Efficacy and safety of boron neutron capture therapy in managing metastatic spinal tumors: experimental findings
Yoshiki Fujikawa1, Shinji Kawabata1, Kohei Tsujino1, Hironori Yamada1, Hideki Kashiwagi1, Ryo Hiramatsu1, Takushi Takata2, Hiroki Tanaka2, Minoru Suzuki2, Naonori Hu3, Shin-Ichi Miyatake3, Toshihiro Takami1, Masahiko Wanibuchi1
1Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Takatsuki, Japan;
2Institute for Integrated Radiation and Nuclear Science, Kyoto University, Kyoto, Japan;
3Kansai BNCT Center, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
Correspondence to: Yoshiki Fujikawa, MD. Department of Neurosurgery, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-cho, Takatsuki, Osaka, Japan. Email: yoshiki.fujikawa@ompu.ac.jp.
Background: Boron neutron capture therapy (BNCT) is a unique cancer treatment modality that enables precise targeting of tumors at the cellular level. Based on the success observed in nuclear reactors, BNCT now holds promise as a therapeutic approach for treating invasive brain tumors or head and neck cancers. Metastatic spinal tumors have been treated with multidisciplinary interventions such as surgical resection and radiation therapy. Despite recent advantages of radiation therapy, it remains challenging to achieve better quality of life and activity of daily living. The purpose of this study was to evaluate the efficacy and safety of BNCT in metastatic spinal tumor using a mouse model.
Methods: For the in vitro, neutron and photon irradiation was applied to A549 human lung adenocarcinoma cells. The cells were irradiated neutrons with or without p-boronophenylalanine (BPA) 10 µg Boron/mL for a 24-h exposure before neutron irradiation. The difference of biological effect between neutrons and photons was evaluated by colony forming assay. For in vivo, the tumor-bearing mice were intravenously administered BPA (250 mg/kg), followed by measuring biodistribution of boron using inductively coupled plasma atomic emission spectroscopy (ICP-AES). For in vivo BNCT, the mice were randomly assigned to untreated (n=10), neutron irradiation only (n=9), and BNCT groups (n=10). Overall survival and hindlimb function were analyzed. Histopathological examination was also performed to assess the influences of neutron irradiation.
Results: Neutron irradiation showed a stronger cell-killing effect than that exhibited by photon irradiation in vitro. For in vivo biodistribution, the highest boron accumulation in the tumor was seen at 2.5-h time point (10.5 µg B/g), with a tumor to normal spinal cord and blood ratios were 3.6 and 2.9, respectively. For the in vivo BNCT, BNCT had significantly prolonged survival (vs. untreated, P=0.002; vs. neutron only, P=0.01, respectively, log-rank test) and preserved mice hindlimb function compared to the other groups (vs. untreated, P<0.001; vs. neutron only, P=0.005, respectively, MANOVA). No adverse events and apparent histopathological changes were observed among three groups.
Conclusions: These findings indicate that BNCT may represent a novel therapeutic option in the management of metastatic spinal tumors.
Keywords: Boron neutron capture therapy (BNCT); metastatic spinal tumor; spinal cord compression
Acknowledgments
Funding: This research was funded by the Japan Society for the Promotion of Science (JSPS) KAKENHI (No. JP22K09270 to Toshihiro Takami) (Grants-in-Aid for Science Research [C]) and partly by the Japan Society for the Promotion of Science (JSPS) KAKENHI (No. JP23H03024 to S.K.) (Grants-in-Aid for Science Research [B]).
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cco.amegroups.com/article/view/10.21037/cco-24-ab015/coif). Toshihiro Takami reported funding for this research from the Japan Society for the Promotion of Science (JSPS) KAKENHI (No. JP22K09270). S.K. also reported funding for this research from the Japan Society for the Promotion of Science (JSPS) KAKENHI (No. JP23H03024). The other authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and approved by the Ethical Committee of Osaka Medical and Pharmaceutical University (No. AM2023-019) and Kyoto University Institute for Integrated Radiation and Nuclear Science (No. R5031) and informed consent was obtained from all individual participants.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
Cite this abstract as: Fujikawa Y, Kawabata S, Tsujino K, Yamada H, Kashiwagi H, Hiramatsu R, Takata T, Tanaka H, Suzuki M, Hu N, Miyatake SI, Takami T, Wanibuchi M. AB015. Efficacy and safety of boron neutron capture therapy in managing metastatic spinal tumors: experimental findings. Chin Clin Oncol 2024;13(Suppl 1):AB015. doi: 10.21037/cco-24-ab015
