Chordoma Treatment with Boron Neutron Capture Therapy (BNCT): Experimental Insights

first_page Download PDF settings Order Article Reprints Font Type: Arial Georgia Verdana Font Size: Aa Aa Aa Line Spacing:    Column Width:    Background: Open AccessAbstract Chordoma Treatment with Boron Neutron Capture Therapy (BNCT): Experimental Insights † by Yoshiki FujikawaYoshiki Fujikawa SciProfiles Scilit Preprints.org Google Scholar 1,*, Shinji KawabataShinji Kawabata SciProfiles Scilit Preprints.org Google Scholar 1, Kohei TsujinoKohei Tsujino SciProfiles Scilit Preprints.org Google Scholar 1, Hideki KashiwagiHideki Kashiwagi SciProfiles Scilit Preprints.org Google Scholar 1, Yusuke FukuoYusuke Fukuo SciProfiles Scilit Preprints.org Google Scholar 1, Ryo HiramatsuRyo Hiramatsu SciProfiles Scilit Preprints.org Google Scholar 1, Hiroki TanakaHiroki Tanaka SciProfiles Scilit Preprints.org Google Scholar 2, Naonori HuNaonori Hu SciProfiles Scilit Preprints.org Google Scholar 3, Toshihiro TakamiToshihiro Takami SciProfiles Scilit Preprints.org Google Scholar 1 and Masahiko WanibuchiMasahiko Wanibuchi SciProfiles Scilit Preprints.org Google Scholar 1 1 Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan 2 Institute for Integrated Radiation and Nuclear Science, Kyoto University, Kumatori 520-2113, Japan 3 Kansai BNCT Medical Center, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan * Author to whom correspondence should be addressed. † Presented at the 4th International Electronic Conference on Cancers, 6–8 March 2024; Available online: https://sciforum.net/event/IECC2024. Proceedings 2024, 100(1), 13; https://doi.org/10.3390/proceedings2024100013 Published: 27 March 2024 Download keyboard_arrow_down Download PDF Download PDF with Cover Download XML Download Epub Versions Notes Keywords: Boron Neutron Capture Therapy (BNCT); biodistribution of boron; cell-killing effect; chordoma; in vitro and in vivo experiments; radiation therapy 1. BackgroundBoron Neutron Capture Therapy (BNCT) is a particle beam therapy that enables the precise targeting of tumors at the cellular level. Drawing on the success observed in nuclear reactors, BNCT holds promise as a therapeutic approach for addressing invasive brain tumors, such as malignant gliomas and high-grade meningiomas.Chordomas are rare bone tumors characterized by locally invasive, frequent recurrence, and relative radioresistance. Recently, treatment modalities, including proton or carbon ions particle irradiation, have been developed; however, conclusive evidence supporting their efficacy is yet to be established. This experimental study aimed to evaluate the effectiveness of BNCT in the treatment of chordoma. 2. MethodsThe U-CH1 and JHC7 human chordoma cell lines were employed in this study. In the in vitro experiment, both cell lines were exposed to p-boronophenylalanine (BPA) at a concentration of 10 µg boron/mL for duration of 3, 6, and 24 h. Subsequently, the measurement of cellular boron uptake was conducted using Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES). After 24 h of exposure, the medium was replaced with a boron-free medium, and the subsequent investigation was focused on boron clearance. Neutron irradiation was then applied to these two cell lines, BNCT with BPA (10 µg Boron/mL for a 24-h exposure before irradiation) (BNCT group), and neutron irradiation without BPA (hot control group), for 0 to 30 min. Assessment of the cell-killing effect was carried out using a colony forming assay. In the in vivo experiment, subcutaneous tumor-bearing mice were intravenously administered BPA (250 mg/mouse body weight). After 1 h, the mice were sacrificed, and the boron concentrations in both the tumor and each organ were measured using ICP-AES. 3. ResultsIn the in vitro BPA exposure experiment, U-CH1 exhibited an increase in cellular boron uptake with prolonged BPA exposure time, whereas JHC7 demonstrated a consistent uptake unaffected by exposure time. Both cell lines showed a rapid decrease in cellular boron concentration after incubation with boron-free medium. Neutron irradiation revealed that the BNCT group demonstrated a more pronounced cell-killing effect than the hot control group in both cell lines. In the in vivo biodistribution of boron, the tumor accumulation was 5.7 µg B/g with a tumor-to-blood ratio (T/Bl) of 1.3 in U-CH1, while JHC7 showed a tumor accumulation of 9.3 µg B/g, with a T/Bl of 1.5. 4. ConclusionsDespite the relatively low intracellular boron uptake compared to other malignant tumors, these findings suggest that BNCT may represent an effective approach in the management of chordoma. Future efforts will include in vivo neutron irradiation experiments to more fully assess the effects of BNCT on survival and neurological function. Author ContributionsConceptualization, S.K.; methodology, Y.F. (Yoshiki Fujikawa), K.T., 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, H.T., and N.H.; 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, M.W.; project administration, S.K.; funding acquisition, S.K and T.T. All authors have read and agreed to the published version of the manuscript.FundingThis research was funded by the Japan Society for the Promotion of Science (JSPS) KAKENHI, grant number JP22K09270 to T.T. [Grants-in-Aid for Science Research (C)] and partly by JP23H03024 to S.K. [Grants-in-Aid for Science Research (B)].Institutional Review Board StatementThe 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. R5031).Informed Consent StatementNot applicable.Data Availability StatementAll 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 InterestThe 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/). Share and Cite MDPI and ACS Style Fujikawa, Y.; Kawabata, S.; Tsujino, K.; Kashiwagi, H.; Fukuo, Y.; Hiramatsu, R.; Tanaka, H.; Hu, N.; Takami, T.; Wanibuchi, M. Chordoma Treatment with Boron Neutron Capture Therapy (BNCT): Experimental Insights. Proceedings 2024, 100, 13. https://doi.org/10.3390/proceedings2024100013 AMA Style Fujikawa Y, Kawabata S, Tsujino K, Kashiwagi H, Fukuo Y, Hiramatsu R, Tanaka H, Hu N, Takami T, Wanibuchi M. Chordoma Treatment with Boron Neutron Capture Therapy (BNCT): Experimental Insights. Proceedings. 2024; 100(1):13. https://doi.org/10.3390/proceedings2024100013 Chicago/Turabian Style Fujikawa, Yoshiki, Shinji Kawabata, Kohei Tsujino, Hideki Kashiwagi, Yusuke Fukuo, Ryo Hiramatsu, Hiroki Tanaka, Naonori Hu, Toshihiro Takami, and Masahiko Wanibuchi. 2024. "Chordoma Treatment with Boron Neutron Capture Therapy (BNCT): Experimental Insights" Proceedings 100, no. 1: 13. https://doi.org/10.3390/proceedings2024100013 Article Metrics No No Article Access Statistics Multiple requests from the same IP address are counted as one view.