Abstract
AB027. Exploratory study to expand the indication of boron neutron capture therapy based on LAT1 expression in tumors
Tsubasa Watanabe1,2, Yu Sanada1, Yoshihide Hattori3, Minoru Suzuki1
1Institute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka, Japan;
2The Hakubi Project, Kyoto University, Kyoto, Japan;
3Research Center for Boron Neutron Capture Therapy, Osaka Metropolitan University, Osaka, Japan
Correspondence to: Tsubasa Watanabe, MD, PhD. Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan; The Hakubi Project, Kyoto University, Kyoto, Japan. Email: watanabe.tsubasa.8x@kyoto-u.ac.jp.
Background: The indication for boron neutron capture therapy (BNCT) in the Japanese insurance system is currently unresectable locally advanced or locally recurrent head and neck cancer. One of the challenges of BNCT research now is to expand indications to various types of tumors. It is desirable to develop a method for predicting the therapeutic effect of this therapy and a guideline for determining whether the therapy is indicated or not. In this study, we focused on the amino acid transporter LAT1 molecule and evaluated the relationship between LAT1 expression in tumor cells and accumulation of the boron drug boronophenylalanine (BPA) to determine whether LAT1 expression level in the tumor cells is a useful marker for assessing BPA uptake and evaluating the indication for BNCT in the future.
Methods: We quantitatively evaluated BPA uptake in tumor cells squamous cell carcinoma (SCC)-VII with suppressed and strongly expressed LAT1 using CRISPR/Cas9, and compared it to conditions with LAT1 inhibitors using inductively coupled plasma atomic emission spectroscopy (ICP-AES) and flow cytometry. The Cancer Genome Atlas (TCGA) database was used to examine the association between LAT1 expression and the primary site and histology of human tumors.
Results: BPA accumulation in cells with strong LAT1 expression was about 1.5-fold higher than that in the target group, and BPA accumulation in cells with attenuated LAT1 expression was comparable to that in cells with LAT1 inhibitor, confirming that the accumulation of BPA in tumor cells is highly dependent on LAT1 expression in tumor cells. Analysis of the TCGA database analyses showed that SCC in particular tended to have higher expression of LAT1 among human tumor tissues.
Conclusions: The intensity of LAT1 expression was associated with the strength of BPA uptake. In human tumors, a trend in LAT1 expression was observed depending on the primary site and histology. The degree of LAT1 expression in tumor cells may be a useful marker for evaluating the indication for BNCT.
Keywords: Borofalan (10B); boronophenylalanine (BPA); p-BPA; LAT1; Slc7a5
Acknowledgments
None.
Funding: This work was supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid (Nos. 17H06811, 19K17231, and 21K15805).
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tro.amegroups.com/article/view/10.21037/tro-25-ab027/coif). Y.H. belongs to an endowed chair by Stella Pharma Corporation. 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. This study did not involve human or animal subjects. Data utilized from the TCGA database were publicly available and did not require further ethical approval.
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/.
doi: 10.21037/tro-25-ab027
Cite this abstract as: Watanabe T, Sanada Y, Hattori Y, Suzuki M. AB027. Exploratory study to expand the indication of boron neutron capture therapy based on LAT1 expression in tumors. Ther Radiol Oncol 2025;9:AB027.
