5-Aminolevulinic acid increases boronophenylalanine uptake into glioma stem cells and may sensitize malignant glioma to boron neutron capture therapy

Masao Fukumura, Naosuke Nonoguchi, Shinji Kawabata, Ryo Hiramatsu, Gen Futamura, Koji Takeuchi, Takuya Kanemitsu, Takushi Takata, Hiroki Tanaka, Minoru Suzuki, Oltea Sampetrean, Naokado Ikeda, Toshihiko Kuroiwa, Hideyuki Saya, Ichiro Nakano, Masahiko Wanibuchi

研究成果: ジャーナルへの寄稿学術論文査読

抄録

Boron neutron capture therapy (BNCT) is a high-LET particle radiotherapy clinically tested for treating malignant gliomas. Boronophenylalanine (BPA), a boron-containing phenylalanine derivative, is selectively transported into tumor cells by amino acid transporters, making it an ideal agent for BNCT. In this study, we investigated whether the amino acid 5-aminolevulinic acid (ALA) could sensitize glioma stem cells (GSCs) to BNCT by enhancing the uptake of BPA. Using human and mouse GSC lines, pre-incubation with ALA increased the intracellular accumulation of BPA dose-dependent. We also conducted in vivo experiments by intracerebrally implanting HGG13 cells in mice and administering ALA orally 24 h before BPA administration (ALA + BPA-BNCT). The ALA preloading group increased the tumor boron concentration and improved the tumor/blood boron concentration ratio, resulting in improved survival compared to the BPA-BNCT group. Furthermore, we found that the expression of amino acid transporters was upregulated following ALA treatment both in vitro and in vivo, particularly for ATB0,+. This suggests that ALA may sensitize GSCs to BNCT by upregulating the expression of amino acid transporters, thereby enhancing the uptake of BPA and improving the effectiveness of BNCT. These findings have important implications for strategies to improve the sensitivity of malignant gliomas to BPA-BNCT.

本文言語英語
論文番号10173
ジャーナルScientific reports
13
1
DOI
出版ステータス出版済み - 12-2023
外部発表はい

All Science Journal Classification (ASJC) codes

  • 一般

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