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.