Sensitization for proton beam therapy using ¹⁰B enriched and natural isotopic abundance of boronophenylalanine

Nuclear reactions between proton irradiation and boron via p + ¹¹B→3α (boron proton-capture reaction; BPCR) and n + ¹⁰B→α+⁷Li (boron neutron-capture reaction; BNCR) enhance the cell-killing effects of proton beam irradiation (PBI); however, which reaction exerts superior sensitization effects remains unclear. Therefore, we evaluated the efficacy of the BPCR and BNCR in enhancing the cell-killing effects of PBI. Human osteosarcoma (MG-63) and glioma (U-251 MG) cells were irradiated with PBI with and without boronophenylalanine (BPA) enriched with > 95% ¹⁰B (¹⁰B-BPA) for BNCR and BPA with natural isotopic abundance of boron (80% ¹¹B + 20% ¹⁰B; N-BPA) for BPCR. Sensitizer enhancement ratios (SERs) were obtained by comparing the doses that yielded a surviving fraction of 10% (D₁₀). The D₁₀ values for PBI alone, PBI with ¹⁰B-BPA, and PBI with N-BPA were 5.67, 4.85, and 5.51 and 5.21, 4.65, and 5.18 for MG-63 and U-251 MG cells, respectively. SERs of PBI with ¹⁰B-BPA and N-BPA were 1.17 and 1.03 and 1.12 and 1.01 for MG-63 and U-251 MG cells, respectively. Our results indicate that ¹⁰B-BPA-associated BNCR may be a better sensitizer for PBI than N-BPA-associated BPCR, which warrants further investigation into the clinical use of ¹⁰B-enriched BPA.