The success of
boron neutron capture therapy (BNCT) mainly depends on the
boron concentration in the
tumor and a high
tumor/normal tissue (T/N)
boron ratio or a high
tumor/blood (T/B)
boron ratio. Therefore, the effective enhancement of
boron ratios is the first priority. Our study investigated whether a low-dose of γ-radiation (LDR) could improve
boron ratios and enhance the
therapeutic effects of BNCT in an orthotopic human
oral squamous cell carcinoma-bearing animal model. SAS/luc cells were used to establish the orthotopic
tumor-bearing model. The pharmacokinetics of boronophenylalanine (BPA) administration with 400 mg/kg of
body weight both alone and in combination with LDR (0.1 Gy) was evaluated, and BNCT was performed at the Tsing Hua Open-pool Reactor (THOR). The radiation doses were evaluated using a treatment planning system. Moreover,
tumor growth and
metastasis were monitored via bioluminescence imaging (BLI). The
therapeutic effects after BNCT were evaluated using BLI, histopathological findings and the overall survival rate. LDR increased the BPA accumulation in
tumors by 52.2%. T/N and T/B ratios were enhanced from 3.77 to 5.31 and from 3.47 to 4.46, respectively. Radiation dose was increased by 44.3%. Notably,
tumor recurrence and cervical
lymph node metastasis were observed in the BNCT group, which had a survival rate of 50%. Complete responses were found in the combined-treatment group, which had a survival rate of 100%. No toxicity was found according to the histopathological findings. Conclusively, LDR increased BPA accumulation in the
tumor and the T/N and T/B ratios, resulting in BNCT efficacy improvement and the overall survival rate extension.