The Effect of Low-Dose Gamma Irradiation on the Uptake of Boronophenylalanine to Enhance the Efficacy of Boron Neutron Capture Therapy in an Orthotopic Oral Cancer Model.

Abstract

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.