Radiosensitizing effect of boron enhances the effectiveness of proton therapy in vitro

Abstract

Proton therapy is used today to treat many cancers and is particularly appropriate in situations where surgery options are limited, and conventional radiotherapy presents unacceptable risks to patients. A few years ago, it was suggested that an increase of up to a factor of two of the doses at the proton Bragg peak could be achieved if boron is accumulated in the tumor tissues. The mechanism responsible for a higher dose was suggested to be related to proton-boron fusion reactions, leading to the production of high Linear Energy Transfer (LET) α-particles. Nowadays there are single works showing the effectiveness of proton beam irradiation boron-11-containing cancer cells. A limited number of the studies devoted to the application of 11B(p,3a) nuclear reaction in proton therapy and lack of consistency in their results do not allow to judge about the prospects of the boron-containing drugs utilization in proton therapy to increase its antitumor efficacy. In this work, we experimentally test the possibility to enhance proton biological effectiveness in boron-11-containing cancer cells in vitro. Human glioblastoma cells were preincubated with boron compound (Na2B4O7, sodium tetraborate) and irradiated with increasing doses 2-8 Gy at the proton Bragg peak. To test whether the physical nuclear reaction 11B(p,3a) results in an enhancement of the cancer cell death by high-energy proton beam irradiation, cell lines were also irradiated with graded doses 2-8 Gy using γ-ray source. The ability of boron compound to activate the cancer cell death with protons at the Bragg peak irradiation was shown in vitro. At the same time, weaker similar effect was determined for gamma-irradiation that may indicate not only the physical nature of influence boron at irradiated cancer cell viability but a specific biological effect. The data suggest that the combined effect of proton therapy with 11B on glioma cells increases their sensitivity to proton irradiation with low toxicity of the boron compound for cells of normal morphology.