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. 2023 Jan 24;13(1):1341.
doi: 10.1038/s41598-023-28428-z.

Experimental validation of proton boron capture therapy for glioma cells

Affiliations

Experimental validation of proton boron capture therapy for glioma cells

Tatiana Shtam et al. Sci Rep. .

Abstract

Proton boron capture therapy (PBCT) has emerged from particle acceleration research for enhancing the biological effectiveness of proton therapy. The mechanism responsible for the dose increase was supposed to be related to proton-boron fusion reactions (11B + p → 3α + 8.7 MeV). There has been some experimental evidence that the biological efficiency of protons is significantly higher for boron-11-containing prostate or breast cancer cells. The aim of this study was to evaluate the sensitizing potential of sodium borocaptate (BSH) under proton irradiation at the Bragg peak of cultured glioma cells. To address this problem, cells of two glioma lines were preincubated with 80 or 160 ppm boron-11, irradiated both at the middle of 200 MeV beam Spread-Out Bragg Peak (SOBP) and at the distal end of the 89.7 MeV beam SOBP and assessed for the viability, as well as their ability to form colonies. Our results clearly show that BSH provides for only a slight, if any, enhancement of the effect of proton radiation on the glioma cells in vitro. In addition, we repeated the experiments using the Du145 prostate cancer cell line, for which an increase in the biological efficiency of proton irradiation in the presence of sodium borocaptate was demonstrated previously. The data presented add new argument against the efficiency of proton boron capture therapy when based solely on direct dose-enhancement effect by the proton capture nuclear reaction, underlining the need to investigate the indirect effects of the secondary alpha irradiation depending on the state and treatment conditions of the irradiated tissue.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Cytotoxicity of sodium borocaptate (BSH) for A172 (A), Gl-Tr (B) glioma cells, Du145 prostate cancer cells (C), and DF-2 fibroblasts of human skin (D). The cytotoxic effects of BSH at 0—1000 ppm of 11B concentration have been studied by the AlamarBlue cell viability assay after 7 h or 18 h of incubation.
Figure 2
Figure 2
Distribution of A172 (A), Gl-Tr (B) glioma cells, and Du145 prostate cancer cells (C) over the phases of the cell cycle after incubation with sodium borocaptate (BSH) at a boron-11 concentration of 80 ppm for 7 h (up panels) or 18 h (bottom panels).
Figure 3
Figure 3
Effect of BSH on cell viability after exposure to Bragg peak protons at different absorbed dose. Summary plots for AlamarBlue cell viability assays: (A) A172 cells, (B) Gl-Tr cells, (C) DU145 cells (dashed lines). The cells were incubated in a medium containing 80 ppm of boron-11 for 7 h (up panels) or 18 h (bottom panels) and then irradiated by 89.7 MeV clinical proton beam in a dose range of 0–6 Gy. Data were fitted with a linear-quadratic function of the radiation dose (solid lines). Each plot summarizes the results of three independent irradiation experiments.
Figure 4
Figure 4
Effect of BSH on cell colony formation after exposure to Bragg peak of 89.7 MeV clinical proton beam. Summary plots for colony assays: (A) A172 cells, (B) Gl-Tr cells, (C) Du145 cells (dashed lines). Data were fitted with a linear-quadratic function of the radiation dose (solid lines) with the parameter β constrained to non-negative values. The cells were incubated in a medium containing 80 ppm of boron for 7 h (up panels) or 18 h (bottom panels) and then irradiated by 89.7 MeV clinical proton beam in a dose range of 0–6 Gy. After treatment, 103 cells were seeded out to form sufficiently large clones consisting of 50 or more cells. Colony formation assay was performed in 10–14 days. Each plot summarizes the results of three independent experiments.
Figure 5
Figure 5
Comparison of cell survival under combined exposure to 80 ppm boron-11 and irradiation at the middle position of Spread-Out Bragg Peak of 200 MeV proton beam. Summary plots for AlamarBlue (up panels) and colony forming assays (bottom panels): (A) A172 cells, (B) Gl-Tr cells, (C) Du145 cells. The cells were incubated in a medium containing 80 ppm of boron-11 for 18 h and then irradiated by 200 MeV proton beam in a dose range of 0–6 Gy. Data were fitted with a linear-quadratic function of the radiation dose (solid lines) with the parameter β constrained to non-negative values.
Figure 6
Figure 6
Cell viability after incubation of cells with 160 ppm of boron-11 and exposure to Bragg peak of 89.7 MeV clinical proton beam. Summary plots for AlamarBlue (up panels) and colony forming assays (bottom panel): (A) A172 cells, (B) Gl-Tr cells, (C) Du145 cells. The cells were incubated in a medium containing 160 ppm of boron-11 for 18 h and then irradiated at the distal position of 89.7 MeV clinical SOBP in a dose range of 0–6 Gy. Experimental data (dashed lines) were fitted with a linear-quadratic function of the radiation dose (solid lines) with the parameter β constrained to non-negative values.
Figure 7
Figure 7
Effect of BSH on cell survivability after exposure to Bragg peak protons at different absorbed dose. (A) Dose profile for irradiation of cells with an 89.7 MeV clinical proton beam. In the majority of experiments, the cells were positioned at a depth of 30 mm (I position), and in some—at a depth of 32 mm (II position) along clinical proton SOBP. (B) Examples of colony forming assays for 7 h of incubation of Du145 cells with BSH (0 ppm (Control) or 250 ppm of boron-11) and proton beam irradiation at I position or II position of proton SOBP. (C,D) Plots for AlamarBlue (up panels) and colony forming assays (bottom panels) of Du145 cells. The cells were incubated in a medium containing 250 ppm of boron-11 and then irradiated by proton beam in a dose range of 0–6 Gy at (C) I position or (D) II position of SOBP of 89.7 MeV clinical proton beam.

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