Biological effectiveness of boron neutron capture therapy in human glioma and melanoma cells

Abstract

Boron neutron capture therapy (BNCT) is a promising experimental method for the treatment of oncological diseases. According to results of clinical trials, patients with glioblastoma and melanoma treated with BNCT at nuclear reactors showed an increase in median overall survival and an improvement in quality of life. To obtain epithermal neutrons, new sources based on charged particle accelerators are being developed. One of the projects was implemented at the G.I. Budker Institute of Nuclear Physics, and the obtained beam parameters allowed conducting preclinical experiments. The aims were to identify the dependence of the effectiveness of BNCT in glioma and melanoma cell lines on boron concentrations using a beam generated at the accelerator based epithermal neutron source in the G.I. Budker Institute of Nuclear Physics and to evaluate prospects for using this epithermal neutron source for further clinical research. Methods. The U251 glioma cell line and the SK-Mel28 melanoma cell line were incubated with various concentrations of boronophenylalanine added to the growth medium for 24 hours and then irradiated with a neutron flux. The 10B accumulation in tumor cells was measured with an ICPE-9820 atomic emission spectrometer (Shimadzu, Japan). The effect of BNCT on glioma and melanoma cells was evaluated by the colony forming assay. Results. Analysis of the BNCT experimental data showed that the colony-forming capabilities of irradiated glioma and melanoma cells decreased in proportion to the increase in boron concentration. Thus, increasing accumulation of boron by SK-Mel 28 cells provided a greater number of dead cells with irradiation at a concentration of 10B of 25 µg/ml being a lethal dose for 100% of the cells (LD100). The glial cell line accumulated boron less intensively; death of 100% of cells occurred at a 10B concentration of 50 µg/ml. In samples irradiated without boron, the number of colonies was also decreased compared to the control due to the presence of fast neutrons and gamma-radiation components. All differences between the control and the experiment were statistically significant (p <0.05 for all). Conclusion. The results of the in vitro experiments demonstrated the effectiveness of BNCT in glioma and melanoma cell lines with the use of accelerator based epithermal neutron source in BINP and boronophenylalanine as a boron delivery agent at 10B concentrations of 6.25-50 µg/ml. Furthermore, this method proved promising for the treatment of tumors, such as glioma and melanoma.