Cytopathic Effects of Accelerator-Based Boron Neutron Capture Therapy on Human Glioblastoma Cells

Abstract

Boron neutron capture therapy (BNCT) is a targeted therapy based on a selective damage to cancer cells due to the interaction between boron-10 isotope and neutron. Reactor-based BNCT has been found to be effective in the treatment of high-grade gliomas. It is believed that compact accelerator-based neutron sources will ensure widespread adoption of the technique in clinical practice. New accelerator-based neutron sources are being actively developed all over the world. At the Institute of Nuclear Physics (Russia), the accelerator-based neutron source was developed for pre-clinical studies of BNCT.Purpose: to determine the cytopathic effects of accelerator-based BNCT on the human U87-glioblastoma cell line and to select a concentration of boron drugs that do not have a toxic effect on the cells before irradiation in vitro.Material and Methods. To assess the cytopathic effects (MTT test and colony-forming assay) of various concentrations of boron-containing drugs, U87 cells were incubated with boronophenylalanine (BPA) and sodium borocaptate (BSH) for 1, 2 and 10 days. The effect of BNCT on the U87 cell line was determined using colony-forming assay.Results. The MTT test showed a decrease in cell survival at a boron-10 isotope concentration of 160 μg/ml after 48 hours and 640 μg/ml after 24 hours of incubation for BPA. The cytopathic effects for sodium BSH appeared at a boron concentration of 80 µg / ml after 48 hours of incubation, and survival fraction of cells was reduced to 89 % compared to the control. According to the colonyforming assay, the cytotoxic effects of BSH and BPA at a boron concentration of 40 µg/ml in the medium were 79.6 and 84 %, respectively. The proportions of surviving cells were 18 ± 2 % and 13 ± 2 % after epithermal neutron irradiation in the presence of boronophenylalanine and in the presence of sodium borocaptate, respectively. Cell death without boron drugs occurred due to the neutron elastic scattering, nuclear reactions of thermal neutron capture by hydrogen and nitrogen, and accompanying gamma radiation.Conclusion. The study clearly showed a decrease in the proportion of surviving U87 cells after accelerator-based BNCT in the presence of 10B-enriched BSH and BPA.

Assessment of the Effect of Boron Neutron Capture Therapy on Tumor Cell Lines and Primary Embryonic Cell Culture

“…Ещё одно исследование проведено на клеточной линии U87, которую предварительно инкубировали с препаратами бора и затем облучали эпитепловыми нейтронами. Проведенная бор-нейтронозахватная терапия приводила к снижению выживаемости клеток более чем в 2 раза в сравнении с контролем и составила 18 % при инкубировании с BPA и 13 % -с боркаптатом (BSH) [8].…”

Radiobiological Effectiveness of the Accelerator-Based Neutron Beam in Vitro and in Vivo at the Binp at the Budker Institute of Nuclear Physics

“…1А, Б). Наши данные согласуются с предыдущими исследованиями по облучению клеточных линий U251MG, CHO-K1, V79 на ускорителе с током 1,5-3,0 мA при энергии протонов 2 МэВ [9], а также по аналогичному облучению клеточной линии U87 пучком с энергией протонов 2 МэВ и током 2,6 мА [11]. А.…”

Gadolinium Neutron Capture Therapy for Cats and Dogs with Spontaneous Tumors Using Gd-DTPA

“…In many countries, preclinical radiobiological studies are required prior to treating human malignancies with accelerator-based NCT. In this case, studies using cells and animal tumor models play a key role [45,47]. However, cell and tumor models in laboratory animals cannot fully repeat the complex morphology of spontaneous tumors.…”