Radiobiological response of U251MG, CHO-K1 and V79 cell lines to accelerator-based boron neutron capture therapy

Abstract

In the current article, we provide in vitro efficacy evaluation of a unique accelerator-based neutron source, constructed at the Budker Institute of Nuclear Physics (Novosibirsk, Russian Federation), for boron neutron capture therapy (BNCT), which is particularly effective in the case of invasive cancers. U251MG, CHO-K1 and V79 cells were incubated and irradiated in various concentrations of boric acid with epithermal neutrons for 2–3 h in a plexiglass phantom, using 2.0 MeV proton energy and 1.5–3.0 mA proton current, resulting in a neutron fluence of 2.16 × 1012 cm−2. The survival curves of cells loaded with boron were normalized to those irradiated without boron (to exclude the influence of the fast neutron and gamma dose components) and fit to the linear–quadratic (LQ) model. Colony formation assays showed the following cell survival rates (means ± SDs): CHO-K1: 0.348 ± 0.069 (10 ppm), 0.058 ± 0.017 (20 ppm), 0.018 ± 0.005 (40 ppm); V79: 0.476 ± 0.160 (10 ppm), 0.346 ± 0.053 (20 ppm), 0.078 ± 0.015 (40 ppm); and U251MG: 0.311 ± 0.061 (10 ppm), 0.131 ± 0.022 (20 ppm), 0.020 ± 0.010 (40 ppm). The difference between treated cells and controls was significant in all cases (P < 0.01) and confirmed that the neutron source and irradiation regimen were sufficient for control over cell colony formation. We believe our study will serve as a model for ongoing in vitro experiments on neutron capture therapy to advance in this area for further development of accelerator-based BNCT into the clinical phase.

Accelerator-based boron neutron capture therapy for malignant glioma: a pilot neutron irradiation study using boron phenylalanine, sodium borocaptate and liposomal borocaptate with a heterotopic U87 glioblastoma model in SCID mice

“…In general, the tumor growth suppression effect observed in the current study was consistent with the results of previous in vitro studies (conducted at the same accelerator at the Budker Institute of Nuclear Physics) which showed a significant suppressive effect of BNCT on the growth of U251 human glioma cells (Zaidi et al 2017), T98-G, CHO-1K, and V-79 tumor cells incubated with BPA (Sato et al 2018). In many respects, this is similar to an in vivo study of the growth of a subcutaneously implanted U87 tumor in Nu/J mice after BNCT (Kanygin et al 2019).…”

“…One of the most advanced BNCT installations exists at the Budker Institute of Nuclear Physics in Novosibirsk Science City, which is based on a tandem accelerator with vacuum insulation and a lithium target (Taskaev 2015). Due to its unique construction, a stationary proton beam with an energy of 2 MeV and a current of up to 5 mA was obtained at the facility (Ivanov et al 2016), sufficient to achieve successful in vitro and in vivo BNCT results (Zaidi et al 2017;Sato et al 2018).…”

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

“…Кроме того, что ядерный реактор нельзя установить в клинику в центре города, а также того факта, что после аварий в Чернобыле и Фукусиме в массовом сознании сформировалась радиофобия, существенным преимуществом ускорителей для лечения опухолей глубинного залегания является возможность получать терапевтический пучок нейтронов лучшего качества -преимущественно эпитепловых, с меньшим вкладом быстрых и тепловых нейтронов и γ-излучения. В настоящее время в мире разрабатывается несколько источников эпитепловых нейтронов на основе разного типа ускорителей заряженных частиц с использованием бериллиевой или литиевой мишени [11], в том числе источник нейтронов в ИЯФ СО РАН на основе ускорителятандема с вакуумной изоляцией и литиевой мишени [12,13]. На этом источнике проведен ряд исследований по изучению влияния нейтронного излучения на жизнеспособность клеточных культур U251, T98G, CHO-K1, V-79 [14].…”

Recent Advances in the Synthesis of High Boron-Loaded Nucleic Acids for BNCT

“…Sufficient application of this method in clinical medicine requires, first of all, effective and selective accumulation of boron compounds in the cancer cells. The creation of novel sources of epithermal neutrons with improved characteristics together with molecular engineering of new boron delivery agents can lead to the breakthrough in the practical use of the BNCT for the therapy of the tumors, especially those resistant to other treatments (e.g., Taskaev, 2015 ; Barth et al, 2018 ; Sato et al, 2018 ; Taskaev, 2019 ; Dymova et al, 2020 ).…”