Neutron Source Based on Vacuum Insulated Tandem Accelerator and Lithium Target

Taskaev, S. Yu.; Berendeev, Evgeny; Bikchurina, Marina; Bykov, Timofey; Kasatov, D. A.; Kolesnikov, Iaroslav; Koshkarev, Alexey; Makarov, A. N.; Ostreinov, G. M.; Porosev, V.V.; Савинов, С. С.; Shchudlo, Ivan; Sokolova, Evgeniia; Sorokin, Igor; Sycheva, T. V.; Verkhovod, Gleb

doi:10.3390/biology10050350

Cited by 43 publications

(26 citation statements)

References 44 publications

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“…Irradiation of cell cultures was carried out at the BINP neutron source [ 3 ]. Regarding the choice of radiation dose, we relied on previously obtained data [ 24 ] showing that irradiation with these particular accelerator settings and relevant concentrations produces a therapeutic effect.…”

Section: Resultsmentioning

confidence: 99%

“…Sufficient implementation of the BNCT concept in clinical medicine requires (1) selective accumulation of 1·10 9 10 B atoms per cell or 20 μg/g of tissue, and (2) proper neutron sources with optimal characteristics. To the moment, a number of neutron sources suitable for BNCT have been fabricated, including the neutron source developed in the Budker Institute of Nuclear Physics (BINP) (Novosibirsk, Russia) [ 2 , 3 ]. BNCT showed promising results in treating different tumors, including glioblastoma multiforme, meningioma, and head and neck cancers [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with Closo-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy

Vorobyeva

Дымова

Новопашина

et al. 2021

IJMS

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Boron neutron capture therapy (BNCT) is a binary radiotherapeutic approach to the treatment of malignant tumors, especially glioblastoma, the most frequent and incurable brain tumor. For successful BNCT, a boron-containing therapeutic agent should provide selective and effective accumulation of 10B isotope inside target cells, which are then destroyed after neutron irradiation. Nucleic acid aptamers look like very prospective candidates for carrying 10B to the tumor cells. This study represents the first example of using 2′-F-RNA aptamer GL44 specific to the human glioblastoma U-87 MG cells as a boron delivery agent for BNCT. The closo-dodecaborate residue was attached to the 5′-end of the aptamer, which was also labeled by the fluorophore at the 3′-end. The resulting bifunctional conjugate showed effective and specific internalization into U-87 MG cells and low toxicity. After incubation with the conjugate, the cells were irradiated by epithermal neutrons on the Budker Institute of Nuclear Physics neutron source. Evaluation of the cell proliferation by real-time cell monitoring and the clonogenic test revealed that boron-loaded aptamer decreased specifically the viability of U-87 MG cells to the extent comparable to that of 10B-boronophenylalanine taken as a control. Therefore, we have demonstrated a proof of principle of employing aptamers for targeted delivery of boron-10 isotope in BNCT. Considering their specificity, ease of synthesis, and large toolkit of chemical approaches for high boron-loading, aptamers provide a promising basis for engineering novel BNCT agents.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with Closo-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy

Vorobyeva

Дымова

Новопашина

et al. 2021

IJMS

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“…Neutron sources have generally been used through beam shaping, in which the beam from the core of a research reactor is attenuated to increase the proportion of low-energy thermal neutrons [ 149 , 150 , 151 , 152 ]. However, in recent years, as the use of nuclear reactors has become increasingly difficult for both commercial and research purposes, high-power neutron sources, such as the Japan Proton Accelerator Research Complex (J-PARK, Tokai, Japan), have been developed in the field of physics, and research on thermal neutron sources for therapeutic use without using nuclear reactors has become popular as a spin-out of these sources [ 153 , 154 , 155 , 156 ]. Accelerator neutron sources can be installed in hospitals for medical use, and they have a higher potential for medical applications than the use of nuclear reactors because they are not subject to the strict regulations of nuclear reactors.…”

Section: Relationship Between Boron Neutron Capture Therapy (Bnct) and Boron Compoundsmentioning

confidence: 99%

A Critical Review of Radiation Therapy: From Particle Beam Therapy (Proton, Carbon, and BNCT) to Beyond

Matsumoto

Fukumitsu²,

Ishikawa

et al. 2021

JPM

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In this paper, we discuss the role of particle therapy—a novel radiation therapy (RT) that has shown rapid progress and widespread use in recent years—in multidisciplinary treatment. Three types of particle therapies are currently used for cancer treatment: proton beam therapy (PBT), carbon-ion beam therapy (CIBT), and boron neutron capture therapy (BNCT). PBT and CIBT have been reported to have excellent therapeutic results owing to the physical characteristics of their Bragg peaks. Variable drug therapies, such as chemotherapy, hormone therapy, and immunotherapy, are combined in various treatment strategies, and treatment effects have been improved. BNCT has a high dose concentration for cancer in terms of nuclear reactions with boron. BNCT is a next-generation RT that can achieve cancer cell-selective therapeutic effects, and its effectiveness strongly depends on the selective 10B accumulation in cancer cells by concomitant boron preparation. Therefore, drug delivery research, including nanoparticles, is highly desirable. In this review, we introduce both clinical and basic aspects of particle beam therapy from the perspective of multidisciplinary treatment, which is expected to expand further in the future.

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“…We focused on estimating the boron dose while classifying the impact of other significant irradiation as the sum of the three doses (GyE) (from nitrogen activation, fast neutrons, and gamma radiation) and equal to 20% of the boron dose at 40 ppm boron concentration in the sample, as previously reported [ 23 ]. As the precise calculation of dose components other than the boron-related one was beyond the purpose of this study, we used cells irradiated without boron as a control so that the survival curves reveal the isolated effect of boron ( Figure 5 ).…”

Section: Discussionmentioning

confidence: 99%

“…Neutron irradiation was carried out at the accelerator-based neutron source with a lithium neutron-producing target at the Budker Institute of Nuclear Physics (Novosibirsk, Russian Federation). This device is a prototype of a clinical BNCT facility manufactured by TAE Life Sciences, Inc. (Foothill Ranch, CA, USA) [ 10 , 13 , 22 , 23 ]. After 24-h-incubation with BPA containing 10 B (0, 10, 20, 40 µg/mL) and AuNPs (50 µg gold/mL) or BPA only, the medium was removed separately for each sample and stored.…”

Section: Methodsmentioning

confidence: 99%

Gold Nanoparticles Permit In Situ Absorbed Dose Evaluation in Boron Neutron Capture Therapy for Malignant Tumors

et al. 2021

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Boron neutron capture therapy (BNCT) is an anticancer modality realized through 10B accumulation in tumor cells, neutron irradiation of the tumor, and decay of boron atoms with the release of alpha-particles and lithium nuclei that damage tumor cell DNA. As high-LET particle release takes place inside tumor cells absorbed dose calculations are difficult, since no essential extracellular energy is emitted. We placed gold nanoparticles inside tumor cells saturated with boron to more accurately measure the absorbed dose. T98G cells accumulated ~50 nm gold nanoparticles (AuNPs, 50 µg gold/mL) and boron-phenylalanine (BPA, 10, 20, 40 µg boron-10/mL), and were irradiated with a neutron flux of 3 × 108 cm−2s−1. Gamma-rays (411 keV) emitted by AuNPs in the cells were measured by a spectrometer and the absorbed dose was calculated using the formula D = (k × N × n)/m, where D was the absorbed dose (GyE), k—depth-related irradiation coefficient, N—number of activated gold atoms, n—boron concentration (ppm), and m—the mass of gold (g). Cell survival curves were fit to the linear-quadratic (LQ) model. We found no influence from the presence of the AuNPs on BNCT efficiency. Our approach will lead to further development of combined boron and high-Z element-containing compounds, and to further adaptation of isotope scanning for BNCT dosimetry.

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Neutron Source Based on Vacuum Insulated Tandem Accelerator and Lithium Target

Cited by 43 publications

References 44 publications

Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with Closo-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy

Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with Closo-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy

A Critical Review of Radiation Therapy: From Particle Beam Therapy (Proton, Carbon, and BNCT) to Beyond

Gold Nanoparticles Permit In Situ Absorbed Dose Evaluation in Boron Neutron Capture Therapy for Malignant Tumors

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