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

Zavjalov, Evgenii L.; Zaboronok, Alexander; Kanygin, Vladimir; Kasatovа, Anna; Кичигин, А. И.; Mukhamadiyarov, R. А.; Разумов, И. А.; Sycheva, T. V.; Mathis, Bryan J.; Maezono, Sakura Eri B; Matsumura, Akira; Taskaev, Sergey

doi:10.1080/09553002.2020.1761039

Cited by 27 publications

(29 citation statements)

References 34 publications

(34 reference statements)

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“…As a result of studies carried out at the facility, it has been established that the neutron irradiation of U251 and T98G human glioma cells, pre-incubated in the medium with boron, leads to a significant suppression of their vitality [ 36 , 37 ]. Irradiation of immunodeficient mice with grafted human glioblastoma with pre-injection of 10 B-enriched drugs results in their reduction or suspension [ 38 ] or their complete recovery [ 7 ].…”

Section: Resultsmentioning

confidence: 99%

Neutron Source Based on Vacuum Insulated Tandem Accelerator and Lithium Target

Taskaev

Berendeev

Bikchurina

et al. 2021

Biology

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A compact accelerator-based neutron source has been proposed and created at the Budker Institute of Nuclear Physics in Novosibirsk, Russia. An original design tandem accelerator is used to provide a proton beam. The proton beam energy can be varied within a range of 0.6–2.3 MeV, keeping a high-energy stability of 0.1%. The beam current can also be varied in a wide range (from 0.3 mA to 10 mA) with high current stability (0.4%). In the device, neutron flux is generated as a result of the 7Li(p,n)7Be threshold reaction. A beam-shaping assembly is applied to convert this flux into a beam of epithermal neutrons with characteristics suitable for BNCT. A lot of scientific research has been carried out at the facility, including the study of blistering and its effect on the neutron yield. The BNCT technique is being tested in in vitro and in vivo studies, and the methods of dosimetry are being developed. It is planned to certify the neutron source next year and conduct clinical trials on it. The neutron source served as a prototype for a facility created for a clinic in Xiamen (China).

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Section: Resultsmentioning

confidence: 99%

Neutron Source Based on Vacuum Insulated Tandem Accelerator and Lithium Target

Taskaev

Berendeev

Bikchurina

et al. 2021

Biology

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“…Providing the drugs can selectively accumulate in cancer cells vs healthy cells, 41 it should be possible to manage the disease via BNCT, a non-invasive and least destructive radiation therapy currently available. [42][43][44] In order to use a drug in BNCT, it is ideal if, when not irradiated, the drug is non-toxic. In this preliminary study of synthesis, purification and toxicity of organic boron containing drug leads for BNCT applications, none of the three borylated derivatives were found to be toxic in cancer cells lines and a normal cell line (MCF10A) (Table 2).…”

Section: Cancer Assaymentioning

confidence: 99%

Borylated methyl cinnamates: Expedited synthesis, characterization, crystallographic analysis and biological activities in glycosidase inhibition and in cancer cells lines.

Legge¹,

Shimadate²,

Ghorbani³

et al. 2021

Preprint

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Three cinnamate derivatives bearing a boronate pinacol ester group para, meta and ortho to the a,b-unsaturated ester group have been synthesized via a solventless, expedited Wittig protocol in the best stereoisomeric ratios yet reported, purified by recrystallization, characterized and analyzed by X-ray crystallography. These are valuable building blocks to biologically active derivatives and are themselves biologically active drug leads, displaying excellent selectivities as glycosidase modulators and for future testing as boron neutron capture therapy (BNCT) agents. In a panel of 15 glycosidases, IC50 values of 351 mM and 374 mM were shown for para 2 against almond b-glucosidase and bovine liver b-galactosidase, respectively. For meta 2 the selectivity profile is improved with only inhibition of bovine liver b-galactosidase with an IC50 of 780 mM. These borylated derivatives also possess the capability to be used as BNCT agents. This occurs via irradiation with slow neutrons, thus granting them a switch-on/switch-off toxicity. This is an important new capability imbued into anticancer drugs, too many of which are too toxic in their therapeutic window. BNCT drugs bearing the organic boron pharmacophore have the potential to fine-tune the timing of toxicity delivery.

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“…Раствор боркаптата натрия (BSH), обогащенный изотопом 10 В>99,5 % (Katchem, Чехия), был получен путем разведения в 0,9 % растворе натрия хлорида (Renewal, Россия). Пегилированные липосомы с инкапсулированным обогащенным изотопом 10 В боркаптатом получали методом, описанным ранее [12]. Размер и заряд полученных частиц измеряли при помощи прибора ZetasizerNano ZS90 (UK).…”

Section: Laboratory and Experimental Studiesunclassified

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

et al. 2021

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Introduction. Boron neutron capture therapy (bnct) is a promising method for treating tumors, in particular, infiltrative malignant tumors, due to the selective destruction of tumor cells without damaging the surrounding normal tissues. This type of therapy is based on nuclear reaction of neutron capture by stable 10b isotope. For the successful implementation of bnct, boron delivery drugs that must be selectively accumulated in malignant cells in a sufficient amount, and a neutron source with the energy required for the neutron capture reaction are needed. At the budker institute of nuclear physics, the accelerator-based neutron source was designed with flux parameters allowing studies on bnct to be conducted.Objective: to assess the effect of bnct on tumor and normal cell lines using borphenylalanine (bpa), borcaptate (bsh) and liposomal borcaptat as boron delivery drugs.Materials and methods. Human cell cultures: glioblastoma (u87), colorectal human adenocarcinoma (sw-620), human melanoma (sk-mel28) and primary embryonic cell lines were irradiated with a neutron flux at the presence of bpa, bsh and liposomal bsh with a concentration of 10b 40 μg/ml. The short-term cytotoxic effect of irradiation was evaluated using trypan blue. Cell survival 96 hours after irradiation was determined using mtt test, and survival fraction was evaluated using the clonogenic test.Results. Early cytotoxic effects of irradiation were not observed for all 4 cell lines. According to mtt and clonogenic tests, the most pronounced effect of bnct was noticed for sw-620 and u87 lines, regardless of boron delivery drug used. For sk-mel28 line, the best effect was achieved after irradiation with liposomal borocaptate. For the primary transplanted embryonic line, high toxicity was revealed when bnct was performed with borphenylalanine and borcaptate.Conclusion. The data obtained indicate that the accelerator-based bnct using boron delivery drugs, such as borphenylalanine, borcaptate and liposomal borcaptat, has a positive effect on tumor lines of glioblastoma, colorectal adenocarcinoma and melanoma.

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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

Abstract: Taskaev (2020) 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

Cited by 27 publications

References 34 publications

Neutron Source Based on Vacuum Insulated Tandem Accelerator and Lithium Target

Neutron Source Based on Vacuum Insulated Tandem Accelerator and Lithium Target

Borylated methyl cinnamates: Expedited synthesis, characterization, crystallographic analysis and biological activities in glycosidase inhibition and in cancer cells lines.

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

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