The Measurement of the Neutron Yield of the 7Li(p,n)7Be Reaction in Lithium Targets

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 neutron flux is generated as a result of the 7Li(p,n)7Be threshold reaction using the solid lithium target. A beam shaping assembly is applied to convert this flux into a beam of epithermal neutrons with characteristics suitable for BNCT. The BNCT technique is being tested in in vitro and in vivo studies, and dosimetry methods are being developed. Currently, the BNCT technique has entered into clinical practice in the world: after successful clinical trials, two clinics in Japan began treating patients, and four more BNCT clinics are ready to start operating. The neutron source proposed at the Budker Institute of Nuclear Physics served as a prototype for a facility created for a clinic in Xiamen (China). It is planned to equip the National Medical Research Center of Oncology (Moscow, Russia) and National Oncological Hadron Therapy Center (Pavia, Italy) with the same neutron sources. Due to the impending use of an accelerator neutron source for treating patients, the validation of the neutron yield of the 7Li(p,n)7Be reaction in lithium metal targets is required. The theoretical neutron yield has not been evaluated experimentally so far.

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

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.

ASSESSMENT OF THE EFFECT OF BORON NEUTRON CAPTURE THERAPY ON TUMOR CELL LINES AND PRIMARY EMBRYONIC CELL CULTURE

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.

MODIFICATION OF MINERAL RAW MATERIAL BY RADIATION PRE-TREATMENT BEFORE PROCESSING: FEATURES AND PROSPECTS

The earlier case-studies of rebellious lead-zinc ore with grain size of -3 mm at the Chinakal Institute of Mining and Budker Institute of Nuclear Physics, Siberian Branch of the Russian Academy of Sciences provided data on improvement of disintegration selectivity and improved dissociation of useful minerals owing to preliminary treatment by a stream of electrons. The goal of this research is the integrated analysis of the change in the strength of core samples of some rocks, such as limestone, hornfels and granite, after their modification by radiation by a stream of high-energy electrons. It is found that the increase in the absorbed radiation dose results in the change in the strength and deformation properties: ultimate compression strength, modulus of deformation and elasticity modulus. In case of limestone, the ultimate uniaxial compression without radiation treatment is 49.11 MPa and drops to 35.24 MPa at the absorbed dose of 15 kGy. In case of granite, the absorption dose of 10 kGy decreases the ultimate compression strength from 68.33 to 35.08 MPa. The energy input in fracture and crushing is estimated on the equipment designed for uniaxial loading of cores at the Chinakal Institute of Mining. The energy input in fracture and crushing make 78.6 and 7004.2 J/kg for initial granite and 30.6 and 4708.8 J/kg for granite modified by radiation. The size of particle after crushing of treated cores reduces from 10.98 to 8.76 mm. The novelty of this study is the found effect of the range coverage in weakening of minerals with grain sizes to 30-50 mm, including cylindrical granite cores with diameters of 30 mm and lengths of 60 mm (equivalent spherical diameter is 43.2 mm) due to the shock waves generated in minerals during deceleration of electrons in the stream. This effect can be utilized to reduce the energy consumption of the pre-treatment technology and to minimize mineral losses in subsequent processing.

Neutron Source Based on Vacuum Insulated Tandem Accelerator and Lithium Target

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).

Preliminary experimental scaling of the helical mirror confinement effectiveness

The paper presents experimental results from the SMOLA device that is the first facility with a helical mirror section of the magnetic field. This device is built in the Budker Institute of Nuclear Physics for the verification of the helical mirror confinement idea that is the recently introduced technique of the active control of axial losses from a confinement zone. Theory predicts that with rotating plasma, a helical mirror will provide suppression of the axial plasma flow and, simultaneously, density pinching to the axis. Experiments demonstrated that plasma density at the exit from the transport section is suppressed with activation of the helical field, the effect is significant and highly reproducible. The most pronounced effect is observed on the plasma periphery, where the mirror ratio is the highest. The integral suppression ratio reaches 2–2.5 in the discussed experiments. Experimental results are compared with simplified theoretical estimates. The integral suppression ratio matches the simple theoretical estimates even if the transversal diffusion is neglected.

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

Введение. Бор-нейтронозахватная терапия (БНЗТ) является перспективной экспериментальной методикой лечения онкологических заболеваний. По данным клинических исследований пациентов с глиобластомой и меланомой, леченных БНЗТ на ядерных реакторах, отмечены рост медианы выживаемости и улучшение качества жизни. Для получения эпитепловых нейтронов ведется разработка новых источников на основе ускорителей заряженных частиц. Один из проектов был реализован в Институте ядерной физики им. Г.И. Будкера СО РАН, достигнутые параметры пучка позволяют проводить доклинические исследования. Цель работы - выявление на клеточных линиях глиомы и меланомы зависимости эффективности БНЗТ от концентрации бора при использовании пучка, генерируемого на источнике эпитепловых нейтронов ускорительного типа Института ядерной физики им. Г.И. Будкера СО РАН и оценка перспектив использования этого источника эпитепловых нейтронов для дальнейших клинических исследований. Методика. Клеточные линии U251 (глиома) и SK-Mel28 (меланома) опухолей человека инкубировали с добавлением в ростовую среду различных концентраций бора, используя препарат борфенилаланин, в течение 24 ч, затем облучали потоком нейтронов. Измерение концентрации изотопа бора 10В в опухолевых клетках проводили на атомно-эмиссионном спектрометре ICPE-9820 (Shimadzu, Япония). Клоногенный тест использовали для оценки влияния бор-нейтронозахватной терапии на клетки глиомы и меланомы. Результаты. Анализ данных БНЗТ показал, что колониеобразующие свойства облученных клеток глиомы и меланомы уменьшались с повышением концентрации бора. Так, по мере накопления бора линией SK-Mel28 увеличивается количество погибших клеток после облучения, а концентрация 10В 25 мкг/мл обеспечивает летальную дозу для 100% клеток (LD100). Глиальная линия накапливает бор менее интенсивно и гибель 100% клеток происходит при концентрации 10В 50 мкг/мл. В образцах, облученных без бора, в сравнении с контролем также наблюдалось снижение выживаемости клеток из-за присутствия быстрых нейтронов и гамма-излучения. Заключение. Данные экспериментов in vitro доказывают эффективность действия бор-нейтронозахватной терапии на клетки глиомы и меланомы при использовании источника эпитепловых нейтронов ускорительного типа ИЯФ СО РАН и борфенилаланина как агента доставки бора с концентрацией 10В 6,25-50 мкг/мл, а также перспективность использования данного метода в лечении таких опухолей, как глиома и меланома. 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.

Measurements of the tensor analyzing power T20 of the reaction γd → dπ0

The paper presents the results of measurements of the tensor analyzing power component [Formula: see text] for the coherent neutral pion photoproduction on the deuteron. The measurements were performed in the Budker Institute of Nuclear Physics using the internal tensor polarized deuterium target at VEPP-3 storage ring. The measurements covered the region of the photon energy 240 — 420[Formula: see text]MeV and the region of the center-of-mass pion polar angle 100–140[Formula: see text]. The results of measurements were compared with the calculations performed within frameworks of several theoretical models.