The Expression of Markers of Acute Kidney Injury Kim1 and NGAL after Administration of High Doses of Lithium Carbonate in Mice with Engrafted Skin Melanoma B16.

The expression of marker proteins of acute kidney injury after administration of high doses of lithium carbonate was assessed to evaluate the possibility of lithium use in neutron capture therapy. In mice with implanted skin melanoma B16, the expression of Kim1 (kidney injury molecule 1) and NGAL (neutrophil gelatinase-associated lipocalin) proteins in the kidneys was evaluated immunohistochemically 15, 30, 90, 180 min, and 7 days after peroral administration of lithium carbonate at single doses of 300 and 400 mg/kg. An increase in the expression of the studied proteins was found in 30 and 90 min after administration of 400 mg/kg lithium carbonate, however, 7 days after the drug administration, the expression returned to the level observed in the control group. It can be suggested that single administration of lithium carbonate in the studied doses effective for lithium neutron capture therapy will not significantly affect the renal function.

Effects of Boron Neutron Capture Therapy on the Growth of Subcutaneous Xenografts of Human Colorectal Adenocarcinoma SW-620 in Immunodeficient Mice.

Boron neutron capture therapy (BNCT) can become an instrument for patients with malignant neoplasms of the rectum and colon. Here we evaluate the effectiveness of BNCT performed at the accelerator based epithermal neutron source at G. I. Budker Institute of Nuclear Physics, Siberian Division of Russian Academy of Sciences, in relation to subcutaneous xenografts of human colon adenocarcinoma SW-620 in SCID mice. Utilization of BNCT with boronоphenylalanine (BPA) and sodium borocaptate (BSH), which were injected intravenously into the retroorbital sinus, resulted in a significant decrease in tumor volumes compared to the control group (no radiation).

Engineering of Magnetic Softness and Domain Wall Dynamics of Fe-rich Amorphous Microwires by Stress- induced Magnetic Anisotropy.

We observed a remarkable improvement of domain wall (DW) mobility, DW velocity, giant magnetoimpedance (GMI) effect and magnetic softening at appropriate stress-annealing conditions. Beneficial effect of stress-annealing on GMI effect and DW dynamics is associated with the induced transverse magnetic anisotropy. An improvement of the circumferential permeability in the nearly surface area of metallic nucleus is evidenced from observed magnetic softening and remarkable GMI effect rising. We assumed that the outer domain shell with transverse magnetic anisotropy associated to stress-annealing induced transverse magnetic anisotropy affects the travelling DW in a similar way as application of transversal bias magnetic field allowing enhancement the DW velocity. Observed decreasing of the half-width of the EMF peak in stress-annealed microwires can be associated to the decreasing of the characteristic DW width. Consequently, stress annealing enabled us to design the magnetic anisotropy distribution beneficial for optimization of either GMI effect or DW dynamics.

Novel electrical transport properties of native Fe-Nb oxide layers leading to unilateral conductivity of a refractory metallic glass.

Fe-based metallic glasses (also called amorphous alloys) are known to have high hardness and high wear resistance. Here we study and present a Fe-Nb amorphous material with an unusual type of electrical conductivity behavior. The electrical transport properties of Fe-Nb oxide layers were studied by measuring local current-voltage characteristics by the atomic-force microscopy technique. At certain voltage levels the samples containing native oxides showed clearly asymmetrical conductivity relative to polarity of the applied potential. Fe-Nb metallic glassy surface oxide film growth process was monitored at ambient conditions. The growth rate keeps constant during the initial 2.5 hours. After that the growth rate drastically decreases and becomes almost zero while the final oxide thickness is 1.0-1.5 nm. The Fe-Nb film sample annealed for 15 minutes at 300 °C demonstrates several times larger oxide thickness and becomes an insulator. X-ray photoelectron spectroscopy was used to characterize the oxidation states in the surface amorphous oxides. This material can be readily applied as inexpensive nanoscale tunnel diode operating at the commonly utilized voltage of ±5 V.

Beam shaping assembly design of 7Li(p,n)7Be neutron source for boron neutron capture therapy of deep-seated tumor.

The development of a medical facility for boron neutron capture therapy at Budker Institute of Nuclear Physics is under way. The neutron source is based on a tandem accelerator with vacuum insulation and lithium target. The proposed accelerator is conceived to deliver a proton beam around 10 mA at 2.3 MeV proton beam. To deliver a therapeutic beam for treatment of deep-seated tumors a typical Beam Shaping Assembly (BSA) based on the source specifications has been explored. In this article, an optimized BSA based on the 7Li(p,n)7Be neutron production reaction is proposed. To evaluate the performance of the designed beam in a phantom, the parameters and the dose profiles in tissues due to the irradiation have been considered. In the simulations, we considered a proton energy of 2.3 MeV, a current of 10 mA, and boron concentrations in tumor, healthy tissues and skin of 52.5 ppm, 15 ppm and 22.5 ppm, respectively. It is found that, for a maximum punctual healthy tissue dose seated to 11 RBE-Gy, a mean dose of 56.5 RBE Gy with a minimum of 52.2 RBE Gy can be delivered to a tumor in 40 min, where the therapeutic ratio is estimated to 5.38. All of these calculations were carried out using the Monte Carlo MCNP code.

Tailoring of magnetoimpedance effect and magnetic softness of Fe-rich glass-coated microwires by stress- annealing.

There is a pressing need for improving of the high-frequency magneto-impedance effect of cost-effective soft magnetic materials for use in high-performance sensing devices. The impact of the stress-annealing on magnetic properties and high frequency impedance of Fe-rich glass-coated microwires was studied. Hysteresis loops of Fe-rich microwires have been considerably affected by stress- annealing. In stress-annealed Fe- rich microwire we obtained drastic decreasing of coercivity and change of character of hysteresis loop from rectangular to linear. By controlling stress-annealing conditions (temperature and time) we achieved drastic increasing (by order of magnitude) of giant magnetoimpedance ratio. Coercivity, remanent magnetization, diagonal and of-diagonal magnetoimpedance effect of Fe-rich microwires can be tuned by stress-annealing conditions: annealing temperature and time. Observed experimental results are discussed considering relaxation of internal stresses, compressive "back-stresses" arising after stress annealing and topological short range ordering.

[Impact of neutron radiation on the viability of tumor cells cultured in the presence of boron-10 isotope].

Objective: To investigate the impact of a neutron beam formed with the accelerator-based epithermal neutron source designed at the G.I. Budker Institute of Nuclear Physics (INP) on the viability of human and animal tumor cells cultured in the presence of boron-10 isotope. Material and Methods: Human U251 and T98G glioma cells and Chinese hamster CHO-K1 and V-79 cells were incubated at various concentrations in the culture medium containing 10B-enriched L-boronophenylalanine. The cells were irradiated with a neuron beam using the accelerator-based epithermal neuron source. A clonogenic assay was used to evaluate the viability of the irradiated cells. The absorbed doses obtained from elastic scattering of fast neutrons by substance nuclei and the doses obtained from boron neutron capture were calculated using the NMS code. The absorbed doses of gamma-radiation were measured with a mixed radiation dosimeter. Results: The viability of boron-containing and intact human U251 and T98G cell lines and Chinese hamster CHO-K1 and V-79 cells was analyzed after neutron beam radiation. Irradiation of all four cell lines were cultured in the presence of 10B was shown to reduce their colony-forming capacity compared with the control. Elevated boron levels in the culture medium resulted in a significant decrease in the proportion of survived cells. Radiation had the most pronounced impact on the proliferative capacity of the human U251 glioma cell lines. Conclusion: The cultures of human tumor cells and mammalian cells demonstrated that the neutron beam formed with the accelerator-based epithermal neutron source designed at the INP, was effective in reducing the viability of tumor cells in the presence of 10B.

Modification of the argon stripping target of the tandem accelerator.

The tandem accelerator with vacuum insulation has been proposed and developed in Budker Institute of Nuclear Physics. Negative hydrogen ions are accelerated by the positive 1MV potential of the high-voltage electrode, converted into protons in the gas stripping target inside the electrode, and then protons are accelerated again by the same potential. A stationary proton beam with 2 MeV energy, 1.6 mA current, 0.1% energy monochromaticity, and 0.5% current stability is obtained now. To conduct Boron Neutron Capture Therapy it is planned to increase the proton beam current to at least 3 mA. The paper presents the results of experimental studies clarifying the reasons for limiting the current, and gives suggestions for modifying the gas stripping target in order to increase the proton beam current along with the stability of the accelerator.

A study of gamma-ray and neutron radiation in the interaction of a 2 MeV proton beam with various materials.

Epithermal neutron source based on a tandem accelerator with vacuum insulation and lithium target has been proposed, developed and operated in Budker Institute of Nuclear Physics. The source is regarded as a prototype of a future compact device suitable for carrying out BNCT in oncology centers. In this work the measurements of gamma-ray and neutron radiation are presented for the interaction of a 2 MeV proton beam with various materials (Li, C, F, Al, V, Ti, Cu, Mo, stainless steel, and Ta). The obtained results enabled the optimization of the neutron-generating target and the high energy beam transportation path.

A new concept of a vacuum insulation tandem accelerator.

A tandem accelerator with vacuum insulation has been proposed and developed in the Budker Institute of Nuclear Physics. Negative hydrogen ions are accelerated by the positive 1 MV potential of the high voltage electrode, converted into protons in the gas stripping target inside the electrode, and then the protons are accelerated again by the same potential. The potential for high voltage and intermediate electrodes is supplied by the sectioned rectifier through a sectioned bushing insulator with a resistive divider. In this work, we propose a radical improvement of the accelerator concept. It is proposed to abandon the separate placement of the accelerator and the power supply and connect them through the bushing insulator. The source of high voltage is proposed to be located inside the accelerator insulator with high voltage and intermediate electrodes mounted on it. This will reduce the facility height from 7 m to 3m and make it really compact and attractive for placing in a clinic. This will significantly increase the stability of the accelerator because the potential for intermediate electrodes can be fed directly from the relevant sections of the rectifier.

[Possibilities of boron neutron capture therapy in the treatment of malignant brain tumors].

Boron neutron capture therapy (BNCT) that is of the highest attractiveness due to its selective action directly on malignant tumor cells is a promising approach to treating cancers. Clinical interest in BNCT focuses in neuro-oncology on therapy for gliomas, glioblastoma in particular, and BNCT may be used in brain metastatic involvement. This needs an epithermal neutron source that complies with the requirements for BNCT, as well as a 10B-containing agent that will selectively accumulate in tumor tissue. The introduction of BNCT into clinical practice to treat patients with glial tumors will be able to enhance therapeutic efficiency.

Current progress and future prospects of the VITA based neutron source.

At the BINP, a pilot accelerator based epithermal neutron source is now in use. Most recent investigations on the facility are related with studying the dark current, X-ray radiation measuring, optimization of H(-)-beam injection and new gas stripping target calibrating. The results of these studies, ways of providing stability to the accelerator are presented and discussed, as well as the ways of creating the therapeutic beam and strategies of applying the facility for clinical use.

Optimization of the target of an accelerator-driven neutron source through Monte Carlo numerical simulation of neutron and gamma transport by the PRIZMA code.

At Budker Institute of Nuclear Physics, epithermal neutron source for neutron-capture therapy was built and neutron generation was realized. Source is based on tandem accelerator and uses near-threshold neutron generation from the reaction (7)Li(p,n)(7)Be. The paper describes target optimization through the numerical simulation of proton, neutron and gamma transport by Monte Carlo method (PRIZMA code). It is shown that the near-threshold mode attractive due low activation provides high efficiency of the dose and acceptable therapeutic ratio and advantage depth.

New technical solution for using the time-of-flight technique to measure neutron spectra.

New technical solution is proposed for using the time-of-flight technique to measure neutron spectra on VITA-facility. During 200 ns the energy of protons increases from 1.865 up to 1.915 MeV by supplying the square pulse of 50 kV on the neutron-generating target, which is isolated from facility body. During these 200 ns the generation of neutrons is performed. The spectrum can be obtained measuring the time of flight by a remote neutron detector.

BINP accelerator based epithermal neutron source.

Innovative facility for neutron capture therapy has been built at BINP. This facility is based on compact vacuum insulation tandem accelerator designed to produce proton current up to 10 mA. Epithermal neutrons are proposed to be generated by 1.915-2.5 MeV protons bombarding a lithium target using (7)Li(p,n)(7)Be threshold reaction. In the article, diagnostic techniques for proton beam and neutrons developed are described, results of experiments on proton beam transport and neutron generation are shown, discussed, and plans are presented.

Effect of epithermal neutrons on viability of glioblastoma tumor cells in vitro.

We studied in vitro effect of epithermal neutrons in various doses on viability of glioblastoma U87 tumor cells. Increasing the dose from 1.9 to 4.1 Sv promoted cell death. Cytofluorimetric analysis revealed no activation of apoptosis in the irradiated cells, which attested to necrotic death of the tumor cells exposed to epithermal neutron radiation.

A neutron producing target for BINP accelerator-based neutron source.

An innovative accelerator-based neutron source for BNCT has just started operation at the Budker Institute of Nuclear Physics, Novosibirsk. One of the main elements of the facility is a lithium target producing neutrons via the threshold (7)Li(p,n)(7)Be reaction at 25 kW proton beam with energies of 1.915 MeV or 2.5 MeV. The design of an optimal target and results of the investigation of radiation blistering of the lithium layer were presented at previous NCT Congresses. During the last two years the neutron target has been manufactured, assembled and placed in the facility. Optimization of the target is carried out with the Monte Carlo simulation code MCNP. In this article, the design of the target is discussed, results of all previous investigations are summarized, results of target testing and neutron generation are described, and results of simulation of neutron spectra are presented.

First neutron generation in the BINP accelerator based neutron source.

Pilot innovative facility for neutron capture therapy was built at Budker Institute of Nuclear Physics, Novosibirsk. This facility is based on a compact vacuum insulation tandem accelerator designed to produce proton current up to 10 mA. Epithermal neutrons are proposed to be generated by 1.915 MeV protons bombarding a lithium target using (7)Li(p,n)(7)Be threshold reaction. The results of the first experiments on neutron generation are reported and discussed.

Lithium neutron producing target for BINP accelerator-based neutron source.

Pilot innovative accelerator-based neutron source for neutron capture therapy is under construction now at the Budker Institute of Nuclear Physics, Novosibirsk, Russia. One of the main elements of the facility is lithium target, that produces neutrons via threshold (7)Li(p,n)(7)Be reaction at 25 kW proton beam with energies 1.915 or 2.5 MeV. In the present report, the results of experiments on neutron producing target prototype are presented, the results of calculations of hydraulic resistance for heat carrier flow and lithium layer temperature are shown. Calculation showed that the lithium target could run up to 10 mA proton beam before melting. Choice of target variant is substantiated. Program of immediate necessary experiments is described. Target design for neutron source constructed at BINP is presented. Manufacturing the neutron producing target up to the end of 2004 and obtaining a neutron beam on BINP accelerator-based neutron source are planned during 2005.