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The effect of a pencil scanning beam of protons at doses of 60 and 80 Gy on the solid form of Ehrlich ascites carcinoma (EAC) in mice was studied. It was shown that mice with induced EAC are a convenient model for studying hypofractionation schemes under proton therapy.

The effect of proton pencil beam scanning in the dose range of 4.5-15 Gy on the radiosensitivity of mice under irradiation in two regions of the Bragg curve was studied according to the criteria of 30-day survival, dynamics of death, and average lifespan of mice. The relative biological effectiveness (RBE) value of protons relative to X-ray radiation before and at the Bragg peak determined by the LD50/30 index was 0.86 and 0.94, respectively, and by the criterion of 30-day survival at a dose of 6.5 Gy it was 0.83 and 0.84, respectively. With similar RBE values for protons in different regions of the Bragg curve, significant differences in the dynamics of the course of radiation sickness were revealed, which indicates different damage to critical systems and organs of animals and the induction of compensatory mechanisms involved in the formation of stress responses at the organismal level.

The combined effect of the irradiation with a proton pencil scanning beam (PBS) at a total dose of 80 Gy and neutron radiation at a dose of 5 Gy on the growth of solid Ehrlich ascites carcinoma (EAC) and the remote effects in tumor-bearing mice was studied. Combined irradiation of mice with neutrons before and after irradiation with PBS, as well as irradiation only with PBS, effectively suppressed the growth of solid EAC within 1 month. In terms of the frequency and severity of radiation-induced skin reactions of mice observed 15-40 days after therapy, neutron irradiation after the irradiation with PBS showed better values of these parameters as compared to only PBS; however, exposure to neutrons before PBS was more damaging as compared to the other two options. It was also shown that the tumor relapse rate in the groups of animals with combined irradiation was higher, and the total lifespan was lower than the group of mice irradiated with PBS alone.

The effect of xylazine-zoletyl anesthesia on the radiosensitivity of mice irradiated with protons, carbon ions in two regions of the Bragg curve, and X-ray radiation was studied according to the criteria of 30-day survival, dynamics of death, and the average life span of dead mice. The maximum effect of anesthesia by 3.3 times was observed by a decrease in the death of animals during irradiation with carbon ions at the Bragg peak; in the case of irradiation before the peak, the effect was 1.2 times. In the case of proton irradiation at the Bragg peak, the protective effect of anesthesia by a factor of 1.7 was observed only at a dose of 8.5 Gy. When mice were irradiated with X-rays in the dose range of 6.0-8.5 Gy, the anesthesia effect coefficient was 1.7-2. According to the 30-day survival method, it was shown that the use of a xylazine-zoletil mixture significantly changes the radiosensitivity of mice depending on the radiation dose and the radiation source quality.

The early delayed effects of accelerated carbon ions and protons on the cognitive functions of mice using tests of the total activity, spatial learning, and long-term and short-term hippocampal-dependent memory were studied. The obtained results showed that irradiated animals do not develop an altered behavioral pattern: the level of anxiety is not increased, the exploratory model of behavior is clearly pronounced, and there is no deficiency of hippocampal-dependent memory. However, the long-term memory test revealed fewer errors in finding an escape box in a group of animals irradiated with protons compared to the control animals and mice irradiated with carbon ions. The results may indicate a better preservation of memory traces under these conditions.

The aim of this work was to study the effect of proton pencil beam scanning in the Bragg peak in the dose range of 0.1-1.5 Gy on the induction of cytogenetic damage in the bone marrow, reactive oxygen species (ROS) production in whole blood, and the state of lymphoid organs after total body irradiation of mice. Irradiation was carried out in the Prometeus proton synchrotron (Protvino) in the Bragg peak with proton energy at the output of 90-116 MeV. It was found that, under irradiation of mice in the range of low and medium doses of proton pencil beam scanning in the Bragg peak, the relative biological effectiveness (RBE) according to the criterion of cytogenetic changes was 1.15. In addition, it was found that the pathophysiological effect on the lymphoid organs and the production of ROS by blood cells were different as compared with the effect of X-rays.

The effect of proton pencil beam scanning in the dose range of 4.5-15 Gy on the radiosensitivity of mice under irradiation in two regions of the Bragg curve was studied according to the criteria of 30-day survival, dynamics of death, and average lifespan of mice. The relative biological effectiveness (RBE) value of protons relative to X-ray radiation before and at the Bragg peak determined by the LD

The combined effect of the irradiation with a proton pencil scanning beam (PBS) at a total dose of 80 Gy and neutron radiation at a dose of 5 Gy on the growth of solid Ehrlich ascites carcinoma (EAC) and the remote effects in tumor-bearing mice was studied. Combined irradiation of mice with neutrons before and after irradiation with PBS, as well as irradiation only with PBS, effectively suppressed the growth of solid EAC within 1 month. In terms of the frequency and severity of radiation-induced skin reactions of mice observed 15-40 days after therapy, neutron irradiation after the irradiation with PBS showed better values of these parameters as compared to only PBS; however, exposure to neutrons before PBS was more damaging as compared to the other two options. It was also shown that the tumor relapse rate in the groups of animals with combined irradiation was higher, and the total lifespan was lower than the group of mice irradiated with PBS alone.

In this paper we report a result of theoretical studies of the method for real-time monitoring of the Bragg peak position in a water phantom during scanned proton pencil-beam irradiation. This method is based on the detection of the prompt gamma rays emitted orthogonally to the beam direction produced as a result of inelastic nuclear interactions of primary particles. The principal parameters of the clinical setup prototype and the accuracy of determining the longitudinal coordinates of the Bragg peak position were found on the basis of statistical simulation using the RTS&T Monte Carlo multiparticle transport code.

This work focuses on the study of remote effects (duration of remission, recurrence rate, and average lifespan) in mice with Ehrlich ascites carcinoma exposed to oligofractionated irradiation with a pencil scanning beam of protons depending on the volume of the tissue being irradiated and the interval between dose fractions. The results show higher antitumor efficacy and a considerable increase in the average life span of mice after hypofractionated irradiation with a pencil scanning beam of protons at a total dose of 60 Gy of the gross tumor volume compared with the planning target volume.

On November 23, 2015 in Protvino of the Moscow Region there was begun proton therapy using Russia's first medical therapeutic complex "Prometheus" produced by JSC "PRO- TOM" and certified to treat patients with head and neck tumors. The complex allows irradiating patients with active scanning beam. Energy of beam is 30-250MeV and maximum field size is 10 cm vertically and 40 cm horizontally. The manufacturer declared parameters were confirmed during preclinical stud- ies. By April 8, 2016 the successful proton therapy received 20 patients with complex "targets" mostly located, from the point of view of radiation tolerance, near the critical structures.

The dynamics of the growth of Ehrlich ascites carcinoma in mice of the SHK line exposed to hypofractionated high-dose irradiation by a thin scanning proton beam has been analyzed for different irradiation volumes and different time intervals (from 4 to 24 hours) between two 30-Gy fractions. Irradiation of the gross tumor volume and the planned target volume was performed within the Bragg peak; the energy of protons at the outlet of the accelerator ranged from 85 to 100 MeV. Hypofractionated irradiation of the gross tumor volume of Ehrlich ascites carcinoma resulted in a more pronounced antitumor effect than the irradiation of the planned target volume. The effect did not depend on the interval between the irradiation episodes.

The purpose of this study was to investigate the combined actions of food supplements and lowdose-rate high-LET radiation on radiosensitivity, induction of the adaptive response, and tumor growth in SHK mice in vivo. The animals were irradiated with 0.11 Gy (0.005 Gy/day) of low-dose-rate high-LET radiation behind the concrete shield of a 70 GeV proton accelerator (Protvino, Moscow oblast). Four groups of the mice were fed with selected products (soy meat, buckwheat, lettuce leaves, and a drug based on cod-liver oil) during the entire irradiation period (22 days). The results of the study indicate that the mice with diets containing soy meat, buckwheat, and lettuce leaves in contrast to those fed with a diet containing cod-liver oil had reduced sensitivity to X-radiation at a dose rate of 1.5 Gy and a significant slowdown in the growth of the Ehrlich carcinoma. The combined effect of high-LET radiation and the food supplements mentioned above (except for the cod-liver oil) reduced the sensitivity of the mice to the irradiation at a dose rate of 1.5 Gy, induced the adaptive response, and caused a decrease in the growth rate of the Ehrlich carcinoma in contrast to the mice that were only irradiated with high-LET radiation.

In November 2015, the proton therapy complex “Prometheus”, developed at PhTC LPI RAS, started being used for the clinical treatment of patients with head and neck cancer. A special mobile patient positioning and immobilization device has been developed within the proton therapy complex “Prometheus”. The purpose of this paper is to report the first clinical experience of using new patient setup system in a seated treatment position. Keywords: proton therapy, ion therapy, pencil beam scanning.

ashemyakov@mail.ru In present work we investigated the cytogenetic effects induced by accelerated C ions with energy of 200 MeV/n on mice. Dose dependence, ability of the adaptive response (AR) induction and genetic instability in the generation F1 were studied by the micronucleus test in polychromatic erythrocytes (PCE) of bone marrow. Two-month-old males of SHK mice were irradiated by C ions with energy of 200 MeV/n (”Nuclotron”, Joint Institute for Nuclear Research, Dubna, Russia). A control group was exposed to X-rays. The dose dependences of the frequency of PCE with micronucleus (MN) induced with doses of 10, 15, 50 100 and 150 cGy of both types of radiation were studied. For adaptive response detection mice were exposed to irradiation according to the following scheme: an adapting doses of 10 cGy of C ions, followed after a day by a challenging dose of 1.5 Gy of X-rays (1Gy/min). To obtain generation F1, 15 days after the irradiation, males from the irradiated and control groups were mated in separate cages with unirradiated females for two weeks. This period of time was chosen because it is sufficient for the formation of spermatides, which then take part in the impregnation of the ovule. Dendants of irradiated and unirradiated parents were exposed to additional X-radiation with a dose of 1.5 Gy or by the scheme of AR to reveal the genetic instability. Bone marrow specimens for calculating micronuclei were prepared by the conventional method. The experiments demonstrated that: 1) at low doses (050 cGy) both dose-dependencies of cytogenetic damage induction can be fitted by a linear regression and almost coincide, i.e. RBE value is equal 1; at higher doses RBE value rises to 1.4; 2) irradiation of mice with dose of 10 cGy of accelerated C ions induces AR as X-radiation; and 3) the levels of spontaneous and radiationinduced PCE with MN in mice born from both males irradiated with a dose of 10 cGy of accelerated C ions and unirradiated animals is the same. The F1 generation born from irradiated males is unable to induce the AR, as distinct from their parents. The offsprings of unirradiated males reserves this ability. Obtained data indicate the genetic instability in F1 generation born from C-irradiated males. These findings may be used to assess the delayed radiation effect from low-dose of high-LET radiation and for developing basic foundation of adaptive medicine.

The paper describes a compact electron beam source ELVI-200/2 with average electron energy of 200 keV. The source operates with pulse power up to 2 MW under average power not higher than 2 kW, pulse duration 0.2÷2 mks, and repetition rate up to 5 kHz. The electron beam is extracted through aluminium – beryllium alloy foil. The pulse duration and repetition rate can be changed from control desk. High-voltage generator for the source with output voltage up to 220 kV is realized using the voltage-doubling circuit which consists of 30 sections. The insulation type – gas, SF 6 under pressure of 8 atm. The cooling of the foil supporting tubes is provided by a water – alcohol mixture from an independent source.

The serum from patients with multiple sclerosis changes electrical activity of neocortical slices of guinea pigs. This test can be used for the diagnosis of multiple sclerosis and assessment of treatment efficiency.