The effect of carbon ions (12C) with the energy of 400 MeV/nucleon on the dynamics of induction and growth rate of solid tumors in mice under irradiation of Ehrlich ascites carcinoma cells (EAC) ex vivo at doses of 5-30 Gy relative to the action of equally effective doses of X-ray radiation was studied. The dynamics of tumor induction under the action of 12C and X-rays had a similar character and depended on the dose during 3 months of observation. The value of the latent period, both when irradiating cells with 12C and X-ray, increased with increasing dose, and the interval for tumor induction decreased. The rate of tumor growth after ex vivo irradiation of EAC cells was independent of either dose or type of radiation. The dose at which EAC tumors are not induced within 90 days was 30 Gy for carbon ions and 60 Gy for X-rays. The value of the relative biological effectiveness of carbon ions, calculated from an equally effective dose of 50% probability of tumors, was 2.59.

Radiosensitivity to low and medium doses of X-ray radiation and the ability to induce a radiation adaptive response (RAR) of lymphocytes during in vitro irradiation of peripheral blood of patients with cancer were studied. The criterion for cytogenetic damage was the frequency of micronuclei (MN) in cytochalasin-blocked binucleate lymphocytes in culture. It was found that the spontaneous level of cytogenetic damage in the lymphocytes of patients was 2.6 times higher than in healthy volunteers, and there was also significant interindividual variability in values compared to the control cohort. There were no differences in mean values for radiosensitivity to low and medium doses of X-ray between the study groups. There was no correlation between the spontaneous level of MN in lymphocytes and the radiosensitivity of individuals in both groups. RAR was induced with the same frequency and to the same extent in lymphocytes from both patients and healthy individuals.

The data of the study of the radioprotective properties of nanocerium (nCeO2) after total irradiation of mice with carbon ions in medium and lethal doses according to the micronucleus test and the criterion of 30-day survival are presented. A significant protective effect of nCeO2 upon irradiation at medium doses was observed at per os administration for 5 days before irradiation (that is, at long-term prophylactic use). Mouse survival data showed no protective effect of per os administration of nCeO2 in contrast to the micronucleus test results. After injections of both nCeO2 and saline solution 24 h before or immediately after irradiation, the radioprotective effect was detected using both methods. The data obtained revealed the dependence of the observed effects on the mode and time of nCeO2 administration, the influence of the solvent, the level of doses and the quality of radiation, as well as demonstrated the possibility of using nanocerium preparations to protect organisms from radiation with high LET values and the importance of further studies of the radioprotective properties of new nanomaterials.

This study presents data on the growth rate and frequency of induction of the solid form of Ehrlich's ascites carcinoma (EAC) in mice in the short and long term after inoculation of ascitic cells irradiated ex vivo with a proton beam in the dose range of 30-150 Gy. It was shown that the growth rate of solid tumors after inoculation of irradiated cells ex vivo coincided with the growth of tumors in the control group. The frequency of tumor induction in mice after inoculation of EAC cells irradiated at a dose of 30 Gy was 80%, 60 Gy-60%, 90 Gy-25%, and 120 Gy-10%; at irradiation at a dose of 150 Gy, no tumors appeared during the entire observation period. Thus, we determined the dose of proton radiation required to eliminate tumor cells and/or signaling factors that can lead to the induction of tumor growth of EAC in mice.

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 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 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.

Physical-Technical Center of P.N. Lebedev Physical Institute of RAS and Protom Ltd. are engaged in development and implantation of synchrotrons for proton therapy into clinical practice. There are two proton therapy complexes “Prometheus” in Russia. That are fully developed and manufactured at Physical-Technical Center and Pro-tom. Every day patients with head and neck cancer get treatment using "Prometheus" at the A. Tsyb Medical Ra-diological Research Center. At the moment these facilities together have accumulated more than 5 years of clinical experience. Two facilities are based on the Protom syn-chrotrons in the USA. One operates at the McLaren Hospital PT Center, it started to treat patients in 2018. Another one is as a part of the single-room proton therapy system “Radiance330” in Massachusetts General Hospital that went into clinical operations in 2020. The first Israel proton therapy complex based on Protom synchrotron was launched in 2019. Protom facilities provide full stack of modern proton therapy technologies such as IMPT and pencil beam scanning. Key features of Protom synchrotron: low weight, compact size and low power consumption allow it to be placed in conventional hospitals without construction of any special infrastructure. This report presents current data on accelerator re-searches and developments of Physical-Technical Center and Protom Ltd. In addition, it provides data on the use of Protom based proton therapy complexes under the clinical conditions.

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 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 purpose of the work was to study the growth of solid Ehrlich ascites carcinoma (EAC) and the remote effects (duration of remission, relapse rate, and average lifespan) in tumor-bearing mice exposed to oligofractionated irradiation with the pencil beam scanning of protons (PBSP) at a total dose of 60 Gy depending on the volume of the tissue being irradiated.Experiments were carried out on eight-to nine-week-old SHK male mice.Mice were irradiated with two fractions, 30 Gy each.In order to determine the volume of irradiated tissue, a tomogram of a mouse in a water phantom was obtained, and a gross tumor volume (GTV) that is equal to the average size of 470 mm 3 from all mice was specified using a specially developed 3D planning system.In another group of animals, the irradiated tissue region was increased to the planning target volume (PTV), which was equal to 1500 mm 3 .An analysis of EAC growth dynamics during the first month showed higher irradiation efficiency in mice with a smaller irradiated volume (the GTV group) compared with the PTV group.In the group with GTV irradiation, survival was higher: the maximum life expectancy in mice without relapse was 5 months longer, and in mice with relapse it was 3 months longer than in the PTV group.The average lifespan (AL) of mice with EAC relapses in the group with GTV irradiation was higher compared to the group with PTV irradiation (96 and 77 days after irradiation or 58 and 31 days after the occurrence of a relapse, respectively; p ≤ 0.01).The AL of mice without tumors was also notably longer in the GTV group: 283 days compared to 228 days after PTV irradiation (p ≤ 0.01).

Abstract 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.

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.

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.