The energy spectrum of alpha particles from the nuclear reaction p +11B- 3 alpha was studied using the beam of the injector of the proton synchrotron of the Prometheus proton therapy complex. The reaction products (alpha particles) were recorded using a CR-39 track detector. The detectors were calibrated using a241Am radioactive source. It was determined that mainly alpha particles emitted from the boron target have energies from 3 to 5.5 MeV. In this case, a significant part of the alpha particles emitted from the depths of the target have significantly lower energies compared to the calculated ones due to ionization losses. Measuring the energy spectrum of alpha particles from targets containing boron is of great scientific and practical interest for identifying the mechanisms of boron-proton capture therapy and determining the additional contribution to the therapeutic effect of proton irradiation.

The effect of high-energy (660 MeV) proton irradiation at the phasotron accelerator in FLASH mode (80 Gy/s) compared with the standard proton exposure power of 3.0 Gy/min was studied. When irradiated in two modes at doses of 1.0 and 1.5 Gy, the induction of cytogenetic damage in bone marrow cells and the state of lymphoid organs (thymus and spleen) were evaluated; survival under total in vivo irradiation of mice was analyzed at doses of 7.0 and 8.0 Gy. The growth rate of a model tumor under ex vivo irradiation was determined at doses of 40 and 60 Gy. It has been shown that irradiation of animals in the FLASH mode at a dose of 1.5 Gy protected the proliferative activity of the spleen and also led to a decrease in cytogenetic damage in bone marrow erythrocytes according to the micronucleus test compared with the standard irradiation mode at a dose of 1.5 Gy, that is, a milder effect of the FLASH mode dose was observed. However, irradiation of mice in FLASH mode at high doses (7.0 and 8.0 Gy) led to earlier death of animals compared to the standard irradiation regime. A tumor node formed with further growth only after FLASH irradiation of a suspension of Ehrlich ascites carcinoma at a dose of 40 Gy; in all other groups a tumor was not formed.

The effect of proton radiation on the induction of cytogenetic damage in the bone marrow, the production of reactive oxygen species in whole blood, and the state of the thymus and spleen depending on linear energy transfer were studied during total irradiation of mice before the Bragg peak and at the peak in the dose range 0.1–1.5 Gy. It was found that the yield of polychromatophilic erythrocytes with micronuclei at all doses of proton radiation at the Bragg peak with a linear energy transfer of 2.5 keV/μm was close to the level of linear energy transfer with micronuclei for the corresponding doses of X-ray radiation with a linear energy transfer of 2.0 keV/μm; while when irradiated before the Bragg peak with a linear energy transfer of 0.7 keV/μm, the level of cytogenetic damage was significantly lower. The coefficient of relative biological effectiveness of proton irradiation calculated from the linear energy transfer by estimating micronuclei frequency at the Bragg peak was 1.15, and before the peak it was 0.63. Organ-specific differences in the patterns of pathophysiological effects were revealed, depending on the dose and linear energy transfer of protons on the thymus and spleen of mice, as well on the state of the antioxidant system of blood cells.

The paper examines the violations of monotonicity and semiconvergence of the inverse optimization problem to equilibrium iterative solutions under conditions of physical density discontinuities in therapy planning techniques. Additionally, it addresses aspects of quasi-Newton iterations of the obtained solution in both voxel representation and continuous approximation. Examples include radiation treatment plans for patients treated with proton beam at the Prometheus therapeutic facility at the A. Tsyb Medical Radiological Research Center, Obninsk, Kaluga oblast, Russia. The presented aspects of the theory and its applications form the basis of the dose-anatomical planning program.

Introduction: Radioprotectors help to protect the body or at least minimize the negative consequences of radiation exposure. The present study aimed to assess the radioprotective potential of Helianthus tuberosus L. polysaccharide (HTLP) in vitality and micronuclei tests. To assess the cytotoxic effects of HTLP, both vitality and MTT reductase assays were conducted. Materials and methods: RAW 264.7 cells viability was assessed 24 h after adding 200 mu g/ml HTLP solution by staining cell cultures with propidium iodide and bis-benzimide to detect the nuclei of dead cells and the total number of cells in culture. To assess cell viability via cellular metabolic activity MTT test was used. In this work outbred 24-30 g 5-months old SHK mice have been used. Irradiation was provided with proton beams with an energy of 660 MeV at a dose rate of 80 Gy with doses 1.5 Gy for micronuclei test and 8.5 Gy for survival test. Whole body X-ray irradiation was conducted using the RUT-15 therapeutic X-ray unit with doses of 1.5 Gy for MN test and 6.5 Gy for survival. The HTLP sterile solution in dose 100 mu g/animal was injected into the tail vein 15 min before X-ray or proton irradiation. Results and conclusion: s: Vitality test showed no significant differences between the control group and cells treated with 200 mu l of 200 mu g/ml HTLP solution, though a greater variability was noted. In contrast, the MTT assay indicated enhanced cell viability in the HTLP-treated cells. HTLP does not exert any toxic effects in cell culture. Moreover, results of MTT reductase assay shows, that HTLP may enhance the cells' metabolic activity. Animals pre-treated with HTLP displayed a significant reduction in micronuclei formation, showing five times fewer micronuclei in bone marrow cells compared to the non-treated group. This comparison highlights HTLP's potential protective effect against radiation-induced chromosomal damage. HTLP treatment demonstrates a significant reduction in hazard compared to the control, indicating its protective effects against irradiation. Thus, it can be concluded that the use of HTLP increases the likelihood of animal survival under the ionizing effects of X-rays and protons. The survival analysis reveals that the HTLP-treated groups exhibit a higher survival rate compared to both the control and Cysteamine-treated groups, suggesting a significant protective effect of HTLP against irradiation, regardless of the type of irradiation (proton or X-ray) with p < 0.0001.

Purpose: To evaluate intrafractional motion effects as a function of peak-to-peak motion and period during single -field, single-fraction and single -field, multifraction irradiation of the moving target in spot-scanning proton therapy. Materials and Methods: An in -house dynamic phantom was used to simulate peak-to-peak motion of 5, 10, and 20 mm with periods of 2, 4, and 8 seconds. The dose distribution in the moving target was measured using radiochromic films. During the perpendicular motion, the film was fixed and moved perpendicular to the beam direction without changing the water equivalent thickness (WET). During longitudinal motion, the film was fixed and moved along the beam direction, causing a change in WET. Gamma index analysis was used with criteria of 3%/3 mm and 3%/2 mm to analyze the dose distributions. Results: For single-fraction irradiation, varying the period did not result in a significant difference in any of the metrics used ( P > .05), except for the local dose within the planning target volume ( P < .001). In contrast, varying peak-to-peak motion was significant ( P < .001) for all metrics except for the mean planning target volume dose ( P approximate to .88) and the local dose ( P approximate to .47). The perpendicular motion caused a greater decrease in gamma passing rate (3%/3 mm) than WET variations (65% +/- 5% vs 85% +/- 4%) at 20 mm peak-to-peak motion. Conclusion: The implementation of multifraction irradiation allowed to reduce hot and cold spots but did not reduce dose blurring. The motion threshold varied from 7 to 11 mm and depended on the number of fractions, the type of motion, the acceptance criteria, and the calculation method used.

A BSTRACT Proton beam therapy is being used increasingly to treat melanoma. Meanwhile, proton beam therapy has a number of disadvantages that can be reduced or completely eliminated through the use of modern innovative approaches, including the use of nanoradiosensitizers. Here we showed the possibility of using redox-active dextran-stabilized Ce 0,8 Gd 0,2 O 2 - x nanoparticles (Ce 0,8 Gd 0,2 O 2 - x NPs) as a radiosensitizer to promote mouse melanoma cell death under proton beam irradiation in vitro. It has been shown that these Ce 0,8 Gd 0,2 O 2 - x NPs do not reduce the viability and survival rate of both NCTC L929 normal mouse fibroblasts and B16/F10 mouse melanoma cells in a wide range of concentrations. However, Ce 0,8 Gd 0,2 O 2 - x NPs significantly reduce the mitochondrial membrane potential of these cells. Additionally, it has been shown that Ce 0,8 Gd 0,2 O 2 - x NPs are able to effectively reduce the clonogenic activity of B16/F10 melanoma cells under proton beam irradiation. Meanwhile, proton beam irradiation remarkably reduced the clonogenic activity and MMP of melanoma cells. Hence, Ce 0,8 Gd 0,2 O 2 - x NPs act as a radiosensitizer in B16/F10 mouse melanoma cells under proton beam irradiation. We assume that such radiosensitizing effect of Ce 0,8 Gd 0,2 O 2 - x NPs is due to a decrease of the membrane mitochondrial potential. Thus, the use of Ce 0,8 Gd 0,2 O 2 - x NPs in combination with proton beam irradiation is a promising approach for the effective treatment of melanoma.

The study of radionuclide excitation functions in proton-induced nuclear reactions is of fundamental interest for in vivo treatment verification methods in proton therapy. However, experimental data for these reactions are very limited, especially for proton energies above 20 MeV and show significant discrepancies. In the present work, experimental cross sections of reactions for accelerated protons with an energy of 160 MeV on targets of metallic calcium of natural isotopic composition are measured. For the first time, new data have been obtained on the yield cross sections of reactions with the departure of one to five protons at ^44 Ca nuclei. Calculations of the obtained cross sections in the Fermi gas and Gogny–Hartree–Fock–Bogolyubov models using the TALYS1.96 program code are carried out. It is shown that preequilibrium processes dominate in the cross sections. It is noted that the calculated cross sections, as a rule, do not exceed 30 % of the experimental ones.

The work is devoted to the dosimetric studies of a low-intensity beam for the implementation of proton radiography on the proton therapy complex Prometeus. In contrast to therapy, radiography using proton beams requires low particle fluxes, less than 1 × 106 protons/(s cm2). The controlled uniform extraction of beams of such intensity at therapeutic accelerators is a significant challenge, and it requires the development of innovative approaches. This study is part of a series of studies on the Russian medical proton synchrotron for implementing the extraction of low-intensity beams. The paper presents data on the key parameter of the extracted beam—the absorbed dose—when performing radiographic plans with a scanning beam. It also provides a quantitative analysis based on computer simulation of the spatial characteristics of proton images obtained using the extracted beam parameters.

The FLASH effect of high-energy (660 MeV) proton irradiation using the Phasotron accelerator with the capacity of delivering dose rates of 80 Gy/s has been studied and compared to the effect after exposure to proton radiation at a conventional dose rate of 3 Gy/min. After FLASH and conventional dose-rate irradiation with doses of 1.0 and 1.5 Gy, the induction of cytogenetic damage to bone marrow cells and the state of lymphoid organs (thymus and spleen) were estimated; at doses of 7.0 and 8.0 Gy, the survival rate after total irradiation of mice in vivo was analyzed; and at doses of 40 and 60 Gy, the tumor growth rate was determined after irradiation ex vivo. It has been shown that irradiation of animals using the FLASH mode at a dose of 1.5 Gy protects the proliferative activity of the spleen and also leads to a decrease in cytogenetic injuries in bone marrow erythrocytes, based on the micronucleus test, as compared to the conventional irradiation at a dose of 1.5 Gy; thus, the FLASH effect has lower toxicity compared to conventional radiation. However, irradiation of mice, the FLASH effect which delivers high doses (7.0 and 8.0 Gy) of radiation, leads to earlier death of animals compared to those exposed to conventional radiation. Only after FLASH irradiation of a suspension of Ehrlich ascites carcinoma at a dose of 40 Gy, a tumor node with further growth was formed; no tumors were formed in all other groups.

Purpose: To evaluate the effect of local proton irradiation at a dose of 30 Gy on Balb/c and C57BL/6 mice in terms of the degree and dynamics of radiation-induced skin damage formation, changes in body weight and peripheral blood elements count. Material and methods: Experiments were performed on non-depilated male mice aged 7‒8 weeks from two strains: Balb/c and C57BL/6 (n=15). Local irradiation of the skin was carried out on the dorsal side of the animals using a scanning proton beam at an extended Bragg peak in the proton therapy complex «Prometheus» of the LPI Physico-technical Centre (Protvino) at a dose of 30 Gy with a proton energy of 87.8 MeV. During the irradiation session, animals were subjected to intraperitoneal anesthesia using a combination of Zoletil 100 (Virbac, France) and Xyla (Interchemie, Netherlands) in a previously determined ratio 1:3 (20‒40 mg/kg). Photographic documentation of radiation-induced skin damage was performed weekly for 70 days. Animals were examined daily for clinical manifestations of radiation-induced skin damage formation according to the RTOG international scale for 21 days following irradiation. The body weight dynamics of mice were evaluated one day before irradiation and then weekly for 70 days. Blood samples were collected from the tail vein by cutting the tip of the tail and analyzed using a DH36 Vet hematology analyzer (Dymind, China) one day before irradiation, one day and three days after irradiation, and weekly thereafter for 70 days. Experimental data were presented as mean ± standard deviation (M ± SD). Results: In this study, the impact of a single local exposure to proton radiation at a dose of 30 Gy on the degree and dynamics of radiation-induced skin damage formation was evaluated. It was demonstrated that Balb/c mice exhibited a higher frequency and degree of radiation-induced skin damage formation compared to the C57BL/6 mice. Analysis of body weight in mice after radiation exposure revealed no significant decrease in either mouse strain. A comparative analysis of the number of platelets, erythrocytes and hemoglobin concentration in both mouse strains did not reveal any changes, while a tendency towards a decrease in the number of leukocytes, lymphocytes, and granulocytes was observed in the irradiated Balb/c mice group compared to the control group. Conversely, in irradiated C57BL/6 mice, the number of lymphocytes was higher compared to control animals. Conclusion: In this study, Balb/c mice exhibited higher radiosensitivity compared to C57BL mice in response to a single local proton irradiation at a dose of 30 Gy.

The interplay effect is a challenge when using proton scanning beams for the treatment of thoracic and abdominal cancers. The aim of this study was to evaluate the facility-specific interplay effect in terms of dose distortion and irradiation time for different beam delivery modalities, including free breathing (FB) irradiation, rescanning, deep inspiration breath-hold (DIBH), and respiratory gating. This study was carried out at a synchrotron-based facility with spot-scanning beam delivery. A motion phantom with a radiochromic film was used to measure dose distributions. Regular and irregular motion patterns were studied. Dose homogeneity and the gamma index were calculated to quantify the interplay effect. The interplay effect significantly decreased the homogeneity and gamma passing rate by 12% and 46%, respectively, when FB irradiation without motion mitigation was used for 20 mm peak-to-peak motion. Rescanning and DIBH partially mitigated the distortions but doubled the irradiation time, while gating provided the superior dose distribution with only a 25% increase in time compared to FB irradiation without mitigation. The interplay effect was a function of motion amplitude and varied with the beam delivery modality. Gating may be a more preferable technique for the synchrotron-based facility in terms of minimizing dose distortion and treatment time.

Purpose: To investigate a novel optical markerless respiratory sensor for surface guided spot scanning proton therapy and to measure its main technical characteristics.Methods: The main characteristics of the respiratory sensor including sensitivity, linearity, noise, signal-to-noise, and time delay were measured using a dynamic phantom and electrical measuring equipment on a laboratory stand. The respiratory signals of free breathing and deep-inspiration breath-hold patterns were acquired for various distances with a volunteer. A comparative analysis of this sensor with existing commercially available and experimental respiratory monitoring systems was carried out based on several criteria including principle of operation, patient contact, application to proton therapy, distance range, accuracy (noise, signal-to-noise ratio), and time delay (sampling rate).Results: The sensor provides optical respiratory monitoring of the chest surface over a distance range of 0.4-1.2 m with the RMS noise of 0.03-0.60 mm, SNR of 40-15 dB (for motion with peak-to-peak of 10 mm), and time delay of 1.2 & PLUSMN; 0.2 ms.Conclusions: The investigated optical respiratory sensor was found to be appropriate to use in surface guided spot scanning proton therapy. This sensor combined with a fast respiratory signal processing algorithm may provide accurate beam control and a fast response in patients' irregular breathing movements. A careful study of correlation between the respiratory signal and 4DCT data of tumor position will be required before clinical implementation.

An Erratum to this paper has been published: https://doi.org/10.3103/S1068335623020112

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.

— Main elements of the X-ray system of the Prometheus proton therapy complex are described. The system is integrated into the proton synchrotron outlet socket (exit cone), and allows X-ray micrographs and cone beam tomography of the patient body area of interest. The system is successfully used in clinical practice to verify the patient position immediately before irradiation.

The yield of the nuclear reaction B + p → 3α near the resonant proton energy of 675 keV in the injector beam of the “Prometheus” proton accelerator is studied. The reaction products (alpha particles) are recorded using a CR-39 track detector. The alpha particle yield from the boron target is estimated as ~10 –4 per proton.

The Prometheus proton therapy complex is a scalable serial medical facility dedicated to proton therapy. In addition to its clinical applications, the facility also enables research in such fields as radiobiology, medical physics, and materials science. This work provides a brief overview of the key fields of research and results achieved using this facility. The experience with this complex demonstrates its effectiveness in establishing centers for collective use, capable of addressing a broad range of clinical, fundamental, and interdisciplinary scientific challenges.

Radiation dermatitis (RD) is one of the most common side effects of radiation therapy. However, to date, there is a lack of both specific treatments for RD and validated experimental animal models with the use of various sources of ionizing radiation (IR) applied in clinical practice. The aim of this study was to develop and validate a model of acute RD induced using proton radiation in mice. Acute RD (Grade 2–4) was obtained with doses of 30, 40, and 50 Gy, either with or without depilation. The developed model of RD was characterized by typical histological changes in the skin after irradiation. Moreover, the depilation contributed to a skin histology alteration of the irradiated mice. The assessment of animal vital signs indicated that there was no effect of proton irradiation on the well-being or general condition of the animals. This model can be used to develop effective therapeutic agents and study the pathogenesis of radiation-induced skin toxicity, including that caused by proton irradiation.