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 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 study was to study the effect of GNP nanoparticles on tumor cells of human lung carcinoma A 549 when irradiated with protons. Materials and methods: Cell culture: Human lung carcinoma cells A 549. Gold nanoparticles Au/PEG 6000/W 200/30 nm: A colloidal solution of gold nanoparticles purchased from the firm M 9 Nanomaterials & Technologies was used in the work. Proton irradiation: The irradiation of cells was carried out on a therapeutic proton beam in the Medical and Technical Complex of the Laboratory of Nuclear Problems Joint Institute for Nuclear Research. Determination of radiosensitivity of cells: By determining the clonogenic survival of cells. Determination of the genotoxic activity of nanoparticles under the action of proton irradiation: investigated using a micronucleus test with blocking cytokinesis. The genotoxicity of gold nanoparticles was estimated by the number of micronuclei per 1000 binuclear cells. Micronucleus were counted only in binuclear cells. At least 1000 binuclear cells were calculated for each dose, experiments were carried out in three repeats. Results: The frequency of micronucleus formation indicates an increase in the genotoxic effect of nanoparticles when irradiated with protons at a dose of 2 Gy. Proton irradiation caused an increase in the frequency of micronucleus formation depending on the concentration of nanoparticles. When irradiated with protons at a dose of 2 Gy in the presence and absence of nanoparticles, the difference in the frequency of micronucleus formation for the concentration of nanoparticles was 2.5 mg/ml – 1.1; for 5 mg/ml and 10 mg/ml – 1.2; for 15 mg/ml – 1.3 and for 30 mg/ml –1.5. Cell survival curves reflect a decrease in their survival rate when metal nanoparticles with high Z are added, which reflects the occurrence of radiosensitization effects. The gain for 10 % and 50 % survival rates is 1.4 and 2.5, respectively. Conclusions: Under the influence of proton irradiation, the genotoxic activity of gold nanoparticles in human lung carcinoma cells A 549 increases, depending on their concentration. The survival rate of human lung carcinoma A 549 cells irradiated with protons in the presence of gold nanoparticles decreases.

Studies at the Medical Technical Complex (MTC) of the Joint Institute for Nuclear Research (Dubna) developed an automatic multileaf collimator (MLC) under the working name Aura for forming therapeutic proton beam of defined cross-sectional shape (aperture) for use in a passive 3D conformal radiotherapy in the treatment of oncological disease of the head and neck. A prototype collimator was constructed using four pairs of leaves and was subjected to a series of experimental tests whose results satisfied the requirements. A full-scale MLC will be used as one of the main devices in the new dynamic irradiation system for deep-seated targets of complex shape.

A new technique for dynamic irradiation of deep–seated targets of complex shape has been developed at the Medical–Technical Complex of the Joint Institute of Nuclear Research (Dubna). The technique is implemented using a variable–thickness automated range shifter and a multileaf collimator. The devices were constructed taking cognizance of the characteristics of the existing system for forming radiotherapy proton beams. Preliminary results of dosimetry measurements demonstrated better irradiation field conformity compared to the standard technique of 3D passive conformal proton radiotherapy.

Для облучения новообразований, расположенных вблизи жизненно важных радиочувствительных структур и органов необходимо обеспечить точное пространственное совмещение пучка с мишенью в сеансах протонной терапии. Целью работы является сравнение и анализ распределений доз, полученных в программе планирования протонного пучка и измеренных в результате эксперимента с применением радиохромных пленок в Медико-техническом комплексе (МТК) Лаборатории ядерных проблем (ЛЯП) Объединенного института ядерных исследований (ОИЯИ). На первом этапе измерений было определено соответствие степени потемнения пленки от дозы облучения. Для этого из одного листа пленки были вырезаны тринадцать кусочков размером 20×20 мм, которые затем облучали дозами (0; 0.25; 0.5; до 3 Гр). На их основе построена калибровочная кривая и рассчитано уравнение аппроксимации, которое использовано для перевода значений матрицы потемнения облученных пленок в значения поглощенной дозы. Продольный и поперечный спад дозы от уровня 80% до уровня 20% происходит соответственно на глубине 9.2±0.3 мм и на ширине 9.0±0.3 мм.

Для облучения новообразований, расположенных вблизи жизненно важных радиочувствительных структур и органов, разработана методика трехмерной конформной протонной лучевой терапии в Медико-техническом комплексе Лаборатории ядерных проблем Объединенного института ядерных исследований (Дубна), при которой максимум сформированного дозного распределения наиболее точно совпадает с формой мишени. При этом доза резко спадает за границами мишени, что позволяет проводить облучение ранее не доступных для лучевой терапии локализаций. В настоящей работе приводятся основные технологические этапы предлучевой подготовки и проведения облучения по разработанной методике.

This article considers an automated range shifter of variable thickness intended to adjust the proton beam energy in the 3D conformal proton radiotherapy of oncological diseases of the head and the neck. The range shifter was developed at the medico-technical complex of the Joint Institute for Nuclear Research (Dubna, Russia). The results of the experimental tests of the device show that it successfully fulfills its intended purpose. The developed range shifter is intended to be used as one of the main components of a new system for dynamic irradiation of deep-seated targets of complex shape.

A medico-technical system for hadron radiotherapy of cancer patients based on a 660-MeV proton phasotron was constructed. It is now used at the Joint Institute for Nuclear Research (Dubna, Russia). Upgrade of methods, hardware, and software for radiotherapy is one of the main tasks for further improvement of the system. This work considers the construction of a device for measurement of proton beam depth–dose curve in a treatment room, which is very important for conformal proton beam therapy and dynamic irradiation of a deeply lying target.

Effects of 7 Gy 60Co γ-radiation (acute and prolonged exposure), and combined exposure to 650 nm laser and γ-radiation on survival, peripheral blood, karyocyte count and mitotic index of bone marrow cells were studied in young C57BL/6 mice. All mice died following acute γ-irradiation at the dose rate of 1.14 Gy/min for 5 days or combined exposure for 11 days. Thirty percent survival from prolonged exposure to the dose rate of 0.027 Gy/min was observed after 19-day γ- and 38-day combined irradiation. Peripheral blood parameters did not differ significantly after acute and prolonged exposure; however, hyperchromemia was observed in mice after 24 hours of acute γ-irradiation. The count of mitoses per 1000 nucleus-containing BM cells evidenced that BM was virtually collapsed after 72 hours since the acute γ-exposure. It was demonstrated that laser can manage protection from a broad range of ionizing radiation doses and mitigate the adverse effects of equally acute and prolonged radiation exposure.

The proton beam radiosurgery was performed to 65 patients with brain AVM since December, 2001 till February, 2012, in Joint Institute for Nuclear Research, Dubna, Russia. We have analyzed data for 56 patients. The follow up time varied from 24 to 109 months. The volumes of brain AVMs varied from 0.92 to 82 cc. The mean isocenter dose was 24.61 +/- 0.12 Gy E. The edge of the target was included in 70-90% isodose. The proton beam surgery was splitted in two similar doses and delivered in two consecutive days in vast majority of patients. Ten patients were missed for follow up due to some reasons. The radiosurgery was resulted in full obliteration of AVM in 23 from remaining 46 (50%) patients. There was full obliteration in 46.6% of patients with volume of AVM 10-24.9 cc; and this rate is significantly more than for photon radiosurgery of same size brain AVM. The partial obliteration was obtained in 21 patients. Only one patients suffered hemorrhage from partially obliterated AVM. We could not see any effect in 2 patients. There were delayed radiation toxicity in 5 patients in 12 months after treatment: in 4 patients, these reactions were assessed as 2 according to RTOG scale and were dissipated in 1 month after commencement of corticosteroid treatment. There was radiation necrosis in one patient, and it was relieved in 12 months after several courses of dehydration and corticosteroid therapy. So, proton beam therapy is effective and safe modality for treatment of inoperable brain AVM, especially of middle- and large size.

A therapeutic proton beam for an actual irradiation procedure is shaped using customized collimator leaves made out of Cerrobend, while to make the proton-beam depth-dose distribution conformal to the target volume, so-called boluses (compensators) with sophisticated shapes are calculated and then fabricated to compensate for the heterogeneities of a patient’s tissues and organs in the beam path. This article describes the main stages of testing a technology for manufacturing bolus from industrial wax which was developed at the Medico-Technical Complex (MTC) at the Dzelepov Laboratory of Nuclear Problems, Joint Institute for Nuclear Research (DLNP JINR), by comparing the spatial dose distributions obtained under a computer simulation of proton irradiation and the actually measured ones under the experiment.

A series of experiments had the purpose to study effects of gamma-rays 60Co (5 Gy) and the combined effects of laser 650 nm (1 mJ/cm2) and gamma-rays 60Co (5 Gy) on survivability, body mass, integument and mitotic index of marrow cells (MC) of young mice C57BL/6. Laser was applied to the mouse hairy back only. Ten months of gamma-irradiation brought death to 50% of mice; the combined irradiation killed only 30%. Starting on month six after gamma-irradiation, body mass was less in comparison with mice exposed to the combined irradiation. In addition, all mice lost body mass sharply before death. All gamma-irradiated mice were touched with grey over the period of 30 days; in 40 days, 10 of 20 mice had incipient local radiation alopecia on the back that passed fully within next month. However, all mice developed radiation ulcers on the fourth month since irradiation. Two mice formed also neck tumors. In 5 months tails fell off in 2 mice. Some grey streaks appeared on mice exposed to the combined irradiation 3 months later only; three mice remained black throughout the follow-up. Alopecia was found in three survivors in 5 months after irradiation. Mitotic activity of marrow cells obtained from mice on day 15 since exposure to lasing and combined irradiation was higher in comparison with cells from intact mice. In a year, the MC mitotic index was higher in mice exposed to the combined irradiation as compared with the gamma-irradiated mice.

This study assessed the effect of exposure to various doses of 650 nm laser radiation, as well as of the combined irradiation to laser radiation and γ-rays^60Со (3 Gy) on the level of hemoglobin and leukocytes in peripheral blood and bone marrow karyocytes of C57BL/6 mice. The mice were irradiated with ionizing and laser radiation, separately one by one in a special frame device. Laser radiation in the dose 1 mJ/cm^2 irradiated only the back of a mouse, or both the back and the abdomen of mice. In case of combined irradiation of mice, the time interval between two types of irradiation did not exceed 30 min. First the mice were exposed to γ-radiation, then to laser radiation. The obtained results show that laser radiation stimulates blood cell formation not only in the case of irradiation with laser, but also after action of ionizing radiation. Therefore, the red spectral range laser radiation can be applied to improve the recovery of hematogenesis after the action of ionizing radiation on biological objects.