Introduction. Biological dose uniformity in SOBP of the modem proton therapy facilities is an important issue. The results of a number of studies reveal an increased biological efficiency at the distal area of SOBP.The aim of the study was to verify this effect for Prometeus facility, which provides proton therapy with a scanning pencil beam.Material and methods. The study was conducted at A. Tsyb MRRC. Melanoma B16F10 cells were used for the experiments. The biological efficacy of protons was evaluated by clonogenic assay (cell survival) and comet assay (DNA damage). Proton dose range within the experiments was 4-8 Gy. Cells were irradiated both in monolayer and suspension conditions. Proton biological efficacy along SOBP was evaluated in the proximal, middle and distal positions. All irradiations were carried out with one field.Results of in vitro experiments indicate that Prometeus facility treatment planning system in case of single-field irradiation provides the uniformity of the biological dose in SOBP. According to cell survival, there is a tendency for a slightly greater efficiency of protons in the proximal part of SOBP. Data on DNA damage confirm this conclusion.Conclusion. Therefore, unlike a number of modern installations for proton therapy in the case of the facility used in the study, there is no increase of biological dose in the distal area of SOBP.
The basis for the use of protons for radiation therapy tasks is a fixed conventional value of their relative biological efficiency equal to 1,1. Numerous studies have showed that RBE of proton radiation is not a constant value and depends on a number of factors. The purpose of this study was to determine RBE of a thin scanning proton beam at the center of the distributed Bragg peak in experiments on the culture of murine B-16 melanoma cells. The cell suspension was irradiated in an aqueous phantom by a horizontal proton beam from three directions (0,90 and 180°) in doses from 2 to 8 Gy. Modulation of the energy of proton radiation was 47,5÷92,0 MeV. RBE protons were determined from the clonogenic activity of the cells compared with 60Co gamma quanta. A linear-quadratic model was used to construct the dose dependencies. Obtained RBE values of proton radiation (LET 3÷8 keV/μm) differed in the big party from the generally accepted value and was at the level of 10% survival rate of 1.5. The results obtained generally coincided with data of foreign authors performed on different facilities.
The paper presents some outcomes obtained during the year of 2013 of the activity in the frame of the International Atomic Energy Agency Co-ordinated research project "Investigations of Materials under High Repetition and Intense Fusion-Relevant Pulses". The main results are related to the effects created at the interaction of powerful pulses of different types of radiation (soft and hard X-rays, hot plasma and fast ion streams, neutrons, etc. generated in Dense Plasma Focus (DPF) facilities) with various materials including those that are counted as perspective ones for their use in future thermonuclear reactors. Besides we discuss phenomena observed at the irradiation of biological test objects. We examine possible applications of nanosecond powerful pulses of neutrons to the aims of nuclear medicine and for disclosure of hidden illegal objects. Special attention is devoted to discussions of a possibility to create extremely large and enormously diminutive DPF devices and probabilities of their use in energetics, medicine and modern electronics.
We describe a technique for attaining extended transversally-flat paraxial dose fields with the intermediateenergy carbon beam slowly extracted at the magnetic-field flat-bottom from the IHEP U-70 synchrotron. To this end, a fixed-radius circular beam sweep with the aid of a compact electromechanical wobbler with rotating permanent dipole magnets is applied. A technique for tuning the beam transfer line and the irradiation facility proper at the interim radiobiological workbench with an external fixed target is substantiated. A brief description of its engineering implementation is presented. Results of the successful experimental verification of the technique in question with a carbon nuclear beam from the U-70 machine are reported, in particular, results of the primary radiobiological exercises accomplished in cooperation with the scientists at the MRRC of the Russian Ministry of Healthcare.
Potassium 7,8-dicarba-nido-undecaborate was thiocyanated by nondiaphragm electrolysis. The salt Me4N+[9-SCN-7,8-C2B9H11]− was isolated and converted into the trimethylammonium salt using ion-exchange. Methods for the synthesis of water-soluble sodium 7,8-dicarba-nido-undecaborate and its biphasic iodination (for 131I introduction) were developed. Thus, the synthesis and analysis of the radioactive iodine-labeled sodium salt of 11-(131I)-9-thiocyanato-7,8-dicarba-nido-undecaborate were proposed and carried out. The toxicity of the synthesized compound was evaluated. It was established that 100 and 75 mg/kg doses are 100% lethal for test animals while no significant disorders were observed at doses of 35 and 20 mg/kg. The biodistribution of the compound in organs and tissues was studied in mice with melanoma B-16. The maximum accumulation of labeled compound in tumor, skin, muscle, liver, kidneys, and spleen was observed 3 – 6 h after administration. A comparison of drug accumulation in tumor and normal tissues showed that the preparation does not possess pronounced tumor-targeting properties.
The biodistribution of sodium mercaptododecaborate labeled with radioactive iodine (131I-BSH) in melanoma B-16 and surrounding tissues in mice has been studied for administration by various methods including intraperitoneal, single and double intratumor injection, and introduction under tumor bed. It is shown that a high content of 131I-BSH in the tumor is reached in all cases. The maximum accumulation of the boron compound is observed 1 h after administration. In this case the ratio of radioactivities in melanoma B-16 and surrounding tissues in most animals was greater than 3. A study of 131I-BSH uptake in tumor cells showed that a considerably greater accumulation of the compound is observed 3 and 6 h after intraperitoneal administration in the intercellular space (65.3% and 63.0%, respectively) in comparison to the cellular content (34.7% and 37.0%, respectively). The levels of accumulation become identical in about 12 h after administration. Approximately equal uptake of the boron compound in the intercellular space and tumor cells was observed over the entire period of investigation (0.5–2 h) after a single intratumor administration of 131I-BSH. The results of this study suggest that the intratumor administration of boron compounds is promising for neutron capture therapy, especially in combination with neutron teletherapy.
The influence of vasodilative (dibazole) and vasoconstrictive (mesatone) drugs on the distribution of sodium mercaptododecaborate labeled with radioactive iodine (131I-BSH) in melanoma B-16 and surrounding tissues of mice has been studied. It is shown that the administration of dibazole results in a more pronounced increase in the ratio of 131I-BSH concentrations in the tumor and surrounding tissues in comparison to mesatone. Combined use of infrared radiation and dibazole for the modification of 131I-BSH distribution in tissues showed a tendency to increase in the ratio of BSH concentrations in the tumor and tissues in comparison to the case of infrared irradiation or dibazole used alone. The results show good prospects for the combined use of IR radiation and drugs for increasing the oncotropic properties of agents for boron neutron capture therapy.
The influence of local IR irradiation of the experimental melanoma B-16 zone on the distribution of sodium mercaptododecaborate labeled with radioactive iodine (131I-BSH) in mice was studied for two regimes of thermal treatment (before and after administration of the labeled compound). It was established that a considerable increase in the 131I-BSH content in the model tumor was reached in the case of IR irradiation performed 1 h after drug administration. Based on these data, IR radiation can be considered an effective modifier of 131I-BSH uptake in tumors, increasing the efficacy of boron-enhanced neutron capture therapy.
The distribution of sodium mercaptododecaborate labeled with radioactive iodine (131I-BSH) in the organism of mice with melanoma B-16 was studied with the aid of a gamma camera. The 131I-BSH distribution in the whole organism coincides with that of its unlabeled analog. This result facilitates the solution of problems related to the planning and monitoring of boron neutron capture therapy.
A scintillation detector is used to investigate the leakage spectrum of internal conversion electrons produced from gadolinium by the capture of thermal neutrons in a thin layer of gadolinium. Thermoluminescence dosimeters are used to measure the dose of prompt γ-rays from gadolinium. The measurements are performed in the thermal column of a BFS-2 critical assembly and in a thermal-neutron beam extracted from a BR-10 reactor.
Investigation of Kumakhov halflenses for thermal neutron focusing was carried out on the monochromatic beam of horizontal channel at the Karpov Institute WWR-ts reactor. Efficiency and gain coefficient were measured for two halflenses. Estimation of real halflens focal spot for focused neutron monochromatic beam was made.
Since the beginning of implementation of the method of boron neutron capture therapy (BNCT), several hundred boron-containing compounds have been synthesized for this purpose. The main requirement of these substances is the ability to be taken up by tumor cells with insignificant accumulation in the surrounding tissues. After many years of investigations aimed at the clinical realization of BNCT, two substances were selected among all candidates – sodium mercaptododecaborate Na 2 B 12 H 11 SH (BSH) and p-borophenylalanine ( p-BPA) – and used until now. Although the clinical experience gained from these investigations showed that neither of the two agents is ideal from the standpoint of BNCT, BSH was nevertheless successfully applied in the combined treatment of brain tumors, and p-BPA in the treatment of skin melanoma and related metastases [1]. Parallel investigations conducted presently are devoted to the possibility of using BSH and p-BPA in the treatment of other tumors and to the search for new, more effective boron-containing compounds for BNCT. For implementing BNCT into practical oncology in Russia, it is necessary to solve a complex of physical, engineering, chemical, biological, and medical problems. The chemical part includes elaboration of the synthesis of boron-containing compounds already used in world BNCT practice and the R&D of new domestic agents comparable with the foreign analogs in their ability to be taken up by tumors. Several years ago, a domestic technology was developed for the synthesis of a new agent, rhodandodecaborate [B 12 H 11 SCN] 2– (BSCN) [2], capable of accumulating in experimental tumors (melanoma B-16 and glioblastoma in greater amounts as compared to BSH [3]). After developing a method for labeling the two compounds with radioactive iodine, we have studied the pharmacokinetics of 131 I-BSH and 131 I-BSCN [4, 5]. The purpose of this study was to compare the dynamics of distribution of these labeled compounds in the organs and tissues of experimental animals.
A method for performing direct measurements of the energy of the neutron-capture reaction on gadolinium is proposed and tested. Measurement of the absorbed dose is an important problem for gadolinium neutron-capture therapy.
A new variant of a solid-state detector adapted for estimating the10B content in biological tissue was developed. A new polymeric composition based on oligoester acrylates was used as the detector. The number of tracks is a linear function of the boron content in the concentration range 0.5–200 μg10B/g inbiological sample samples with mass 100–500 μg. The detector can be recommended for deterning10B in biological tissues, mineralogy, and agrochemistry, 3 figures, 2 references.
The radiation-induced consequences of the Chemobyl disaster have now been thoroughly investigated with respect to its effects on the health of the population and the state of the environment. Another purpose is to create biological models capable of predicting the effects of low irradiation doses on the human organism. Using trace amounts of radionuclides, we may follow with high precision the pathways of distribution of the labeled compounds and their metabolites between organs and tissues, determine the sites of their accumulation, and provide methods for their elimination from the organism. In this context, data on the distribution of drugs, belonging to different classes, in the organism against a background of low doses of ionizing radiation may serve, on the one hand, as a probe in studying the mechanisms of action of the radiation and, on the other hand, as a basis for correcting the therapeutic schedules and schemes of drug administration. The purpose of this work was to establish the laws of variation of the parameters of drug pharmacokinetics in experimental animals after preliminary total irradiation at relatively low doses.