Purpose: The study explores the possibility of manufacturing radiation sources for personalized brachytherapy using titanium alloys, activated in a neutron flux reactor, by measuring the radiation composition of applicator implants and their dosimetric characteristics. Material and methods: A 3D implant of a brachytherapy source was made from a titanium alloy using an additive selective laser melting setup. The titanium 3D prototype was irradiated for three days in the horizontal experimental channel of the IR-8 reactor. Subsequently, measurements of the gamma-ray spectrum from the irradiated implant were carried out on a spectrometer, and dose characteristics of the 3D implant were measured using a dosimeter-radiometer. Results: In the experimental 3D implant obtained by us, the radionuclide 47Sc exhibits the highest activity. Currently, 47Sc is considered a promising candidate for brachytherapy. It possesses attractive nuclear and physical properties as a β-emitter, decaying into the ground state (27 %) of 47Ti (Eβmax = 600 keV) and the excited state of 47Ti (Eβmax = 439 keV) with a half-life of 3.4 days. Additionally, 47Sc emits γ-radiation at an energy of 159 keV (68 %), which is suitable for imaging, allowing for SPECT or planar scintigraphy and obtaining a picture of the drug’s distribution in the body. In the experimental implant, small amounts of scandium radionuclides – 46Sc and 48Sc, were also detected, emitting sufficiently hard gamma radiation, which can pose a problem for patient dosage determination. The advantages of using titanium-47 with an enrichment of over 95 %, economically available, have been demonstrated, allowing for high radiochemical yields of 47Sc, sufficient for therapy. Conclusion: The 3D printing technology allows the production of a customized applicator for brachytherapy of specific dimensions and the delivery of arbitrarily-shaped sources to the tumor area for personalized therapy of oncological diseases. When implanting sources based on titanium alloys activated in a neutron flux of a research nuclear reactor, the radionuclide scandium-47 exhibits the highest activity.
Metastasis is one of the main causes of relapse and subsequent high mortality from cancer. Metastases can contain very few cells and spread throughout the body. Despite the existing variety of diagnostic imaging methods, in practice, the resolution of note of them allows unambiguously diagnosing the presence of a tumor (clump of cancer cells) smaller than 1–2 mm in size. After surgery and tumor removal, patients are typically offered chemotherapy, external beam radiation therapy, or α - or β -emitter radionuclide therapy. This therapy has side effects that lead to additional risks and may interfere with continued treatment. Recently, a number of works, in contrast to the traditional approach, have proposed using short-range radionuclides instead of α - or β -emitters [1–3]. It is convenient to use Auger or conversion electron emitters as short-acting therapeutic agents. Auger electrons and conversion electrons have a short range and high specific linear energy loss in biological tissue: they are capable of damaging cells within a few tens of microns, but do not have a radiotoxic effect over long distances, without damaging healthy cells and tissues. The most efficient and convenient Auger and conversion electron emitters for practical use include ^103m Rh ( T_1/2=56.1 min), which has the lowest ratio of the number of γ quanta to electrons [1] and can be obtained by a generator method. The predecessors of ^103m Rh ( T_1/2=56.1 min) in the generator can be ^103 Ru ( T_1/2=39.247 days) or ^103 Pd ( T_1/2=16.99 days). In order to clarify the prospects for producing these precursors, we have measured the rates of ^102 Ru( n,γ ) ^103 Ru and ^102 Pd( n,γ ) ^103 Pd reactions upon neutron irradiation of metal ruthenium of natural isotopic composition and metal palladium, enriched in the ^102 Pd isotope to 96.36 % , in a horizontal experimental channel of the IR-8 reactor.
Metastasis is one of the main causes of relapse and subsequent high mortality from cancer. Metastases can contain very few cells and spread throughout the body. Despite the existing variety of diagnostic imaging methods, in practice, the resolution of none of them allows one to unambiguously diagnose the presence of a tumor (clump of cancer cells) smaller than 1–2 mm in size. After surgery and tumor removal, patients are typically offered chemotherapy, external beam radiation therapy, or α- or β-emitter radionuclide therapy. This therapy has side effects that lead to additional risks and may interfere with continued treatment. Recently, a number of works, in contrast to the traditional approach, have proposed using “short-range” radionuclides instead of α- or β-emitters [1–3]. It is convenient to use Auger or conversion electron emitters as “short-acting” therapeutic agents. Auger electrons and conversion electrons have a short range and high specific linear energy loss in biological tissue; they are capable of damaging cells within a few tens of microns, but do not have a radiotoxic effect over l ng distances, without damaging healthy cells and tissues. The most efficient and convenient Auger and conversion electron emitters for practical use include 103mRh (𝑇1/2 = = 56.1 min), which has the lowest ratio of the number of γ quanta to electrons [1] and can be obtained by a generator method. The predecessors of 103mRh (𝑇1/2 = 56.1 min) in the generator can be 103Ru (𝑇1/2 = = 39.247 days) or 103Pd (𝑇1/2 = 16.99 days). In order to clarify the prospects for producing these precursors, we have measured the rates of reactions 102Ru(𝑛, γ)103Ru and 102Pd(𝑛, γ)103Pd upon neutron irradiation of metal ruthenium of natural isotopic composition and metal palladium, enriched in the 102Pd isotope to 96.36%, in a horizontal experimental channel of the IR-8 reactor.
Purpose: To investigate the effect of γ, n-irradiation of the mice head on the brain cells damage, behavior and cognition, and to examine the possibility of using lactoferrin (LF) to alleviate radiation-induced impairments. Material and methods: Mice heads were irradiated in a beam of neutrons and gamma rays from the IR-8 nuclear reactor. The brain cells of control and irradiated mice were isolated using Percoll. Neurons and resting and activated microglia cells were analyzed using the fluorescently labeled antibodies and flow cytometry. The level of DNA double-strand breaks in neurons was determined by γH2AX histone content. Cytokine gene expression in the hippocampus was studied by RT-PCR. Behavior and cognitive functions were studied using the open field, Morris water maze and novel object recognition tests. LF was isolated from female colostrum by preparative ion-exchange chromatography and purified by affinity chromatography on heparin-sepharose. Results: γ, n-Irradiation of the mice head at a dose of 1.5 Gy led to an increase in the level of DNA double-strand breaks in neurons. Twenty-four hours after irradiation the total number of cells and the number of neurons in the isolated fraction of brain cells decreased, but the number of microglial cells remained unchanged. The number of resting and activated microglia did not change within 3–72 h after γ, n-irradiation. The expression level of the TNFα, IL-1β, and IL-6 genes increased 2 months after γ, n-irradiation of the mice head at a dose of 1.5 Gy, indicating the development of neuroinflammation. At this time, irradiated mice demonstrated the anxiety-like behavior and impaired spatial and recognition memory. A single i.p. administration of human LF to mice immediately after γ, n-irradiation of the head did not affect the observed radiation-induced disturbances, but decreased the gene expression levels of TNFα, IL-1β and IL-6 pro-inflammatory cytokines and increased the gene expression level of TGFβ anti-inflammatory cytokine in the hippocampus 2 months after radiation exposure. The obtained results indicate a partial decrease in the level of hippocampal neuroinflammation of irradiated animals treated with LF. Conclusion: γ, n-Irradiation of the mice head at a dose of 1.5 Gy leads to DNA damage of neurons and the decrease in the number of neurons. Microglia cells are more resistant to such radiation exposure. Late after head-only γ, n-irradiation, mice develop neuroinflammation, which is detected by an increase in the pro-inflammatory cytokine gene expression in the hippocampus and also by anxiety-like behavior and impaired cognitive functions. A single LF administration leads to a partial decrease in the neuroinflammation level, but does not affect the other studied parameters. The optimal dosing regimen of LF remains to be determined to preserve cognitive functions after γ, n-irradiation of the brain.
Metastasis is one of the main causes of relapse and subsequent high mortality from cancer. Metastases can contain very few cells and spread throughout the body. Despite the existing variety of diagnostic imaging methods, in practice, the resolution of note of them allows unambiguously diagnosing the presence of a tumor (clump of cancer cells) smaller than 1-2 mm in size. After surgery and tumor removal, patients are typically offered chemotherapy, external beam radiation therapy, or alpha-or beta-emitterradionuclide therapy. This therapy has side effects that lead to additional risks and may interfere with continued treatment. Recently, a number of works, in contrast to the traditional approach, have proposed using short-range radionuclides instead of alpha-or beta-emitters [1-3]. It is convenient to use Auger or conversion electron emitters as short-acting therapeutic agents. Auger electrons and conversion electrons have a short range and high specific linear energy loss in biological tissue: they are capable of damaging cells within a few tens of microns, but do not have a radiotoxic effect over long distances, without damaging healthy cells and tissues. The most efficient and convenient Auger and conversion electron emitters for practical use include (103)mRh (T-1/2 =56.1min), which has the lowest ratio of the number of gamma quanta to electrons [1] and can be obtained by a generator method. The predecessors of (103)mRh (T-1/2=56.1min) in the generator can be Ru-103 (T-1/2 =39.247days) or(103)Pd (T-1/2 =16.99days). In order toclarify the prospects for producing these precursors, we have measured the rates of Ru-102(n, gamma)Ru-103 and Pd-102(n, gamma)103Pd reactions upon neutron irradiation of metal ruthenium of natural isotopic composition and metal palladium, enriched in the Pd-102 isotope to 96.36%, in a horizontal experimental channel of theIR-8 reactor.
The paper describes the experimental technique and presents data obtained when measuring the flux of monochromatic neutrons in the sample position at installations located on the horizontal experimental channels of the IR-8 reactor (NRC Kurchatov Institute) and used in research in the field of condensed matter physics and materials science.
Aim: Cancer stem cells (CSCs) are highly resistant to chemotherapy and γ-irradiation. Neutrons have a high linear energy transfer, which can lead to extensive damage to the DNA of tumor cells and CSCs. The aim of this work was to compare the sensitivity of MCF-7 human breast adenocarcinoma cells and CSCs to γ- and γ,n-irradiation. Methods: To increase the number of CSCs, MCF-7 cells were cultured as mammospheres. γ-irradiation was carried out in a GUT-200M device (60Co source) in the dose range of 1-8 Gy at a dose rate of 0.75 Gy/min. γ,n-irradiation was carried out in an IR-8 reactor in the dose range of 0.05-2 Gy at a dose rate of 0.06 Gy/min. DNA DSB formation was assessed by the level of γH2AX foci using fluorescence microscopy and flow cytometry. CSCs were identified by flow cytometry as CD44+/CD24-/low cells. Results: We showed that γ,n-irradiation induced the formation of γH2AX foci of a larger size than did γ-irradiation and led to more severe DNA damage per 1 Gy. Moreover, γ,n-radiation was found to have a high relative biological effectiveness (RBE) as assessed by the cell survival rate, the number of CSCs in culture, and the ability of CSCs to repopulate. The highest RBE of neutron radiation was observed at low doses, when cell survival rate decreased by only 5%-10%. With an increase in the radiation dose, the RBE value decreased for all studied parameters, but it remained as high as 5. Conclusion: γ,n-radiation is highly effective against CSCs. Our results explain the efficacy of neutron therapy for resistant forms of breast cancer.
Purpose: In recent years, a growing number of studies have focused on the mechanisms of action of densely ionizing radiation. This is associated with the development of radiation therapy of tumors using accelerated ions. The use of densely ionizing radiation appears to be the most promising method, optimal for treating patients with severe radioresistant forms, such as widespread head and neck tumors, recurrent and metastatic tumors, and some forms of brain tumors. The goal of our study was to investigate the effects of gamma-neutron radiation on mouse neural stem/progenitor cells (NSCs/NPCs). Methods: NSCs/NPCs were isolated from neonatal mouse brains. Cells were irradiated in a collimated beam of neutrons and gamma rays of the IR-8 nuclear reactor. At 5 and 7 days after irradiation, cells and neurospheres were counted to assess survival. The number of DNA double-strand breaks and their repair efficiency were determined by immunocytochemical gamma H2AX staining followed by counting the number of gamma H2AX foci using a fluorescent microscope. Results: We observed a dose-dependent decrease in the survival of NSCs/NPCs after irradiation at doses above 100 mGy and stimulation of the proliferation of these cells at doses of 25 and 50 mGy. In terms of a decrease in cell survival, the effect of gamma-neutron irradiation significantly exceeded the effect of gamma irradiation: the maximum value of the relative biological efficiency for gamma-neutron irradiation comprised 9.7. Gamma-neutron irradiation led to the formation of double-strand DNA breaks detected by the formation of foci of histone gamma H2AX in the cell nuclei. The gamma H2AX foci formed after gamma-neutron irradiation of NSCs/NPCs at doses of 100-500 mGy were characterized by a larger size in comparison with foci induced by gamma irradiation and gamma-neutron irradiation at a dose of 50 mGy. The repair of double-strand DNA breaks induced by gamma,n-irradiation was slow; the repair rate depended on the radiation dose. Conclusions: The data obtained indicate high sensitivity of proliferating NSCs/NPCs to gamma-neutron radiation. High RBE of gamma-neutron radiation requires special measures to protect the neurogenic regions of the brain when using this type of radiation in radiation therapy.
ABSTRACТPurpose: To explore if the total body γ-irradiation at a dose of 0.1 Gy 7 days prior to acute mixed γ, n-irradiation of the head at the dose of 1 Gy can reduce the harmful effects of neutron irradiation on the hippocampal functions, neuroinflammation and neurogenesis.Materials and methods: Mice were exposed to γ-radiation alone, mixed γ,n-radiation or combined γ-rays and γ,n-radiation 7 days after γ-irradiation. Two months post-irradiation, mice were tested in Open Field and in the Morris water maze. The content of microglia, astrocytes, proliferating cells and cytokines TGF-β, TNF-α, IL-1β, GFAP levels, hippocampal BDNF, NT-3, NT-4, NGF mRNA expression were evaluated.Results: Two months after combined irradiation, we observed impaired hippocampus-dependent cognition, which was not detected in mice exposed to γ,n-irradiation. Combined exposure and γ,n-irradiation led to a significant increase in the level of activated microglia and astrocytes in the brains. The level of pro- and anti-inflammatory cytokines in the brain and hippocampal neurotrophine's genes changed differenly after the combined exposure and γ,n-irradiation. The quantity of DCX-positive cells was reduced after γ,n-irradiation exposer alone, but increased after combined irradiation.Conclusions: Our results indicate radio-adaptive responses in brains of mice that were exposed to low-dose gamma irradiation 7 days prior to acute 1 Gy γ,n-irradiation.
Определение поглощенной в биологическом образце дозы при смешанном гамма-нейтронном облучении
A method is proposed and results on determination of absorbed doses under mixed gamma–neutron irradiation of biological samples on a horizontal channel of the IR-8 research reactor at the National Research Center Kurchatov Institute are presented.
Experimental data have been presented for the spatial deflection and energy profiling of reactor neutron beams using flexible polyvinylchloride tubes, the inner surfaces of which are covered by a liquid fluoropolymer thin film.
В работах [1-2] было обнаружено исключительно высокое пропускание ультрахолодных нейтронов (УХН) полихлорвиниловыми трубками промышленного производства.Полихлорвинил (ПВХ) представляет собой высокомолекулярный полимер (СН 2 -CHСl) n с высоким молекулярным весом молекул в пределах от 30 000 до 100 000 amu. Граничная скорость полихлорвинила V lim = 2.9 m/s, поэтому нейтроны, падающие на гладкую поверхность с нормальной компонентой скорости V n < V lim , зеркально отражаются.Величину V lim можно увеличить, если на поверхность полихлорвинила нанести тонкий (∼ 10 µm) слой вещества, обладающего более высокой граничной скоростью, но сохраняющего зеркальность поверхности.В качестве такого покрытия
The properties of a convergent neutron lens in the form of an assembly of bent glass capillaries have been experimentally investigated. Each capillary is a conical tube with a length of 22.5 cm, an entrance diameter of 0.25 mm, and an exit diameter of 0.17 mm. The spectrum of thermal neutrons incident on the lens entry is formed on the beam of the IR-8 reactor by means of a diamond microcrystalline filter and investigated with a time-of-flight spectrometer. The spatial distribution of the neutron beam at the exit from the lens is measured using the position-sensitive image plate detector. The measured focal length of the lens is 75–80 mm. The possibility of focusing neutrons with an increase in the local beam density at the lens axis by a factor of 4.9 is demonstrated.
We describe an experimental installation for a new test of the weak equivalence principle for neutron. The device is a sensitive gravitational spectrometer for ultracold neutrons allowing to precisely compare the gain in kinetic energy of free falling neutrons to quanta of energy h Omega transferred to the neutron via a non stationary device, i.e, a quantum modulatorThe results of first test experiments indicate a collection rate allowing measurements of the factor of equivalence gamma with a statistical uncertainty in the order of 5 x 10(-3) per day. A number of systematic effects were found, which partially can be easily corrected. For the elimination of others more detailed investigations and analysis are needed. Some possibilities to improve the device are also discussed. (C) 2015 Elsevier B.V. All rights reserved.
Показана возможность транспортировки, отклонения и оптимизации пучков тепловых нейтронов при помощи гибких полихлорвиниловых трубок с внутренним фторполимерным покрытием. Приведены результаты экспериментальных исследований по транспортировке тепловых нейтронов с помощью прямых и изогнутых трубок.
We present estimations of systematic corrections and results of their experimental studies for our neutron lifetime experiment carried out in 2008–2010 at ILL. Taking into account these systematic corrections, we reduce the data of three independent sets of measurements (obtained during period 2008–2010) performed with different energy spectra of ultracold neutrons (UCNs) at different trap temperatures to the mean neutron lifetime value equal to 880.2(1.2) s.
The possibility of transporting, deflecting, and optimizing thermal neutron beams using flexible polyvinyl chloride tubes with internal fluorine polymer coating is demonstrated. Experimental results on transportation of thermal neutrons using straight and bent tubes are presented.