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Objective: Previously, low-dose radiation therapy was used for pneumonia treatment. We aimed to investigate the safety and effectiveness of carbon nanoparticles labeled with Technetium isotope (99mTc) in a form of ultradispersed aerosol in combination with standard COVID-19 therapy. The study was a randomized phase 1 and phase 2 clinical trial of low-dose radionuclide inhalation therapy for patients with COVID-19 related pneumonia. Method: We enrolled 47 patients with confirmed COVID-19 infection and early laboratory signs of cytokine storm and randomized them into the Treatment and Control groups. We analyzed blood parameters reflecting the COVID-19 severity and inflammatory response. Results: Low-dose 99mTc-labeled inhalation showed a minimal accumulation of radionuclide in lungs in healthy volunteers. We observed no significant differences between the groups before treatment in WBC-count, D-dimer, CRP, Ferritin or LDH levels. We found that Ferritin and LDH levels significantly raised after the 7th day follow-up only in the Control group (p < 0.0001 and p = 0.0005, respectively), while mean values of the same indicators did not change in patients in the Treatment group after the radionuclide treatment. D-dimer values also lowered in the radionuclide treated group, however, this effect was not statistically significant. Furthermore, we observed a significant decrease in CD19+ cell counts in patients of the radionuclide-treated group. Conclusion: Inhalation low-dose radionuclide therapy of 99mTc aerosol affects the major prognostic indicators of COVID-19- related pneumonia restraining inflammatory response. Overall, we identified no evidence of major adverse events in the group receiving radionuclide.

The aim of overview is to present the pooled data of published internal dose estimates and the results of corresponding analysis of internal irradiation features of experimental mice and rats after exposure to sprayed neutron activated radioactive 56MnO2. These dose estimates were conducted in a framework of multicenter international study to investigate biological effects as a result of exposure to sprayed radioactive 56MnO2 microparticles. Radionuclide 56Mn (T1/2 = 2.58 h) is one of the main gamma-beta emitters during the first hours after neutron activation of soil following nuclear explosion. It was concluded that there are three groups of organs of mice and rats, the radiation doses of which differ by approximately an order of magnitude: the group with the highest radiation doses (large and small intestine, stomach, skin and lungs), the group with lowered radiation doses (eyes, esophagus, trachea), the group with the lowest radiation doses (liver, heart, kidneys). The radiation doses to organs are proportional to the activity of the sprayed radioactive powder. The distribution of internal radiation doses among organs of experimental mice of different strains but of the same age was practically the same in case of exposure to the same activity of sprayed 56MnO2 powder. Doses of internal irradiation of experimental mice substantially exceed the doses of internal irradiation of experimental rats exposed to the same activities of the sprayed 56MnO2 powder. The data presented in the overview can be helpful for further investigation and for interpretation of the biological effects of this type of irradiation.

The problem of differentiating between primary irradiation and exposure due to residual radioactivity following A-bombing (including beta-exposure), is the subject of special attention and discussions in order to understand the health effects following the Hiroshima and Nagasaki A-bombings, especially among newcomers to cities soon after the detonations. In this work, the method of single quartz grain luminescence retrospective dosimetry was applied for a retrospective estimation of the ‘dose-depth’ profile in a quartz-containing tile extracted from the building of former Hiroshima University (HU), which was a ‘witness’ of the Hiroshima atomic bombing on the 6 August 1945. It has been shown that results of retrospective estimates of the ‘dose-depth’ profile using the method of optically stimulated luminescence (OSL) from inclusions of quartz grains in very thin layers of the sample, in combination with the calculations of the ‘dose-depth’ profile using the Monte Carlo method, indicates the possible presence of beta irradiation of thin layers of the sample located near the surface of the tile facing the air, where there is no electronic equilibrium from gamma radiation.

Estimates of external absorbed dose in experimental animals exposed to sprayed neutron-activated 56Mn powder are necessary for comparison with internal absorbed doses estimated under the same exposure conditions, which is required for a correct interpretation of the observed biological effects. It has been established that the measured dose of external absorbed dose as a result of gamma irradiation range 1–15 mGy, which is order of magnitude less than the maximal dose of internal gamma and beta irradiation of the whole body of the same experimental animals irradiated under the same conditions: according to the available literature data, the maximal values ​​of absorbed dose of internal gamma-beta irradiation of the whole body are in the range of 330 mGy–1200 mGy for mice and 100 mGy–150 mGy for rats. It is concluded that under the conditions of experiments with dispersed neutron-activated powder 56MnO2, internal gamma-beta irradiation of experimental animals is the main factor of radiation exposure compared to external gamma irradiation.

Manganese-56 (56Mn) was one of the dominant neutron-activated radionuclides during the first hours following the atomic-bombing of Hiroshima and Nagasaki. The radiation spectrum of 56Mn and the radiation emission from excited levels of 56Fe following 56Mn beta-decay include gamma-quanta, beta-particles, Auger electrons and X-rays. The dispersion of neutron activated 56Mn in the air can lead to entering of radioactive microparticles into the lungs. The investigation of spatial microdistribution of an internal dose in biological tissue exposed to 56Mn is an important matter with regards to the possible elevated irradiation of the lung alveoli and alveolar ducts. The Monte Carlo code (MCNP-4C) was used for the calculation of absorbed doses in biological tissue around 56Mn dioxide microparticles. The estimated absorbed dose has a very essential gradient in the epithelium cells of lung alveoli and alveolar duct: from 61 mGy/decay on the surface of simple squamous cells of epithelium to 0.15 mGy/decay at distance of 0.3 μm, which is maximal cell thickness. It has been concluded that epithelial cells of these pulmonary microstructures are selectively irradiated by low-energy electrons: short-range component of beta-particles spectrum and Auger electrons. The data obtained are important for the interpretation of biological experiments implementing dispersed neutron-activated 56Mn dioxide powder.

Skin cancer is the most frequently diagnosed type of cancer among all malignant neoplasms. The decrease in mitotic activity and the death of intact keratinocytes arise due to the constantly renewing epithelium is highly sensitive to ionising radiation. Objective: immunohistochemical evaluation of the proliferative-apoptotic balance of keratinocytes, the fibrous component of the skin and the expression of pro-inflammatory and anti-inflammatory cytokines after single or fractional local electron irradiation. Methods. Wistar rats (n=50) were taken and divided into groups: I – control (n=20), which were injected with saline; and experimental groups, local electron irradiation at doses: II – 8 Gy (n=10; single), III – 40 Gy (n=10, single), IV – summary dose 78 Gy (n=10; fractional; 13 Gy per day for 6 days). Results and Conclusions. 8 Gy and 40 Gy single local electron irradiation leads to a shift in the proliferative-apoptotic balance of keratinocytes towards their apoptosis, the activity of which is directly correlate with the dose of ionizing radiation, and 78 Gy summary dose in fractions leads to partial desquamation of the epithelium and inflammatory infiltration. In addition, a significant increase in the expression of type I and type III collagen fibers and the development of signs of radiation-induced skin fibrosis takes place against the background of 78 Gy fractional local electron irradiation. At the same time, after single 8 Gy and 40 Gy electron irradiation the described immunohistochemical changes were insignificant and directly correlated with the dose of ionizing radiation.

Insufficient vascular growth in the area of artificial-material implantation contributes to ischemia, fibrosis, the development of bacterial infections, and tissue necrosis around the graft. The purpose of this study was to evaluate angiogenesis after implantation of polycaprolactone microfiber scaffolds modified by a pCMV-VEGF165-plasmid in rats. Influence of vascularization on scaffold degradation was also examined. We investigated flat microfibrous scaffolds obtained by electrospinning polycaprolactone with incorporation of the pCMV-VEGF-165 plasmid into the microfibers at concentrations of 0.005 ng of plasmid per 1 mg of polycaprolactone (0.005 ng/mg) (LCGroup) and 0.05 ng/mg (HCGroup). The samples were subcutaneously implanted in the interscapular area of rats. On days 7, 16, 33, 46, and 64, the scaffolds were removed, and a histological study with a morphometric evaluation of the density and diameter of the vessels and microfiber diameter was performed. The number of vessels was increased in all groups, as well as the resorption of the scaffold. On day 33, the vascular density in the HCGroup was 42% higher compared to the control group (p = 0.0344). The dose-dependent effect of the pCMV-VEGF165-plasmid was confirmed by enhanced angiogenesis in the HCGroup compared to the LCGroup on day 33 (p-value = 0.0259). We did not find a statistically significant correlation between scaffold degradation rate and vessel growth (the Pearson correlation coefficient was ρ = 0.20, p-value = 0.6134). Functionalization of polycaprolactone by incorporation of the pCMV-VEGF165 plasmid provided improved vascularization within 33 days after implantation, however, vessel growth did not seem to correlate with scaffold degradation rate.

Individual retrospective dosimetry was developed at A. Tsyb Medical Radiological Research Centre (A. Tsyb MRRC) after the Chernobyl accident for assessment and analysis of radiation effects on people lived in radioactively contaminated settlements in the Kaluga and Bryansk regions. The method was also used in radiation epidemiology case-control studies within frames of international pilot projects. The ob-tained data demonstrated reliable dose-response relationship for thyroid cancer in patients with diag-nosed thyroid cancer, who were children and adolescents at the time of the accident and resided in radi-oactively contaminated areas in the Bryansk region. The dose-response relationship for diagnosed inva-sive breast cancer was found in women, resided in radioactively contaminated settlements since the acci-dent till the first diagnosis of cancer that was established within the period from October 2008 to February 2013. Their age at diagnosis was under 55 years. At the same time, no dose-response relationship for leu-kaemia was found in children under 5 years old at the time of the accident. The individual retrospective dosimetry method has been updated and used in pilot studies for verifying conservative estimates of radi-ation doses to the population exposed to radiation as a result of nuclear tests at the Semipalatinsk nuclear test site, as well as for verifying estimates of external radiation doses to people affected by the accident at the Fukushima Daiichi NPP. The method was also used for estimating individual doses from residual radi-oactivity for the survivors of the Hiroshima and Nagasaki atomic bombings. The long-term collaboration continues under bilateral International Collaboration Agreements between the National Medical Research Radiological Centre and leading research centres in the Republic of Kazakhstan and Japan. Since 2016 researchers and physicians of A. Tsyb MRRC have modi-fied method of stimulated luminescence of natural and synthetic materials and developed innovative technology in vivo dosimetry that has been put into clinical practice for estimating spatial radiation doses distribution in internal organs at risk during the brachytherapy of prostate cancer, gynecologic and recur-rent pelvic tumors, as well as for estimating local radiation dose to the skin of the breast gland with the tumor. The 35-year experience in the development and application of methods for individual retrospective dosimetry after the Chernobyl accident formed the basis for identifying future-pointing trends for the de-velopment of novel applications of stimulated luminescence techniques. Radiation-induced stimulated luminescence dosimetry can be applicable in uncontrolled radiation events; retrospective dosimetry method applicable for neutron beam radiation therapy is under development. The method of in vivo do-simetry is useful in radiation oncology. Now assembled thermoluminiscent micro-sized dosimeters are used for arterial radioembolization. At present, feasibility of using items of clothing and special inserts (buttons, fastenings, etc.), parts of wearable electronic devices as natural dosimeters, as well as the feasi-bility of using luminescent microdosimeters, made of different materials, after exposure to high LET radiation ranged from a fraction of mGy to the dose greater than 60 Gy have been examined. Development of flexible planar microdosimeter assemblies in order to obtain more detailed information about possible discrepancy in distribution of planned and actual radia-tion doses to patients during radiotherapy is considered.

The experiment was performed in support of a Japanese initiative to investigate the biological effects of irradiation from residual neutron-activated radioactivity that resulted from the A-bombing. Radionuclide 56Mn (T1/2 = 2.58 h) is one of the main neutron-activated emitters during the first hours after neutron activation of soil dust particles. In our previous studies (2016–2017) related to irradiation of male Wistar rats after dispersion of 56MnO2 powder, the internal doses in rats were found to be very inhomogeneous: distribution of doses among different organs ranged from 1.3 Gy in small intestine to less than 0.0015 Gy in some of the other organs. Internal doses in the lungs ranged from 0.03 to 0.1 Gy. The essential pathological changes were found in lung tissue of rats despite a low level of irradiation. In the present study, the dosimetry investigations were extended: internal doses in experimental mice and rats were estimated for various activity levels of dispersed neutron-activated 56MnO2 powder. The following findings were noted: (a) internal radiation doses in mice were several times higher in comparison with rats under similar conditions of exposure to 56MnO2 powder. (b) When 2.74 × 108 Bq of 56MnO2 powder was dispersed over mice, doses of internal irradiation ranged from 0.81 to 4.5 Gy in the gastrointestinal tract (small intestine, stomach, large intestine), from 0.096 to 0.14 Gy in lungs, and doses in skin and eyes ranged from 0.29 to 0.42 Gy and from 0.12 to 0.16 Gy, respectively. Internal radiation doses in other organs of mice were much lower. (c) Internal radiation doses were significantly lower in organs of rats with the same activity of exposure to 56MnO2 powder (2.74 × 108 Bq): 0.09, 0.17, 0.29, and 0.025 Gy in stomach, small intestine, large intestine, and lungs, respectively. (d) Doses of internal irradiation in organs of rats and mice were two to four times higher when they were exposed to 8.0 × 108 Bq of 56MnO2 (in comparison with exposure to 2.74 × 108 Bq of 56MnO2). (e) Internal radiation doses in organs of mice were 7–14 times lower with the lowest 56MnO2 amount (8.0 × 107 Bq) in comparison with the highest amount, 8.0 × 108 Bq, of dispersed 56MnO2 powder. The data obtained will be used for interpretation of biological effects in experimental mice and rats that result from dispersion of various levels of neutron-activated 56MnO2 powder, which is the subject of separate studies.

Electron spin resonance (ESR) dosimetry was applied to human tooth enamel in order to obtain individual absorbed doses for victims of the Hiroshima bomb who lived in the ‘black rain’ area. The so-called ‘black rain’ fell in the form of precipitation on the western part of Hiroshima city and the northwestern suburbs within a few hours after the explosion of the atomic bomb on 6 August 1945, and exposed the population in this area. Only three tooth samples were collected from this area. Since the teeth were located at positions 1, 2 and 4, only the lingual portion was used for the analysis. The results showed that the excess dose after subtracting natural radiation for one (position 4; hh1) was background, for the second (position 2; hh2) it was 133 mGy, and for the other (position 1; hh3) it was 243 mGy. Based on these results, we further investigated the radiation dose attributed to dental X-rays and head CT scan. Such dose of the hh3 radiographic examination was estimated to be 57–160 mGy, which implies an additional exposure around 135 mGy after subtraction. On the other hand, the dose data of hh1 after subtracting dental X-rays was negative. This may mean that such additional doses are an overestimation. In addition, the effect of sunlight should be considered, which is the same direction of overestimation. As a result, the residual dose of 140 mGy suggests the inclusion of radiation from the ‘black rain.’

The experiment was performed in support of a Japanese initiative to investigate the biological effects of irradiation from residual neutron-activated radioactivity that resulted from the A-bombing. Radionuclide 56Mn (T1/2 = 2.58 h) is one of the main neutron-activated emitters during the first hours after neutron activation of soil dust particles. In our previous studies (2016–2017) related to irradiation of male Wistar rats after dispersion of 56MnO2 powder, the internal doses in rats were found to be very inhomogeneous: distribution of doses among different organs ranged from 1.3 Gy in small intestine to less than 0.0015 Gy in some of the other organs. Internal doses in the lungs ranged from 0.03 to 0.1 Gy. The essential pathological changes were found in lung tissue of rats despite a low level of irradiation. In the present study, the dosimetry investigations were extended: internal doses in experimental mice and rats were estimated for various activity levels of dispersed neutron-activated 56MnO2 powder. The following findings were noted: (a) internal radiation doses in mice were several times higher in comparison with rats under similar conditions of exposure to 56MnO2 powder. (b) When 2.74 × 108 Bq of 56MnO2 powder was dispersed over mice, doses of internal irradiation ranged from 0.81 to 4.5 Gy in the gastrointestinal tract (small intestine, stomach, large intestine), from 0.096 to 0.14 Gy in lungs, and doses in skin and eyes ranged from 0.29 to 0.42 Gy and from 0.12 to 0.16 Gy, respectively. Internal radiation doses in other organs of mice were much lower. (c) Internal radiation doses were significantly lower in organs of rats with the same activity of exposure to 56MnO2 powder (2.74 × 108 Bq): 0.09, 0.17, 0.29, and 0.025 Gy in stomach, small intestine, large intestine, and lungs, respectively. (d) Doses of internal irradiation in organs of rats and mice were two to four times higher when they were exposed to 8.0 × 108 Bq of 56MnO2 (in comparison with exposure to 2.74 × 108 Bq of 56MnO2). (e) Internal radiation doses in organs of mice were 7–14 times lower with the lowest 56MnO2 amount (8.0 × 107 Bq) in comparison with the highest amount, 8.0 × 108 Bq, of dispersed 56MnO2 powder. The data obtained will be used for interpretation of biological effects in experimental mice and rats that result from dispersion of various levels of neutron-activated 56MnO2 powder, which is the subject of separate studies.

DNA double-strand breaks (DSB) are among the most harmful DNA lesions induced by ionizing radiation (IR). Although the induction and repair of radiation-induced DSB is well studied for acute irradiation, responses to DSB produced by chronic IR exposures are poorly understood, especially in human stem cells. The aim of this study was to examine the formation of DSB markers (γH2AX and phosphorylated kinase ATM, pATM, foci) in human mesenchymal stem cells (MSCs) exposed to chronic gamma-radiation (0.1 mGy/min) in comparison with acute irradiation (30 mGy/min) at cumulative doses of 30, 100, 160, 240 and 300 mGy. A linear dose-dependent increase in the number of both γH2AX and pATM foci, as well as co-localized γH2AX/pATM foci (“true” DSB), were observed after an acute radiation exposure. In contrast, the response of MSCs to a chronic low dose-rate IR exposure deviated from linearity towards a threshold model, for γH2AX, pATM foci and γH2AX/pATM foci, with an indication of a “plateau”. The state of equilibrium between newly formed DSB at a low rate during the protracted exposure time and the elimination of a fraction of DSB is proposed as a mechanistic explanation of the non-linear DSB responses following a low dose-rate irradiation. This notion is supported by the observation of the elimination of a substantial fraction of DSB 6 h after the cessation of the exposures. Our results demonstrate non-linear dose responses for γH2AX and pATM foci in human MSCs exposed to low dose-rate IR and showed the existence of a threshold, which may have implications for radiation protection in humans.