Volume 70, Nº 3 (2025)
Radiation Biology
Study of the Efficacy of Cell Therapy for Severe Local Radiation Injuries in the Use of Drugs Affecting the State of Irradiated Tissues Before Cell Transplantation
Resumo
Purpose: To study the possibility of enhancing the therapeutic efficacy of multipotent mesenchymal stromal cells (MMSC) or stromal vascular fraction (SVF) cells in the treatment of severe local radiation injuries under the conditions of the use of pharmacological drugs, the use of which before and after cell transplantation can improve the condition of the irradiated tissue and thereby create favorable conditions for engraftment and functioning of the injected cells.
Material and methods: The work was carried out on male rats of the Wistar–Kyoto inbred line weighing 260–280 g. The animals were locally irradiated in the iliolumbar region of the back on an X-ray machine LNK-268 (RAP 100–10) at a dose of 110 Gy (voltage on the tube 30 kV, current 6.1 mA, Al filter with a thickness of 0.1 mm), at a dose rate of 20.0 Gy/min. The area of the irradiation field was 8.5 cm2. The severity of radiation damage to the skin and the effects of treatment were assessed in dynamics by clinical manifestations and using planimetry. After exposure to radiation, rats developed radiation ulcers of the skin that did not heal for a long time (up to 3–4 months). Cell and drug therapy were carried out in different periods after irradiation: from the 28th to the 49th or from the 35th to the 56th day. As drugs affecting the condition of the affected tissues surrounding the formed radiation ulcer, a complex antibiotic levotetrasulfin forte and drugs that affect the microcirculation and trophism of irradiated tissues – pentoxifylline and detralex were used. For cell therapy, syngeneous MMSC or SVF cells were used. In the cell therapy setting, the drugs were administered for one week before the first cell transplant, one week between the first and second transplantation, and one week after the second cell transplant.
Results and Conclusion: It was shown that the administration of drugs or the use of cell therapy when used separately stimulated the healing of radiation ulcers. Moreover, the therapeutic effect of cell therapy is more pronounced than with the use of drugs. However, in combination with drug and cell therapy, no enhancing effect of pharmacological agents on the therapeutic efficacy of transplantation of MMSC or SVF cells of adipose tissue was noted. Thus, these experiments showed the possibility of successful use of a complex antibiotic in combination with drugs that improve blood supply and trophism of irradiated tissues in the treatment of severe local radiation injuries and the inability of drug therapy under these conditions to enhance the therapeutic effectiveness of cell therapy.
5-10
Post-Irradiation Changes in the Number of γH2AX and pATM Protein Foci in Human Mesenchymal Stem Cells Irradiated with 14.1 MeV Neutrons
Resumo
Purpose: Comparative analysis of dose-response dependences and kinetics of post-radiation changes in the number of γH2AX and pATM protein foci in human mesenchymal stem cells (MSCs) exposed to 14.1 MeV neutrons and cobalt-60 gamma-radiation.
Material and methods: The study used a primary culture of human MSCs obtained from the collection of BioloT LLC (Russia). The cells were irradiated using a neutron generator NG-14 (VNIIA, Russia), which provided neutron fluxes with an energy of 14.1 MeV, and a gamma-therapeutic device ROKUS-AM (JSC Ravenstvo, Russia; cobalt-60, dose rate 0.5 Gy/min) at doses of 0.1, 0.25 and 0.5 Gy. For quantitative assessment of γH2AX and pATM foci, immunocytochemical staining was done using antibodies to γH2AX and pATM, respectively. Statistical significance was assessed using analysis of variance (ANOVA).
Results: It was shown that the kinetics of post-radiation changes in the number of γH2AX foci in cells irradiated with neutrons is slower than after gamma irradiation. 24 h after irradiation with neutrons, ~ 62 % of γH2AX foci and ~ 52 % of pATM foci were recorded from their number 0.5 h after irradiation. These values were statistically significantly (p < 0.001) higher than the proportions of residual foci calculated after exposure to gamma-radiation: ~ 16 % and 6 %, respectively. The results obtained indicate that the proportion of complex, difficult-to-repair DNA damage in cells irradiated with neutrons is significantly higher than with gamma-radiation.
11-15
Protective Effect of Dimethylsulphoxide in Combination with Gluthathione and Cysteamine Against the Damaging Effect of Ionizing Radiation on Spermatogenesis
Resumo
Purpose: Experimental assessment of the radioprotective effect of dimethylsulfoxide in combination with glutathione and cysteamine on spermatogenesis in BALB/c mice under acute γ-irradiation.
Material and мethods:A single external γ-irradiation of male mice at a dose of 6 Gy was carried out on an IGUR installation (137Cs, dose rate 0.85 Gy/min).The timing of death of mice was recorded within 1 month. Animals 20 minutes before irradiation received an intraperitoneal injection of a mixture of dimethyl sulfoxide (4.5 g/kg), reduced glutathione (500 mg/kg) and cysteamine (150 mg/kg).The disturbance of spermatogenesis and its correction with a mixture of radioprotectors was assessed by quantitative indicators of spermatogenic cells and the morphofunctional state of sperm.
Results: In mice, on the 8th day after irradiation, the number of spermatogonia decreases (6 % of the control), on the 24th day – the number of spermatocytes, spermatids and spermatozoa – to 3.5 %, 6 % and 4.5 % of the control, respectively. The mixture of radioprotectors contributed to an increase in the number of spermatogonia up to 33 %, spermatocytes – up to 7 %, spermatids – up to 25 %, spermatozoa – up to 27 %.The viability coefficient (QC) of spermatogenic cells decreases on the 8th day after irradiation from 11.6 in the control to 8.0, on the 16th day – to 7.0, on the 24th day – to 6.0, on 32 1st and 62nd days – up to 5.0. When using radioprotectors, QoL on the 8th day corresponded to 10.0 and in subsequent periods was kept within 9.0.The number of epididymal spermatozoa decreases on the 24th day after irradiation to 80 %, on the 32nd day – to 60%, on the 62nd day – to 45 %. The mixture of radioprotectors contributed to an increase in the number of sperm to 95 % and 60 %, respectively).The number of live sperm decreases on the 32nd and 62nd days after irradiation and amounts to 35 % and 18 %, respectively, when using radioprotectors – 45 % and 30 %, respectively. On the 24th, 32nd and 62nd days after irradiation, the number of sperm with an abnormal head increases by 2 times. Radioprotectors reduce the number of sperm with an abnormal head by 1.5 times.
Conclusion: The data obtained indicate the protective effect of this mixture of radioprotectors on spermatogenesis and its possible use for the correction of spermatogenesis disorders when exposed to ionizing radiation. The mixture of protectors provides protection for 95 % of mice, with 65 % death in irradiated controls.
16-21
Biological Reactions under the Combined Action of Ionizing Radiation with Other Factors
Resumo
This review is devoted to the biological effects of combined exposure to ionizing radiation and factors of a different nature: temperature, non-ionizing radiation, various chemical agents, including heavy metals, immunogenic factors, emotional stress, etc. This effect is often called combined. If we are talking about the combined action of different types of ionizing radiation, for example, neutron and γ-radiation, then such an effect is called combined. The biological effects of the combined action of ionizing radiation and factors of a different nature have been studied by many authors, especially in the field of aerospace and military radiobiology. The review describes cases where the effect of the combined action of ionizing radiation and another factor is approximately equal to the sum of the effects from the action of these factors separately; these effects are called additive. The synergism of effects is described – an increase in the magnitude of the manifestation of effects with a combined action compared to their sum with separate exposure to the studied factors. Works devoted to the conditions for achieving synergistic effects and identifying those under which the degree of synergy will be maximum are analyzed. Cases of a decrease in the magnitude of effects under the combined influence of ionizing radiation and a factor of a different nature are shown in comparison with the effects observed when they act separately ‒ antagonism of effects. Understanding the mechanism of these phenomena is necessary for the successful development of radioprotective agents, the development of countermeasures in case of radiation accidents or the use of nuclear weapons, and the creation of effective means and methods of treating oncological diseases. The review also describes current problems in the use of radioprotectors.
22-33
Radiation Safety
Radiation Health Physics to Assure Radiation Safety and Protection of the Public and Personnel: Case Study of the SRC-FMBC
Resumo
Purpose: To describe, based on our original innovative developments, the role of radiation health physics in assuring radiation safety and protection of a) the public living near operating, decommissed and remediated radiation hazardous facilities and sites; and b) nuclear wor- kers .
Material and methods: The objects of the study included radiation hazardous facilities at different stages of the life cycle (operating, decommissioned, remediated), nuclear and uranium legacy sites, where samples of environmental and marine media (water, soil, vegetation, algae, bottom sediments) were collected, as well as local foodstuffs and drinking water. The samples were examined using dosimetric, radiometric, gamma-spectrometric and radiochemical methods. When studying the health status of the public living in the vicinity of these facilities, methods of radiation epidemiology were used, supplemented by our original innovative development of the health assessment.
Results: The conducted long-term studies allowed not only characterizing the facilities and sites under study, but also identification the features of the spatial and temporal distribution of radioactive materials including at the nuclear legacy sites. The presence of large volumes of artificially contaminated soils has been detected, which in some cases are classified as radioactive waste in terms of their activity values. It has been shown that man-made contamination spreads into ground waters as well as into local areas of coastal marine waters. The results of public health monitoring allow us to state that radiation hazardous facilities in Russia are operating safely. Five innovative hardware, methodological and dosimetric complexes have been created to support radiation safety of workers.
Conclusions: The radiation health physics is the radiation safety science developed by some generations of scientists and professionals of the SRC-FMBC. Today, this science helps to support the whole cycle of medical and health physics safety of nuclear workers and the public living in the areas affected by nuclear facilities – from the science based development to its implementation in practice.
The interdisciplinary approach implemented in the SRC-FMBC helps to comprehensively solve many difficult tasks of radiation safety and protection of the public and workers.
34-47
The Current State and Problems of Health Protection of Women Working in Conditions of Radiation Hazard
Resumo
Relevance: In the existing international radiation safety system (ICRP) and in national RSS - 99/2009, the main principle of protection is the exclusion of tissue and reduction of stochastic effects to an acceptable level. Particular attention is paid to the protection of the gonads, including for the purpose of protecting future generations. When calculating the risk and harm of cancer and hereditary diseases, coefficients with gender averaging are used, but it is recognized that there are significant differences in the values of radiation risk between men and women.
Purpose: To analyze the current state and problems of protecting the health of women working in radiation hazardous conditions.
Results: The analysis of the presented data on the current state of protection of the women’s health system aimed at protecting the unborn child does not fully meet the effectiveness of protecting the health of women working in high-tech production of new types of nuclear fuel and does not fully take into account new knowledge about non-chromosomal mutations as the second hereditary structure of the female body, which leads to the obvious conclusion: further study of the health parameters of workers in radiation hazardous industries and further improvement of measures to protect women’s health are required.
48-53
Analysis of the Radiation Situation in Aviation Flights under Conditions of Solar Proton Events
Resumo
With a general analysis of the levels of ionizing radiation characteristic of outer space and causing radiation hazard factors for astronauts, the issues of assessing the radiation situation in air travel also remain relevant. The purpose of the study was to analyze the types and characteristics of ionizing radiation in airspace up to heights of 20 km above the Ground and possible radiation doses to flight personnel during flights under these conditions. The composition of ionizing radiation and the energy characteristics of proton events are analyzed. The radiation dose rates are estimated depending on the altitude and geographical latitude of the flight. To minimize the exposure of flight personnel and radiation risks, it is important to systematically take into account the forecast of solar activity, altitude and latitude of flight, control the total flight time per year, radiation protection conditions and other factors.
54-69
Radiation Epidemiology
'Healthy Worker Effect' In Employees of Medical-Biological and Chemical Laboratories: Comparison with Effects in Nuclear Workers, in other Professional Contingents (Meta-Analyses), and the Role of the Radiation Factor
Resumo
Based on a search in a supported database of sources for standardized mortality ratio (SMR; compared with the general population) for all causes and all cancer mortality for various professions and types of employment, in PubMed, the Cochrane Library, Elibrary, through Google, Google Scholar and in the reference lists of found sources, a complete/representative sample of studies of SMR all causes and SMR all cancer for personnel of biomedical, agricultural, chemical and some other research laboratories (a total of 39 sources and 3 reviews) was formed. Meta-analyses performed on the basis of this sample demonstrated a high Healthy Worker Effect (HWE) for all causes for the total group of workers, for the group including biomedical, sanitary and agricultural laboratories, and for the group of chemists. SMR (±95 % confidence intervals) were, respectively: 0.63 (0.58; 0.68); 0.65 (0.57; 0.74) and 0.62 (0.56; 0.68). For SMR all cancer HWE, although of a smaller value, it was demonstrated for the first and second groups: 0.85 (95 % CI: 0.75; 0.96) and 0.78 (95 % CI: 0.70; 0.88), respectively. At the same time, for chemists, no excess in mortality from all cancers was noted either: 0.88 (95 % CI: 0.74; 1.05).
The HWE values for laboratory workers were compared with those for occupations characterized by the highest HWE values (cosmonauts/astronauts, athletes, pilots, nuclear workers, and the military; individual studies, meta- and pooled analyses). It was found that the scientific laboratory personnel had a HWE level for SMR all causes comparable to that of athletes and nuclear workers. However, the SMR all cancer index for laboratory researchers was significantly higher than in all comparison groups, with the exception of the military, which is obviously due to contacts with a variety of carcinogenic factors when working in laboratories.
Due to the absence of prerequisites for the formation of HWE characteristic of the compared contingents for the researchers, an assumption was made that the decrease in overall mortality among laboratory personnel may be primarily due to a scientific mindset, which allows them to better navigate the causal dependencies of life and more adequately prevent various consequences, rather than a special lifestyle, increased socioeconomic status and a decrease in the frequency of smoking (as some authors suggest).
Analysis of the influence of the radiation factor (external and internal irradiation) on the studied mortality rates for laboratory workers revealed some effects in relation to certain types of malignant neoplasms (leukemia, myeloma, lung cancer, bone cancer, etc.), but a number of them were not previously recognized as radiation-induced and their increase may be a consequence of the effect of other carcinogenic factors of work in chemical, biochemical, molecular biological and other laboratories.
70-82
Radiation Diagnostics
Using Machine Learning Algorithms to Detect Cancer Automatically
Resumo
The number of people diagnosed with cancer is growing all around the world. During the last twenty years, the overall cancer incidence in Iraq has doubled, leading to an increase in the number of diagnosed cancer fatalities. When it comes to deaths that occur in hospitals, cancer is the second-biggest cause. Therefore, a remedy to the issue should be an arrangement to decrease time waste, the right technique of directing the patient to notice symptoms, extremely accurate cancer detection, and a better monitoring system. The proposed method is an arrangement that lets and leads a patient to identify symptoms on their own, guiding them to a proper healthcare professional, correctly diagnosing cancer in its initial stages, and monitoring the patient throughout therapy. Currently, research into cancer detection systems only employs a single machine learning approach to identify cancer. The study that is being presented makes use of Convolutional Neural Networks (CNN), Random Forest, and the XGBoost Classifier, which are a machine learning algorithms that are applied to structured and tabular data in order to identify the existence of breast cancer, brain tumors, skin cancer, and lung cancer. These methods provide findings more quickly while also achieving a greater level of accuracy. Hosting this suggested solution in the cloud with a cutting-edge program will make it available to the public, providing an improved user experience and easier operation.
83-89
Radiation Therapy
Pathomorphological Changes in Cell Structures of Cerebral Metastasis of Lung Adenocarcinoma after Neoadjuvant Gamma Knife Radiosurgy. A Case Report
Resumo
Purpose: To identify and describe morphological changes in the cells of lung adenocarcinoma metastasis to the brain after preoperative (neoadjuvant) Gamma Knife radiosurgery.
Material and methods: A 63-year-old female patient with brain metastases of lung adenocarcinoma including large metastasis in the right frontal lobe. Neoadjuvant stereotactic radiosurgery was performed by Leksell Gamma Knife Icon. Histological and immunohistochemical studies were performed after microsurgical removal of the metastasis in the right frontal lobe. The analysis of scanned images was performed using the NDP.view2 program of the Image Viewing software (© Hamamatsu Photonics K.K.).
Results: The result of histological and immunohistochemical studies is TTF-I+, ROS- lung adenocarcinoma. The most significant changes were coagulation necrosis, vasculopathy, altered blood vessels with endothelial damage, affected cells with pyknotic nuclei, and islets of coagulation necrosis with cells of adenocarcinoma. Despite the descriptive characteristics of early post-radiation changes, apparently caused by radiosurgical exposure, the specific mechanism of post-radiation reactions occurring in malignant cells of cerebral metastases remains to be understood. It is necessary to include the series of cases, in particular, with subsequent analysis of ultramicroscopic findings obtained by electron microscopy.
90-98
Nuclear Medicine
Quantitative Brain SPECT/CT with 99mTc-Technetril for Visualization and Assessment of the Functional State of Pituitary Adenomas
Resumo
Purpose: We tried to adapt the methodology for quantifying the accumulation of 99mTc-technetril (99mTc-MIBI) in pituitary adenomas, present a pharmacokinetic model for calculating blood flow in the pituitary gland based on the accumulation of 99mTc-technetril and evaluate their relationship with the level of prolactin in the blood in some pathological conditions.
Material and methods: The tumor blood flow (TBF) was calculated using the standardized radiopharmaceutical absorption value (SUV) and the minute volume of the heart (MV) as TBF = SUV99mTc-technetril × (MV / BodyWeight) × 100, where 100 is the conversion coefficient for representing the result in generally accepted units of ml/min/100 cm3 of tissue. The value of SUV99mTc-technetril can be determined using modern digital tomographic gamma cameras automatically, using source calibration with graduated specific radioactivity, or using phantoms with known radioactivity, with the construction of a regression relationship local kBq activity/ml – scintillation count per voxel and determining the true accumulation of radiopharmacutical in the tissue tumors, in kBq/cm3 units of tissue.
SPECT/CT of the brain with 99mTc-technetril (185–240 MBq, Gemini 700 gamma cameras and GE Discovery NM/CT 670 Pro) was performed in 8 patients without pituitary pathology (4 men and women, 34–63 years old) – control group, 9 patients with pituitary microadenomas (5 women and 4 men, 32–51 years old), and 8 patients (5 women and 3 men, 32–56 years old) with pituitary macroadenomas. All patients in groups 2 and 3 had an increase in blood prolactin levels > 35 mg/l, and all of them then received therapy with bromocriptine 2.5 mg/day or higher.
Results: Visually, SPECT/CT showed nodular inclusion in pituitary micro- and macroadenomas. SUV significantly differed between the groups and amounted to 1.23 ± 0.25 (0.85–1.39) in the control group, respectively, with microadenomas 7,20 ± 1,17 (4,5–12,9) (p < 0.02 compared with the control), and with macroadenomas 12.54 ± 3.62 (3.9–4.85) (p < 0.005). The tissue blood flow was, respectively 9,2 ± 2,0 (6,9–14,2): 36,9 ± 7,3 (26,3–72,3) (p < 0.01): and 68.3 ±14.9 (21.0–78.2)(p < 0.002. SUV99mTc-technetril > 5.8 for pituitary nodule was found to be correlated with blood prolactin levels of over 200 mg/l (p = 0.045). A decrease in the SUV99mTc-technetril of the pituitary gland < 3.9 during therapy with bromocriptine 2.5 mg/day was combined with a decrease in blood prolactin levels below 150 mg/l (p = 0.0482).
Conclusion: SPECT/CT of the brain with 99mTc-technetril is an informative additional method of examining patients with pathology of the hypothalamic-pituitary system and allows determining the standardized amount of radiopharmaceutical absorption, as well as pituitary blood flow. It is advisable to use SPECT/CT of the brain with 99mTc-technetril for prospective monitoring of therapy of pituitary pathology, as an adjunct to MRI. A further study of the role of pituitary SPECT/CT with 99mTc-technetril in a wider population of endocrinological patients is needed for inclusion in the standard algorithm and clinical recommendations for patient examination.
99-107
Radiation Physics, Technique and Dosimetry
Application of the Monte-Carlo Method for Calibration of a Gamma-ray Scintillation Spectrometer
Resumo
Purpose: To develop a method for calibration of a gamma-ray scintillation spectrometer using the Monte Carlo method.
Material and methods: The subject of the study was a gamma-ray spectrometer designed to measure the energy distribution (spectrum) and determine the activity of gamma-emitting radionuclides. Experimental studies were carried out with a set of exemplary measures of special-purpose activity with radionuclides 241Am, 152Eu, 60Co and 137Cs uniformly deposited on an ion exchange resin. Calibration of the spectrometer was carried out using the MCC 3D program (Monte Carlo Calculations 3D), modeling of the hardware spectrum was performed using the MCA program (MultiChannel Analyzer).
Results: The comparison of experimental and simulated spectra was carried out in the following energy intervals: the interval corresponding to the total peak of total absorption (PTA) for gamma energy lines 1173.2 keV and 1332.5 keV for 60Co and PTA for gamma energy line 661.7 keV for 137Cs; intervals corresponding to Compton scattering in the angle range (30–60)°, (60–90)° and (90–180)° (for the 60Co, the average gamma radiation energy of 1252.9 keV was considered); the interval corresponding to multiple scattering with an energy above 100 keV. It was found that the largest deviation of the simulated spectrum from the experimental one is 12 % for the interval corresponding to multiple scattering, which indicates the possibility of spectrum identity. This assumption was verified for each energy interval using the Pearson consensus criterion. A maximum value of χ2 equal to 6.6 was obtained for the energy interval corresponding to Compton scattering in the angle range (60–90)°, which indicates the acceptability of the hypothesis of the identity of the experimental and simulated spectra. Validation of the proposed method showed that the discrepancy between the calculated and passport activity of the sample was no more than 13 %, which indicates the possibility of using the method for calibration of the gamma spectrometer. The dependences of the efficiency of registration in the PTA on the density of the counting sample are calculated using simulated hardware spectra of single activity.
Conclusion: The proposed method makes it possible to calibrate the spectrometer to calculate the specific activity in samples at various densities and energies using spectrometric equipment equipped with inorganic scintillation crystals.
108-116
Professional Education
On the Legal Regulation of the Specialties Radiology and Radiotherapy in the Russian Federation
Resumo
Purpose: To study the specifics of legal and regulatory framework governing the specialties of Radiology (nuclear medicine) and Radiotherapy in the Russian Federation with regard to defining their nomenclature and further regulation.
Material and methods: Radiology, commonly referred to as nuclear medicine, originated in the late 19th century after the discovery of radioactivity. It is now extensively utilized in both diagnostic procedures and therapeutic treatments. However, there is significant confusion surrounding the definition of fundamental terms and concepts related to this branch of medicine, necessitating additional clarifications. The authors analyzed literary sources and legislative bases dedicated to issues of terminological and normative uncertainty in the field of nuclear medicine (radiology) in Russia. Discussed are differences in definitions of key terms such as “nuclear medicine,” “radiopharmaceutical preparation,” “radionuclide therapy,” and “radionuclide diagnostics.” Additionally, the problem of a lack of clear standards and rules in the field of nuclear medicine is raised, leading to difficulties in regulating and financing medical services.
Results: Proposed measures for improving the situation include developing unified terminology and standards, introducing the position of chief external radiotherapist, creating professional standards for radiologists and radiotherapists, and involving professional communities in addressing this issue.
Conclusion: The conducted research underscores the importance of resolving existing problems in legal and regulatory frameworks and terminological discrepancies in the fields of radiology and nuclear medicine in Russia. Emphasis is placed on the necessity of unifying terminology and definitions, establishing clear professional standards for specialists, and developing guidelines for conducting radionuclide studies. These measures should contribute to enhancing the quality of medical care, increasing the efficiency of professionals’ work, and ensuring proper funding of medical services through the compulsory health insurance system. The article proposes solving the identified problem by developing and approving terminology in the specialties of Radiology and Radiotherapy and making amendments to regulatory documentation.
117-120
