Vol 69, No 4 (2024)
Radiation Biology
Study of Radiosensitising Properties of Lithium Ascorbate under Neutron Irradiation in Tumour Growth Models
Abstract
Background: Radiosensitivity of tumour cells is a serious problem in the treatment of oncological diseases, which, along with the dama- ging effect of irradiation on healthy tissues, significantly limit the possibilities of radiation therapy; therefore, an important task of modern oncopharmacology is the search and study of new radiosensitizing compounds. The main objective of this study was to investigate the radiosensitising effect of lithium ascorbate in vitro and in vivo under neutron radiation exposure.
Material and methods: Evaluation of biological effect in vitro was performed on cell culture of tumour line HCT-116 (human colorectal cancer). To develop a model of tumour growth in vivo, SPF-nude immunodeficient mice (line Nu/j) were used. In vivo xenografts were formed by subcutaneous injection of cell suspension of HCT-116 cell line at a concentration of 2 million cells per 100 µl. The drug was administered to animals before irradiation by intraperitoneal injection in physiological solution at the rate of 2.4 mM/kg of animal weight. Neutron irradiation of cells was performed on cyclotron P-7M, by neutron flux with average energy of 7.5 MeV in the range of absorbed doses of 0.5‒1.5 Gy. Local irradiation of mice tumours was performed once at a dose of 1.5 Gy on a cyclotron with the same flux parameters. Cell viability was assessed by MTT test. Tumour growth parameters were assessed by measuring the sizes of xenografts and calculating the average volume, tumour doubling time and animal life span.
Results: Enhancement of cytotoxic effect with combined application of radiation exposure and lithium ascorbate in vitro and in vivo was shown. A dose-dependent decrease in cancer cell viability was found when lithium ascorbate was used at a concentration of 0.1‒0.3 mM in combination with neutron irradiation. It was shown that the average tumour volume decreased by more than 50 % in comparison with the control, the xenografts growth rate slowed down to 72 %, and the median life expectancy of experimental animals increased by 86 % when lithium ascorbate and neutron irradiation were combined. Mechanisms of radiosensitising effect by induction of oxidative stress were proposed.
Conclusion: The use of lithium ascorbate results in a more pronounced therapeutic effect of neutron radiation exposure in cellular and animal models of tumour growth.
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Enhancement of the Cytotoxic Effect of Proton Irradiation by Gold Nanoparticles
Abstract
Purpose: To evaluate the bioefficiency and biosafety of proton irradiation in combination with gold nanoparticles (AuNPs) on a model of a higher invertebrate animal Daphnia magna from the suborder crustaceans in in vivo experiments.
Materials and methods: The synthesis of AuNPs was carried out by a single-stage method of femtosecond laser ablation. A laboratory culture of Daphnia magna (D. magna) was used. Animals were cultured in a climatostat (model P2). Biological parameters (viability, fertility and cytotoxicity) were evaluated in two consecutive generations (F0) and (F1). Only animals of the parental generation (F0) were exposed to acute irradiation with a scanning proton beam (energy 150 MeV) on the Prometheus proton complex. Viability and fertility D. magna were evaluated in a 21-day experiment on a daily basis. A total of 10 to 60 individuals were analyzed in control and experimental groups. Cytotoxicity was analyzed by an MTT test modified for studies of the effect on invertebrates in in vivo experiments. From 11 to 97 samples were analyzed for cytotoxicity. There were 20 animals in each sample. The results are analyzed by methods of mathematical statistics adjusted for multiple comparisons.
Results: Irradiation at doses of 10 and 30 Gy caused a decrease in animal viability, which was increased in 1.35 times. Reproductive dysfunction was found in both irradiated and first-generation animals. The use of AuNPs did not cause oxidative stress in D. magna, but increased the cytotoxic effect of proton irradiation. AuNPs contributed to the cytotoxic effect.
Conclusions: Since the results obtained are consistent with the data published in the cited articles on vertebrates, it is possible to assume a universal mechanism of cytotoxic effect of proton irradiation in combination with AuNPs on both invertebrates and vertebrates, including humans, and the possibility of using AuNPs as radiosensitizers to enhance the effect of irradiation in binary proton therapy technologies.
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Increased Radioresistance of Human Non-Small Cell Lung Cancer Cells Surviving Cisplatin Exposure
Abstract
Purpose: To evaluate radioresistance of human non-small cell lung cancer (NSCLC) cells that survived and showed sustained growth after exposure to cisplatin.
Material and methods: The work used the NSCLC cell line A549, which was exposed to cisplatin at a concentration of 2.5 μg/ml four times to obtain a cell population that survives and produces stable growth after exposure to cisplatin, A549Pt. Cell irradiation was carried out on a RUB RUST-M1 X-ray biological installation (Russia) at a dose rate of 0.85 Gy/min. Cell death was assessed using flow cytometry. To analyze the effectiveness of DNA repair from double-strand breaks (DSBs), we used a quantitative assessment of the foci of DNA DSB marker proteins γH2AX and 53BP1.
Results: A549Pt NSCLC cells that survived and grew robustly after exposure to cisplatin exhibited reduced activation of apoptosis and produced less 53BP1 in response to additional cisplatin exposure compared to parental A549 cells. A549Pt also exhibit resistance to X-ray radiation, manifested in a decrease in the quantitative yield of foci of DNA DSB marker proteins γH2AX and 53BP1. The resistance of A549Pt cells to the effects of ionizing radiation, revealed in this work, can significantly reduce the effectiveness of neoadjuvant chemoradiation therapy for malignant neoplasms. Further research is needed to identify the detailed cellular and molecular mechanisms of the resistance of surviving cells to radiation therapy acquired during chemotherapy. In the future, this will increase the effectiveness of treatment of malignant neoplasms and avoid relapses.
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Radiation Safety
Radiological Survey of Schools and Kindergardens in Snezhinsk
Abstract
Purpose: Radiological survey in schools and kindergardens of Snezhinsk, Chelyabinsk region.
Material and methods: Total 209 public premises on the ground floor and basements were examined. Ambient dose equivalent power measurements were performed by DKG-02U ARBITER. SSNTDs were used to measure annual indoor radon concentrations during the warm and cold seasons.
Results: Indoor gamma dose rate varies within the range 0.10–0.21 μSv/h. Annual equilibrium equivalent concentration of radon (EECRn) varies over a wide range up to 590 Bq/m3, exceeding 100 Bq/m3 in 10 % of surveyed premises. Average annual values of equivalent equilibrium concentration are about 30 Bq/m3 and characterize the radon situation as generally acceptable. The difference in the values of the EECRn in brick buildings and buildings made of reinforced concrete panels has been revealed. The average annual EECRn values reach 590 Bq/m3 in brick buildings, and 360 Bq/m3 in buildings made of reinforced concrete panels, with average values of 32 and 18 Bq/m3, respectively. Sealing brick and reinforced concrete buildings by installing plastic double-glazed windows enhances these differences.
Conclusions: The survey revealed a critical group of buildings with enhanced indoor radon. Old brick buildings (1950‒1970) with unventilated basements and installed plastic double-glazed windows are characterized by the highest indoor radon concentration in public premises. These type of buildings require in-depth radon research and planning of radon protection measures if necessary.
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The Essence of Radiogenic Damages in the Lens: Threshold, Tissue Reactions (Deterministic Effects), but not Stochastic, Non-Threshold Effects
Abstract
The purpose is to analyze the arguments ‘for’ and ‘against’ the assumption that radiogenic disturbances in the lens, previously considered as tissue reactions with a threshold (deterministic effects), may be stochastic events characterized by the absence of a threshold. The importance of the nature of radiation cataractogenesis for radiation safety is associated with the conceptual difference in approaches to developing Radiation Safety Standards. For threshold effects, Radiation Safety Standards with dose limits not exceeding the threshold is sufficient for 100 % protection, while for stochastic events, protection is based on the concept of ‘socially admissible risk’, since the probability of an effect exists at any radiation dose.
An analysis of four arguments in favor of the non-threshold and stochastic nature of radiogenic disturbances in the lens demonstrated that some considerations may not be relevant to the problem (such as the lack of a dose rate effect, which may be explained by the lack of DNA repair and cellular renewal in the lens). An attempt to justify the absence of a threshold of less than one by the value of the upper confidence interval for the risks in the cohort of victims of the atomic bombings is untenable based on the canons of statistics and epidemiology. Data on the effects of low-dose low-LET radiation (up to 0.1 Gy) on lens abnormalities are lacking for most study populations, and for those that have been reported (medical radiologists, industrial radiographers, and patients undergoing computed tomography), the results are inconsistent, non-system, and can be explained, among other things, by non-radiation factors. The last argument ‒ the molecular cellular prerequisites for the stochastic hypothesis (the presence of only a hypothetical biological mechanism) does not have direct evidentiary force in the field of epidemiology.
At the same time, there are strong arguments for the deterministic nature of radiogenic disorders in the lens. The main effect is the influence of the radiation dose on the severity of the pathology, which is typical only for tissue reactions. Experimental, epidemiological and environmental examples of dose dependencies for radiogenic disorders in the lens are presented, which cover almost all irradiated groups and conditions: effects on animals and people; radiation of different quality ‒ both low and high LET; for professional contingents, patients and residents of radioactively contaminated areas. Another argument is the long-term identification of threshold doses, both in laboratory and in epidemiological studies (from 2011–2012 to the present, the threshold is a dose of 0.5 Gy according to the ICRP and UNSCEAR). Based on these ICRP regulations, acceptable standards for lens irradiation were formed for professionals and the public.
The presented analytical study summarizes the discussion about the nature of radiogenic disorders in the lens: according to the totality of various correct data, these are threshold, tissue reactions (deterministic effects).
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Radiation Medicine
Studying the State of the Autonomic Nervous System and Hemodynamics in the Liquidators of the Accident at the Chernobyl NPP
Abstract
Purpose: Comparative analysis of changes in the state of the autonomic nervous system and hemodynamics in liquidators of the consequences of the Chernobyl accident and individuals in the comparison group exposed to low doses of ionizing radiation.
Material and methods: The study was carried out for 141 liquidators of the consequences of the Chernobyl accident and 84 male comparison group people aged from 30 to 50 years (41.24 ± 0.41) and (40.95 ± 0.54), respectively. Only liquidators could be exposed to ionizing effects. All of them, the dose of ionizing radiation did not exceed 0.5 Gy. All individuals underwent a clinical, neurological and electrophysiological examination in A.I. Burnazyan Federal Medical Biophysical Center. The main attention was paid to studying the state of the autonomic nervous system and hemodynamics in participants in the liquidation of the consequences of the Chernobyl accident.
Results: Clinical examination made it possible to diagnose neurological disorders in both groups in the form of: vegetative-vascular dystonia, neurocirculatory dystonia, dyscirculatory encephalopathy of various etiologies ‒ with a statistically significant predominance of their quantity and quality among liquidators. The changes observed in liquidators are functional and nonspecific.
Conclusions: In the group of liquidators, a significant increase in the number and severity of the considered neurological disorders was revealed. Comparison of the examined groups according to the state of central hemodynamics showed the absence of a statistically significant connection between the state of cerebral blood flow and low-dose irradiation. At the same time, a connection was established between the state of cerebral hemodynamics and systemic autonomic tone and the age of the examined individuals. The combination of permanent and paroxysmal autonomic disorders, psychosomatic disorders can be considered as a manifestation of hypothalamic dysfunction that has developed against the background of vascular disorders in the brain that have arisen with age.
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Phenomenology and Number of Neurological Manifestations in Liquidators of The Consequences of the Accident at the Chernobyl NPP with Low Doses of Ionizing Radiation and Observation Period
Abstract
Purpose: To analyze our own data on the dependence of neurological manifestations in liquidators of the Chernobyl accident on the dose within low values and observation time after irradiation.
Material and methods: The study was conducted with the participation of 141 liquidators of the consequences of a nuclear power plant accident. The analysis used clinical data on the nosology of neurological manifestations, which are presented in comparison with low radiation doses (31±6 and 190±22 mSv) and observation time after the accident (1986‒1988). The results are statistically substantiated.
Results: It was shown that there is no direct relationship between the incidence of neurological disorders and the dose of ionizing radiation within low values. On the contrary, a statistically significant predominance of their number was noted at lower doses – 31±6, relative to 190±22 mSv. The main phenomenology was reduced to neurocirculatory dystonia. The prevalence of vegetative-vascular dystonia and encephalopathy was almost the same during different periods of operation at the Chernobyl NPP and was always statistically significantly lower than the neurocirculatory dystonia. These data were correlated with the type of EEG activity.
Conclusion: The effects of low doses of ionizing radiation (31±6 and 190±22 mSv) during various periods of observation (1986‒1988) were characterized by a quantitative predominance of nosological forms in the form of neurocirculatory dystonia. Statistically significant, in a greater percentage of cases they were noted at lower doses (35.7 %, relatively, 18.7 % at higher doses). Analysis of observation periods of the effects of low doses confirms these data and represents the likelihood of their intensification in long-term observation periods: 1986 – 24.4 %, 1988 – 35.7 %, whereas at higher doses these changes were noted only in 1986 – 18.7 %.
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Digital Twin as a Tool of Participatory Medicine for Workers of Nuclear Facility
Abstract
Introduction.
Рarticipatory medicine.
Health, norm.
Pre-shift medical examination of workers of nuclear facility as a source of significant individual health indicators.
Technological infrastructure for data collection.
The digital twin as a tool of participatory.
Protection of personal medical data.
Conclusion.
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Radiation Diagnostics
Assessment of Midbrain Structure Visualization with Modified 3 Tesla MRI Protocols for Enhanced Parkinson's Disease Diagnosis
Abstract
Purpose: To assess the outcomes and implications of modifying SWAN protocol parameters on a 3 Tesla MRI for midbrain structure imaging in patients to detect signs of Parkinson’s disease.
Material and methods: The study was conducted on 22 patients of both genders, ranging in age from 30 to 77 years. Protocols for the standard MRI brain examination and its two variations in the SWAN program, which involved reducing the slice thickness, were analyzed. Key parameters for the visualization of midbrain structures were identified, and subsequently evaluated by expert radiologists.
Results: Parameters within the SWAN protocol for MRI scanning were identified, the modification of which enhances the clarity of nigrosome-1 visualization. It was established that thin-slice modifications of the brain scanning protocols (slice thicknesses of 1.2 and 2 mm) reveal early, diagnostically significant features of nigrosome-1 for Parkinson’s disease 3.4 to 4.1 times more frequently than the standard survey protocol with a slice thickness of 4 mm.
Conclusion: The significance of selecting appropriate MRI protocol parameters for studying midbrain structures to enhance the visualization effectiveness of nigrosome-1 has been confirmed. Employing the SWAN sequence on a 3 Tesla MRI scanner with a slice thickness of 2 mm or less in a neurological department setting during routine Parkinson’s disease examinations achieves superior imaging results compared to conventional survey MRI protocols with a 4 mm slice thickness. This approach demonstrates high inter-rater reliability and aligns with European recommendations for neuroimaging.
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CT and MRI in the Diagnostics of Intrahepatic Portocaval Shunt. Review of Literature and Case Reports
Abstract
Purpose: To describe two cases of diagnostic of intrahepatic portacaval shunt based on the computed (CT) and magnetic resonance tomography (MRI). Provide a brief review of the literature on this pathology.
Material and methods: Two case reports of patients with intrahepatic portacaval shunts which were diagnosed by CT and MRI with contrast enhancement.
Results and discussion: A peculiarity of the presented case reports was that in both cases the patients had oncopathology and were examined for the purpose of staging the disease. Due to the risk of cancer when analyzing CT and MRI images, focal changes in the liver can be mistakenly interpreted as metastases. In various situations, the attending physician may choose tactics for further observation, or decide to verify the identified changes in the liver. In the latter case, minimally invasive intervention can damage the shunt wall and cause bleeding. To avoid any complications, the radiologist have to identify and interpret vascular abnormalities in the liver confidently and unambiguously. The two presented case reports demonstrated typical signs of an intrahepatic porthocaval shunt, both according to CT and MRI. These include the connection of the lesion with the main vessels with similar dynamics of contrast enhancement, and the absence of signs of diffusion restriction.
Conclusion: The presented semiotics of the intrahepatic portacaval shunt according to CT and MRI data allows to diagnose it confidently and thus avoid the need for repeated studies or surgical intervention.
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Radiation Therapy
Results of Treatment of Patients with Stage I-II Breast Cancer after Subcutaneous/Skin-Preserving Mastectomies with Reconstruction with/without Radiation Therapy
Abstract
Purpos: To study the oncological results and features of complications in patients with breast cancer in stages I‒II after subcutaneous/skin-preserving mastectomies with reconstruction with/without radiation therapy. Material and methods: From 2013 to 2022, 984 breast cancer patients underwent 1020 subcutaneous/skin-preserving mastectomies with simultaneous one- or two-stage reconstruction at the Herzen Moscow Medical Research Institute. Subcutaneous mastectomy with reconstruction was performed in 617 (60.5 %), skin-preserving mastectomy in 403 (39.5 %) cases. Reconstruction with the patient’s own tissues was performed in 5.7 %, expanders/implants in 94.3 % of patients. Results: The recurrence rate of breast cancer was 41 (4.2±0.6 %), the frequency of distant metastases was diagnosed in 53 (5.4±0.7 %) in the studied group of patients. Complications were diagnosed in 241 (24.5 %) patients. Recurrence in the group with radiation therapy was 2.6±0.6 (OR 0.98, CI 1.52‒3.48, 95 %), without radiation therapy 5.9 % (OR 2.13, CI 0.92‒5.18, 95 %) regardless of the stage of breast cancer (criterion T > 2, p ˂ 0,05). Capsular contracture (CC) of the III‒IV degree was diagnosed in 9.4 % of the analyzed group of patients. Capsular contracture of the III‒IV degree worsens the aesthetic result of breast reconstruction, as well as reduces the quality of life of patients. With simultaneous two–stage reconstruction, the risk of developing CC was 4.2 % (after LT 4.7 %, without LT 3.6 %), with one-stage reconstruction, the risk of developing CC 11.2 % (after LT 15.8 %, without LT 4 %). In the study group of patients, the effect of LT on the risk of CC was 12.6 %, without LT 3.7 % (p < 0.05), the difference is statistically significant. In our study, the recurrence of breast cancer at the edge of R1 was 6.8±2.5 %, at R0 – 3±0.6 % (p > 0.05). When analyzing the age and risk of recurrence, we did not identify an age dependence, before 40 years the probability of recurrence was 4.3±1 %, after 40 years – 3.3±0.7 % (criterion T = 0.44, p > 0.05). A statistically significant difference in our study was revealed, except for radiation therapy, during NAPHT, thus, in the group with NAPHT, the recurrence was 2.4± 0.8 %, without NAPHT – 4.6±0.7 % (criterion T = 2.16, p ˂ 0.05). When performing a simultaneous two-stage reconstruction of a patient with the inclusion of radiation therapy (LT), the risk of skin protrusion was 18 %, without radiation therapy – 8.3 %. Capsular contracture (CC) of the III‒IV degree was diagnosed in 9.4 % of the analyzed group of patients. Capsular contracture of the III‒IV degree worsens the aesthetic result of breast reconstruction, as well as reduces the quality of life of patients. With simultaneous two–stage reconstruction, the risk of developing CC was 4.2 % (after LT 4.7 %, without LT 3.6 %), with one-stage reconstruction, the risk of developing CC 11.2 % (after LT 15.8 %, without LT 4 %). In the study group of patients, the effect of LT on the risk of CC was 12.6 %, without LT 3.7 % (p < 0.05), the difference is statistically significant.
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Nuclear Medicine
SPECT/CT with a New Radiopharmaceutical "99mtc, Octreotide" in Diagnosis and Evaluation of the Effectiveness of Treatment of Neuroendocrine Tumor of the Lung (Clinical Case)
Abstract
Purpose: to demonstrate the possibilities of using SPECT/CT with the new radiopharmaceutical “99mTс, Octreotide” in the diagnosis, assessment of the extent of the process and monitoring of the effectiveness of treatment of neuroendocrine lung tumors.
Material and methods: the presented clinical case examines the medical history of a patient with verified neuroendocrine cancer of the right lung with extensive local spread and the presence of distant lymph node metastases (retroperitoneal lymph nodes) and hematogenous dissemination to bones (ribs and vertebrae). During the initial diagnosis and at the stages of chemotherapy treatment, along with traditional methods of instrumental and laboratory examination, the patient underwent “99mTc, Octreotide” SPECT/CT. The results of the study were assessed visually and using the SUV (standardized accumulation level). When interpreting the results of “99mTc, Octreotide” SPECT/CT with special attention was paid to the dynamics of the SUV indicator at control points for assessing the effectiveness of chemotherapy treatment.
Results: The results obtained demonstrated the possibility of effective use of “99mTc, Octreotide” SPECT/CT at the stage of primary diagnosis of a neuroendocrine tumor. The data obtained not only confirmed the presence of a malignant tumor of a neuroendocrine nature in the patient, but also made it possible to correctly stage the tumor process, since additional pathological foci were identified in distant lymph nodes and bones. In addition, the use of “99mTc, Octreotide” SPECT/CT during control examinations at the stages of chemotherapy treatment of a patient made it possible to supplement the significance of diagnostic information obtained using traditional research methods and to more reliably assess the effectiveness of the therapy. Already at the first control examination, pronounced positive dynamics were observed after 3 courses of chemotherapy in the form of a decrease in the number of foci of pathological accumulation of “99mTc, Octreotide” and a decrease in the intensity of its inclusion in the remaining areas of the tumor lesion. Also, during further examinations at control points, the opposite – negative dynamics was noted in the form of the appearance of new foci of pathological accumulation of “99mTc, Octreotide”.
Conclusion: The presented experience in the clinical use of “99mTc, Octreotide” SPECT/CT demonstrated the effectiveness and ease of use of this method in patients with neuroendocrine tumors. In addition, the results obtained today make it possible to successfully use the new domestic radiopharmaceutical for the diagnosis of neuroendocrine tumors.
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The Importance of the SPECT/СT in the Diagnosis of Asymptomatic Myocardial Ischemia for a Specific Patient
Abstract
Purpose: To demonstrate a clinical observation in which the diagnosis of ischemic heart disease with vasospastic coronary microvascular dysfunction was established mainly using 99mTc-MIBI SPECT/CT.
Material and methods: In patient G.D.S., 39 years old by profession of an electric locomotive driver, who did not present any health complaints, oblique ST segment depression was registered during Holter monitoring on ECG. The following methods were used to establish the diagnosis: echocardiography, X-ray computed tomography (CT) to assess coronary artery calcinosis, single-photon emission computed tomography (SPECT) with 99mTc-technetril to assess myocardial perfusion and contractile function on hybrid SPECT/CT system SymbiaT16 (Siemens), coronary angiography (CAG).
Results: Only at examination on hybrid tomograph at rest and during physical activity (bicycle ergometer 125 W ‒ 5 minutes), sequentially applying in one diagnostic procedure two studies (CT and SPECT with 99mTc-MIBI) 26 study parameters were obtained (at CT ‒ 4 parameters evaluating coronary artery calcinosis, at SPECT ‒ 11 parameters of perfusion and 11 parameters of myocardial function). The absence of coronary artery calcinosis was revealed (which was confirmed by CAG), and the study at rest and during exercise revealed a decrease in perfusion (hence myocardial blood flow) in the apical-lateral (16-th segment); apex (17), apical-anterior (13), anterior-medial (7), anterolateral middle (12); irreversibility of perfusion defect, total and ischemic perfusion deficit.
Conclusion: A clinical observation is demonstrated in which, only the use of hybrid SPECT/CT system allowed to establish the absence of coronary artery calcinosis and the decrease of perfusion (hence myocardial blood flow), irreversibility of perfusion defect, total and ischemic perfusion deficit (all listed indices had penultimate moderately pronounced degree).
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