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O.7.2 RADIOBIOLOGICAL EFFECTS OF PROTONS OR GAMMA RAYS AND UVB RADIATION ON HUMAN CELLS

Georgakilas, Alexandros

Abstract

Contact person : Alexandros Georgakilas, National Technical University of Athens (NTUA), Athens, Greece EMAIL: [email protected] Project: 21GRD02 BIOSPHERE The project (21GRD02 BIOSPHERE) has received funding from the European Partnership on Metrology, co-financed by the European Union's Horizon Europe Research and Innovation Programme and by the Participating States. Funded by the European Union.

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Abstracts / Physica Medica 127S1 (2024) S1–S82 S19 Quadratic Discriminant Analysis (QDA), Logistic Regression (LR), Random Forest (RF), Support Vector Machine (SVM), Support Vector Regressor (SVR), Linear Regression (LinR), 2nd-degree Polynomial Regression (PolR), kNN regression (kNNR), and XGBoost (XGB). Results: The results revealed that the SVM algorithm achieved the highest accuracy for the 2-class classification (Task 5, 97.1%), whereas the LDA algorithm outperformed others in the 3-class classification (Task 7, 99.7%). Regarding the regression scheme, the SVR algorithm exhibited the lowest mean absolute error (Task 7, 3.6). Conclusion: The utilization of machine learning algorithms significantly enhances the objective assessment of surgical skills and advances training methodologies within virtual reality simulators. Physica Medica 127S1 (2024) 104565 https://doi.org/10.1016/j.ejmp.2024.104565 Biophysics and Radiobiology (BRB) O.7.1 STANDARD VS FLASH PROTON RADIATION: AN ULTRASTRUCTURAL STUDY OF TISSUES USING TRANSMISSION ELECTRON MICROSCOPY-TEM I. Tremi1,2, A. Velalopoulou3, I. I. Verginiadis3, I. Dokic4,5,6, F. E. Fyrios2, S. Havaki1, V. G. Gorgoulis1,7,8,9,10, C. Koumenis3, A. G. Georgakilas2 1Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece, 2Department of Physics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Athens, Greece, 3Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA, 4Clinical Cooperation Unit Translational Radiation Oncology, German Cancer Consortium (DKTK) Core-Center Heidelberg, National Center for Tumor Diseases (NCT), Heidelberg University Hospital (UKHD) and German Cancer Research Center (DKFZ), Heidelberg, Germany, 5Division of Molecular and Translational Radiation Oncology, Heidelberg Faculty of Medicine (MFHD) and Heidelberg University Hospital (UKHD), Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany, 6Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Oncology (NCRO), Heidelberg University Hospital and German Cancer Research Center (DKFZ), Heidelberg, Germany, 7Biomedical Research Foundation, Academy of Athens, Athens, Greece, 8Ninewells Hospital and Medical School, University of Dundee, Dundee, UK, 9Faculty Institute for Cancer Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK, 10Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK Background: Radiotherapy (RT) is effective in cancer treatment but is also associated with adverse toxic effects in the surrounding normal tissues. FLASH RT, an ultra-high dose rate radiation, has shown promise in maintaining local tumor control with reduced normal tissue toxicities compared to conventional RT (standard dose rate). Although the underlying mechanisms behind the FLASH sparing effect are still not fully understood, the most plausible theory at this time is that reactive oxygen species generation and oxygen tension play a significant role. Given that the radiation impact in cells or tissues at an ultrastructural level is not yet well investigated, the aim of our study was to evaluate potential differences in tissue damage between standard RT (SRT) and FLASH RT (FRT), using Transmission Electron Microscopy (TEM). Materials and Methods: The whole abdomen of C57Bl/6 mice was irradiated with either 12 Gy of proton SRT or proton FRT. Jejunum segments were isolated at 0.5h, 4h and 18h post-irradiation and then fixed until further processing. Additionally, brain cortical tissues were irradiated with 10Gy of 4He SRT or 4He FRT and were isolated and fixed 7 days following irradiation. TEM processing of tissues included dehydration, infiltration and embedding in epoxy resin. Thin epoxy sections (~80nm thickness) were mounted on copper grids, and imaged using JEOL JEM 2100plus TEM, operated at 80 kV equipped with CMOS Camera Gatan OneView. Results: All irradiated tissues exhibited mitochondrial damaged, the intensity of which varied across time points and treatment modalities. SRT-treated tissues exhibited dilated rough endoplasmic reticulum, damaged intercellular contacts. In contrast, tissues treated with FRT showed an increase in autophagic vacuoles. Conclusion: While radiation may have similar effects on tissues, ultrastructural difference between the SRT and FRT are also present. Physica Medica 127S1 (2024) 104566 https://doi.org/10.1016/j.ejmp.2024.104566 O.7.2 RADIOBIOLOGICAL EFFECTS OF PROTONS OR GAMMA RAYS AND UVB RADIATION ON HUMAN CELLS A. Gkikoudi1,2, S. N. Vasilopoulos1,3, C. Beinke4, A. Al-Qaaod5, U. Giesen5, F. Krasniqi5, G. I. Terzoudi2, A. G. Georgakilas1 1DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens, Athens, Greece, 2Laboratory of Health Physics, Radiobiology & Cytogenetics, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Centre for Scientific Research “Demokritos”, Athens, Greece, 3Department of Science and Mathematics, Deree-The American College of Greece, Athens, Greece, 4Bundeswehr Institute of Radiobiology, University of Ulm, Munich, Germany, 5Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Germany Background: Radiation from cosmic and solar sources constitutes a significant environmental factor influencing human health on Earth. Although studies have traditionally examined the biological effects of the different radiation types individually, emerging research suggests that combined exposure may induce synergistic effects, altering cellular responses in ways yet to be fully understood. The purpose of this research work is to study the synergistic effects of ionizing and UVB radiations on human cells. Materials and Methods: The impact of the combined radiation exposure on normal primary human lymphocytes and human cell lines (skin fibroblasts, keratinocytes) was estimated by assessing cell viability, DNA Damage and genomic instability. Cells were exposed to J rays, or protons, followed by UVB exposure. MTT assay was applied to estimate cell viability, DNA Damage Response and Repair proteins JH2AX and 53BP1 were studied using immunofluorescence, and chromosomal aberrations, such as dicentric chromosomes, were scored in metaphase spreads. These approaches were also applied in human osteosarcoma cells, in order to examine the potential of UVB as a radiosensitizer. Results: Immunofluorescence results have shown elevated residual DNA Damage in co-exposed samples compared to those exposed to ionizing radiation only, in both healthy and cancer cell lines, with the effect being more intense in cancer cells. Formation of dicentric chromosomes in human peripheral blood lymphocytes revealed increased genomic instability in co-exposed samples compared to proton irradiation alone. Conclusion: The utilization of these experimental approaches aims to comprehensively investigate the effects of the combination of S20 Abstracts / Physica Medica 127S1 (2024) S1–S82 solar UV and cosmic ionizing radiation to evaluate their effects on healthy human cells, as well as on cancer cells. Physica Medica 127S1 (2024) 104567 https://doi.org/10.1016/j.ejmp.2024.104567 O.7.3 RADPHYSBIO: A RADIOBIOLOGICAL DATABASE FOR THE PREDICTION OF CELL SURVIVAL UPON EXPOSURE TO IONIZING RADIATION V. Zanni1, D. Papakonstantinou2, S. A. Kalospyros1, D. Karaoulanis3, G. M. Biz1, A. Adamopoulos4, A. Pavlopoulou5,6, A. G. Georgakilas1 1DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens, Athens, Greece, 2Department of Life Sciences, University ParisSaclay, Saint-Aubin, Paris, France, 3School of Electrical and Computer Engineering, National Technical University of Athens, Athens, Greece, 4Department of Medicine, Medical Physics Laboratory, Democritus University of Thrace, Alexandroupolis, Greece, 5Izmir Biomedicine and Genome Center (IBG), Balcova, Izmir, Turkey, 6Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Balcova, Izmir, Turkey Background: In the field of radiobiology, there are few databases that provide information on biology of the irradiated cells. Such databases can serve as valuable resources, since they provide access to a large volume of data that contribute to our understanding of radiation’s biological effects. However, they usually consider only one type of radiation, including few parameters in terms of biological response. Herein, we developed a computational biophysical model, which is able to predict the response of human cells (complex DNA lesions and cell survival) after exposure to different types of ionizing radiation. Our scope was the development of a radiobiological open-access database, ‘RadPhysBio’, which includes several physical and biological parameters, as well as the development of a machine learning (ML) biophysical model/prediction tool. Materials and Methods: Concerning the database, we mined experimental ionizing radiation data of human cells treated with X-rays, J-rays, carbon ions, protons and D-particles, by manually searching literature in PubMed from 1980 until 2023. Through WebPlotDigitizer software we calculated the cell survival D and E coefficients of the linear quadratic model, as well as the initial values of the double-strand breaks in DNA, while in order to complete any missing data, we produced complex DNA damage results through the fast Monte Carlo code MCDS. Results: The calculated D/E values are in a good agreement with those reported in literature, where D shows a relatively good correlation with linear energy transfer. In general, a positive correlation between DSBs and LET was observed as far as the experimental values are concerned. Furthermore, the ML model showed a good performance for D, while it underscored LET as the most important feature for its prediction. Conclusion: In conclusion, this work provides a robust tool for researchers and clinicians to better understand and predict radiation’s biological effects, which could be crucial for improving cancer treatment strategies. Physica Medica 127S1 (2024) 104568 https://doi.org/10.1016/j.ejmp.2024.104568 Biomedical engineering (BME) O.8.1 INVESTIGATION OF NOVEL X-RAY DETECTOR SETUPS IN CONE BEAM COMPUTED TOMOGRAPHY E. Karali1, C. Michail1, G. Fountos1, N. Kalyvas1, I. Valais1 1Department of Biomedical Engineering, Radiation Physics, Materials Technology and Biomedical Imaging Laboratory, University of West Attica, Athens, Greece Background: Cone beam computed tomography (CBCT) emerges as an alternative to classical mammography and even to tomosynthesis. CBCT offers 3D breast representation, without any breast compression, at adequate dose levels. CBCT can provide images with high sensitivity and specificity allowing a more accurate evaluation even in dense breast, where mammography and tomosynthesis may lead to false diagnosis. Materials and Methods: The purpose of this study is to present and evaluate novel detector schemes of a micro-CBCT system. Moreover, their imaging performance in the case of breast tissue examination is assessed. So, an X-ray cone beam micro-CT system, was simulated. The energy spectrum of the source ranges from 10 to 40 keV. The object under examination was placed on a 360° rotating table. Different detector materials were simulated and investigated: BGO, LSO, LYSO, LuAG, LaCl3 and CZT. Each energy converter was of the same size. Spatial resolution was investigated with simulated data of a bone tissue capillary. Further, a breast phantom, was simulated in order to evaluated image quality. The image quality comparison criteria were derived from contrast-to noise ratios (CNRs) of specific ROIs (regions-of-interest). System simulation was based on GATE software. Images were reconstructed with FBP and OSEM. The evaluation was performed in conjunction to the standard CsI:Tl detector scheme. All schemes were simulated with the same frond-end electronic configuration. Results: Spatial Resolution that can be achieved by all the aforementioned X-ray detection schemes depends only on the reconstruction algorithm. However, image quality showed a dependence on detector material. LYSO:Ce, LaBr3:Ce and LuAG:Ce presented adequate CNRs for materials of different density, while CZT performed well in low density spine bone tissue. Conclusion: The aforementioned examined materials with increased CNRs could be an efficient alternative for the case of dense breasts in a future CBCT system. Physica Medica 127S1 (2024) 104569 https://doi.org/10.1016/j.ejmp.2024.104569 O.8.2 CUSTOM-MADE PLA FILAMENT DOPED WITH THERMOLUMINESCENCE POWDER, FOR CONSTRUCTING 3D PRINTED RADIATION DETECTORS: PRELIMINARY RESULTS G. Giakoumettis1, N. Okkalidis2, F. Okkalidis2, C. Chatsigeorgiou2, H. Yordanov3, M. Gelev4, A. Siountas1, E. Papanastasiou1 1Medical Physics & Digital Innovation Laboratory, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece, 2Morphé, Thessaloniki, Greece, 3Faculty of Physics, Sofia University St. Kliment Ohridski, Sofia, Bulgaria, 4Protecta Labs, Sofia, Bulgaria Background: Thermoluminescent dosimeters (TLDs) are used to measure radiation dose and monitor the radiation exposure of