Issues
Preliminary estimation of the radiobiological response to carbon ion irradiation in silico and in vivo
«Radiation and Risk», 2025, vol. 34, No. 3, pp.131-145
DOI: 10.21870/0131-3878-2025-34-3-131-145
Authors
Kizilova Ya.V. – Researcher. Contacts: 4 Korolyov str., Obninsk, Kaluga region, Russia, 249035. Tel.: +7(484) 399-32-97 #7391; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .Koryakin S.N. – Head of Dep., C. Sc., Biol.
Khozyasheva T.S. – Laborant
Kolesnikova T.V. – Laborant
Troshina M.V. – Researcher
Lychagin A.A. – Lead. Researcher, C. Sc., Phys.-Math.
Minaeva N.G. – Lead. Researcher, C. Sc., Biol.
Solovev A.N. – Head of Lab., C. Sc., Phys.-Math. A. Tsyb MRRC.
Pikalov V.A. – Head of Lab. NRC “Kurchatov Institute” – IHEP.
1 A. Tsyb MRRC, Obninsk
2 Obninsk Institute for National Research Nuclear University MEPhI, Obninsk
3 Peoples' Friendship University of Russia named after Patrice Lumumba, Moscow
4 Institute for High Energy Physics named by A.A. Loginov of National Research Centre “Kurchatov Institute”, Protvino
Abstract
This study addresses the radiobiological efficacy of carbon ion irradiation generated at the U-70 accelerator facility. Particular emphasis is placed on a comprehensive methodology that integrates computational (in silico) techniques based on the earlier developed software with in vivo experiments on laboratory animals with engrafted tumors. This dual approach refines the spatial-energy parameters of the ion beam, ensures accurate formation of the Bragg peak, and evaluates the contribution of secondary particles to the overall radiobiological impact. The aim of this study was to perform a comprehensive assessment of the relative biological effectiveness of the ion beam. The assessment was carried out using experimentally measured absorbed doses and direct observations of tumor growth dynamics following irradiation, in combination with specially developed mathematical and software tools for validating and predicting the radiation spectrum and linear energy transfer characteristics. The absorbed dose estimate during experimental studies performed using ionization chambers, placed inside the object positioning system. After the irradiation, which take place on the 12 days after the tumor implantation, during the follow up period the tumor growth dynamics was analyzed during 25 days. The findings revealed a high level of radiobiological response to carbon ion irradiation, primarily attributable to the increased linear energy transfer and extensive cluster damage to DNA. The experiments also underscored the necessity for stringent dosimetric control and careful consideration of individual biological variability when assessing therapeutic outcomes. Hence, the integration of modeling and in vivo experimentation provides deeper insights into the mechanisms by which heavy ions interact with biological systems, enhances predictive accuracy for treatment efficacy, and establishes a foundation for optimizing ion therapy protocols in oncology.
Key words
radiation, carbon ion therapy, rats, M-1 sarcoma, radiobiological response, radiation therapy, mathematical modeling, biological dose, dosimetry, absorbed dose, U-70, image processing, software.
References
1. Antipov Yu.M., Britvich G.I., Ivanov S.V., Kalinin V.I., Lebedev O.P., Lyudmirskii E.A., Maksimov A.V., Minchenko A.V., Soldatov A.P., Khitev G.V. Slow extraction of a carbon-nuclei beam from the U-70 syn-chrotron. Instrum. Exp. Tech., 2021, vol. 64, no. 3, pp. 343-351.
2. Antipov Yu.M., Britvich G.I., Ivanov S.V., Kostin M.Yu., Lebedev O.P., Lyudmirskii E.A., Maksimov A.V., Pikalov V.A., Soldatov A.P., Khitev G.V., Ul’yanenko S.E., Lychagin A.A., Isaeva E.V., Beketov E.E., Troshina M.V. Transversally-flat dose field formation and primary radiobiological exercises with the carbon beam extracted from the U-70 synchrotron. Instrum. Exp. Tech., 2015, vol. 58, no. 4, pp. 552-561.
3. Pikalov V.A., Antipov Yu.M. Experimental facility “Radiobiological Test Setup on Accelerator U-70” as Centers for Collective Use (CCU). Proceeding of 26th Russian Particle Accelerator Conference (RuPAC’18), October 1-5, 2018. Protvino, IHEP, 2018, pp. 253-255.
4. Koryakina E.V., Potetnya V.I., Troshina M.V., Efimova M.N., Baykuzina R.M., Koryakin S.N., Lychagin A.A., Pikalov V.A., Ulyanenko S.E. Comparison of biological efficiency of accelerated carbon ions and heavy recoils in Chinese hamster cells. Radiatsiya i risk – Radiation and Risk, 2019, vol. 28, no. 3, pp. 96-106. (In Russian).
5. Beketov E.E., Isaeva E.V., Troshina M.V., Lychagin A.A., Solov’ev A.N., Koryakin S.N., Ulyanenko S.E., Malakhov E.P., Ulyanenko L.N., Kostin M.Yu., Pikalov V.A., Antipov Yu.M., Soldatov A.P. Results of preliminary study on the evaluation of the biological effectiveness of carbon ion beam from U-70 accelerator. Radiatsionnaia biologiia. Radioekologiia – Radiation Biology. Radioecology, 2017, vol. 57, no. 5, pp. 462-470. (In Russian).
6. Alekseev A.G., Pikalov V.A., Kiryukhin O.V. The use of thermoluminescent detectors for dosimetry in a carbon ion beam. Meditsinskaya fizika – Medical Physics, 2018, vol. 77, no. 1, pp. 11-12. (In Russian).
7. Zaichkina S.I., Rozanova O.M., Smirnova E.N., Dyukina A.R., Belyakova T.A., Strel’nikova N.S., Sorokina S.S., Pikalov V.A. Assessment of the biological efficiency of 450 MeV/nucleon accelerated carbon ions in the U-70 accelerator according to the criterion of mouse survival. Biofizika – Biophysics, 2019, vol. 64, no. 6, pp. 1208-1215. (In Russian).
8. Azhgirey I.L., Bayshev I.S., Kurochkin I.A., Pikalov V.A., Sumaneev O.V., Lukanin V.S. Neutron monitors for high energy accelerators. Proceeding of 26th Russian Particle Accelerator Conference (RuPAC’18), Octo-ber 1-5, 2018. Protvino, IHEP, 2018, pp. 224-226.
9. Solovev A.N., Chernukha A.E., Troshina M.V., Lychagin A.A., Pikalov V.A., Kharlov V.I., Ulyanenko S.E. Design of passive beam modifiers in carbon ion beam at U-70 synchrotron facility for radiobiological studies. Meditsinskaya fizika – Medical Physics, 2016, vol. 72, no. 4. pp. 47-54. (In Russian).
10. Solovev A., Troshina M., Pikalov V., Saburov V., Chernukha A., Moiseev A., Koryakina E., Potetnya V., Koryakin S., Soldatov A., Kaprin A. In vitro modified microdosimetric kinetic model-based predictions for B14-150 cells survival in 450 MeV/u carbon ion beam with aluminum ridge filter for biologically optimized spread-out Bragg peak. Biomed. Phys. Eng. Express, 2022, vol. 8, no. 3, pp. 035030. DOI: 10.1088/2057-1976/ac414f.
11. Troshina M.V., Koryakina E.V., Potetnya V.I., Solovev A.N., Saburov V.O., Lychagin A.A., Ivanov S.A., Kaprin A.D., Koryakin S.N. Biological response of Chinese hamster B14-150 cells to sequential combined exposure to protons and 12C ions. Bull. Exp. Biol. Med., 2023, vol. 176, no. 1, pp. 38-41.
12. Matchuk O.N., Selivanova E.I., Yakimova A.O., Saburov V.O., Solovev A.N., Troshina M.V., Litun E.V., Koryakin S.N., Pikalov V.A., Abramova M.R., Ivanov S.A., Zamulaeva I.A. Effects of combined exposure to carbon ions and protons on the pool of MCF-7 breast cancer stem cells in vitro. Bull. Exp. Biol. Med., 2023, vol. 176, no. 1, pp. 82-86.
13. Solovev A.N., Kizilova Ya.V., Kazakov E.I., Koryakin S.N. Programming and computing suite for the thera-peutic absorbed dose in radiotherapy. Russian Technological Journal, 2025, vol. 13, no. 4, pp. 7-24. (In Russian).
