W B Li1, A Belchior2, M Beuve3, Y Z Chen4, S Di Maria2, W Friedland5, B Gervais6, B Heide7, N Hocine8, A Ipatov9, A P Klapproth10, C Y Li11, J L Li4, G Multhoff12, F Poignant3, R Qiu4, H Rabus13, B Rudek14, J Schuemann15, S Stangl12, E Testa3, C Villagrasa8, W Z Xie4, Y B Zhang16. 1. Institute of Radiation Medicine, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany. Electronic address: wli@helmholtz-muenchen.de. 2. Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela LRS, Portugal. 3. Institut de Physique Nucléaire de Lyon, Université de Lyon, Université Claude Bernard Lyon 1, CNRS/IN2P3 UMR 5822, Villeurbanne, France. 4. Department of Engineering Physics, Tsinghua University, Beijing, China. 5. Institute of Radiation Medicine, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany. 6. Normandie University, ENSICAEN, UNICAEN, CEA, CNRS, CIMAP, UMR 6252, BP 5133, F-14070 Caen Cedex 05, France. 7. Karlsruhe Institute of Technology, Karlsruhe, Germany. 8. Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-Aux-Roses, France. 9. Alferov Federal State Budgetary Institution of Higher Education and Science Saint Petersburg National Research Academic University of the Russian Academy of Sciences, St. Petersburg, Russia. 10. Institute of Radiation Medicine, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany; TranslaTUM, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. 11. Department of Engineering Physics, Tsinghua University, Beijing, China; Nuctech Company Limited, Beijing, China. 12. TranslaTUM, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. 13. Physikalisch-Technische Bundesanstalt, Braunschweig, Germany. 14. Physikalisch-Technische Bundesanstalt, Braunschweig, Germany; Massachusetts General Hospital & Harvard Medical School, Department of Radiation Oncology, Boston, MA, USA. 15. Massachusetts General Hospital & Harvard Medical School, Department of Radiation Oncology, Boston, MA, USA. 16. Peking University Cancer Hospital, Beijing, China.
Abstract
PURPOSE: Targeted radiation therapy has seen an increased interest in the past decade. In vitro and in vivo experiments showed enhanced radiation doses due to gold nanoparticles (GNPs) to tumors in mice and demonstrated a high potential for clinical application. However, finding a functionalized molecular formulation for actively targeting GNPs in tumor cells is challenging. Furthermore, the enhanced energy deposition by secondary electrons around GNPs, particularly by short-ranged Auger electrons is difficult to measure. Computational models, such as Monte Carlo (MC) radiation transport codes, have been used to estimate the physical quantities and effects of GNPs. However, as these codes differ from one to another, the reliability of physical and dosimetric quantities needs to be established at cellular and molecular levels, so that the subsequent biological effects can be assessed quantitatively. METHODS: In this work, irradiation of single GNPs of 50 nm and 100 nm diameter by X-ray spectra generated by 50 and 100 peak kilovoltages was simulated for a defined geometry setup, by applying multiple MC codes in the EURADOS framework. RESULTS: The mean dose enhancement ratio of the first 10 nm-thick water shell around a 100 nm GNP ranges from 400 for 100 kVp X-rays to 600 for 50 kVp X-rays with large uncertainty factors up to 2.3. CONCLUSIONS: It is concluded that the absolute dose enhancement effects have large uncertainties and need an inter-code intercomparison for a high quality assurance; relative properties may be a better measure until more experimental data is available to constrain the models.
PURPOSE: Targeted radiation therapy has seen an increased interest in the past decade. In vitro and in vivo experiments showed enhanced radiation doses due to gold nanoparticles (GNPs) to tumors in mice and demonstrated a high potential for clinical application. However, finding a functionalized molecular formulation for actively targeting GNPs in tumor cells is challenging. Furthermore, the enhanced energy deposition by secondary electrons around GNPs, particularly by short-ranged Auger electrons is difficult to measure. Computational models, such as Monte Carlo (MC) radiation transport codes, have been used to estimate the physical quantities and effects of GNPs. However, as these codes differ from one to another, the reliability of physical and dosimetric quantities needs to be established at cellular and molecular levels, so that the subsequent biological effects can be assessed quantitatively. METHODS: In this work, irradiation of single GNPs of 50 nm and 100 nm diameter by X-ray spectra generated by 50 and 100 peak kilovoltages was simulated for a defined geometry setup, by applying multiple MC codes in the EURADOS framework. RESULTS: The mean dose enhancement ratio of the first 10 nm-thick water shell around a 100 nm GNP ranges from 400 for 100 kVp X-rays to 600 for 50 kVp X-rays with large uncertainty factors up to 2.3. CONCLUSIONS: It is concluded that the absolute dose enhancement effects have large uncertainties and need an inter-code intercomparison for a high quality assurance; relative properties may be a better measure until more experimental data is available to constrain the models.
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