Abstract

The recently observed FLASH effect describes the observation of normal tissue protection by ultra-high dose rates (UHDR), or dose delivery in a fraction of a second, at similar tumor-killing efficacy of conventional dose delivery and promises great benefits for radiotherapy patients. Dedicated studies are now necessary to define a robust set of dose application parameters for FLASH radiotherapy and to identify underlying mechanisms. These studies require particle accelerators with variable temporal dose application characteristics for numerous radiation qualities, equipped for preclinical radiobiological research. Here we present the dresden platform, a research hub for ultra-high dose rate radiobiology. By uniting clinical and research accelerators with radiobiology infrastructure and know-how, the dresden platform offers a unique environment for studying the FLASH effect. We introduce its experimental capabilities and demonstrate the platform’s suitability for systematic investigation of FLASH by presenting results from a concerted in vivo radiobiology study with zebrafish embryos. The comparative pre-clinical study was conducted across one electron and two proton accelerator facilities, including an advanced laser-driven proton source applied for FLASH-relevant in vivo irradiations for the first time. The data show a protective effect of UHDR irradiation up to 105Gy/s and suggests consistency of the protective effect even at escalated dose rates of 109Gy/s. With the first clinical FLASH studies underway, research facilities like the dresden platform, addressing the open questions surrounding FLASH, are essential to accelerate FLASH’s translation into clinical practice.

Details

Title
The dresden platform is a research hub for ultra-high dose rate radiobiology
Author
Metzkes-Ng, Josefine 1 ; Brack, Florian-Emanuel 1 ; Kroll, Florian 1 ; Bernert, Constantin 2 ; Bock, Stefan 1 ; Bodenstein, Elisabeth 3 ; Brand, Michael 4 ; Cowan, Thomas E. 2 ; Gebhardt, René 1 ; Hans, Stefan 4 ; Helbig, Uwe 1 ; Horst, Felix 3 ; Jansen, Jeannette 5 ; Kraft, Stephan D. 1 ; Krause, Mechthild 6 ; Leßmann, Elisabeth 1 ; Löck, Steffen 7 ; Pawelke, Jörg 3 ; Püschel, Thomas 1 ; Reimold, Marvin 1 ; Rehwald, Martin 1 ; Richter, Christian 8 ; Schlenvoigt, Hans-Peter 1 ; Schramm, Ulrich 2 ; Schürer, Michael 9 ; Seco, Joao 10 ; Szabó, Emília Rita 11 ; Umlandt, Marvin E. P. 2 ; Zeil, Karl 1 ; Ziegler, Tim 2 ; Beyreuther, Elke 3 

 Helmholtz-Zentrum Dresden–Rossendorf, Dresden, Germany (GRID:grid.40602.30) (ISNI:0000 0001 2158 0612) 
 Helmholtz-Zentrum Dresden–Rossendorf, Dresden, Germany (GRID:grid.40602.30) (ISNI:0000 0001 2158 0612); TUD Dresden University of Technology, Dresden, Germany (GRID:grid.4488.0) (ISNI:0000 0001 2111 7257) 
 Helmholtz-Zentrum Dresden–Rossendorf, Dresden, Germany (GRID:grid.40602.30) (ISNI:0000 0001 2158 0612); TUD Dresden University of Technology, Helmholtz-Zentrum Dresden–Rossendorf, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden, Germany (GRID:grid.40602.30) (ISNI:0000 0001 2158 0612) 
 Center for Regenerative Therapies (CRTD), TUD Dresden University of Technology, Dresden, Germany (GRID:grid.4488.0) (ISNI:0000 0001 2111 7257); Cluster of Excellence - Physics of Life, TUD Dresden University of Technology, Dresden, Germany (GRID:grid.517293.b) 
 German Cancer Research Center (DKFZ), Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584); Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662) 
 Helmholtz-Zentrum Dresden–Rossendorf, Dresden, Germany (GRID:grid.40602.30) (ISNI:0000 0001 2158 0612); TUD Dresden University of Technology, Helmholtz-Zentrum Dresden–Rossendorf, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden, Germany (GRID:grid.40602.30) (ISNI:0000 0001 2158 0612); TUD Dresden University of Technology, Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden, Germany (GRID:grid.412282.f) (ISNI:0000 0001 1091 2917); German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Dresden, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584); National Center for Tumor Diseases (NCT/UCC), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Medizinische Fakultät and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany (GRID:grid.40602.30) (ISNI:0000 0001 2158 0612) 
 TUD Dresden University of Technology, Helmholtz-Zentrum Dresden–Rossendorf, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden, Germany (GRID:grid.40602.30) (ISNI:0000 0001 2158 0612); TUD Dresden University of Technology, Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden, Germany (GRID:grid.412282.f) (ISNI:0000 0001 1091 2917); German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Dresden, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584) 
 Helmholtz-Zentrum Dresden–Rossendorf, Dresden, Germany (GRID:grid.40602.30) (ISNI:0000 0001 2158 0612); TUD Dresden University of Technology, Helmholtz-Zentrum Dresden–Rossendorf, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden, Germany (GRID:grid.40602.30) (ISNI:0000 0001 2158 0612); TUD Dresden University of Technology, Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden, Germany (GRID:grid.412282.f) (ISNI:0000 0001 1091 2917); German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Dresden, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584) 
 TUD Dresden University of Technology, Helmholtz-Zentrum Dresden–Rossendorf, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden, Germany (GRID:grid.40602.30) (ISNI:0000 0001 2158 0612); National Center for Tumor Diseases (NCT/UCC), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Medizinische Fakultät and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany (GRID:grid.40602.30) (ISNI:0000 0001 2158 0612) 
10  German Cancer Research Center (DKFZ), Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584); Ruprecht-Karls-University, Faculty of Physics and Astronomy, Heidelberg, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373) 
11  ELI ALPS, ELI-HU Non-Profit Ltd., Szeged, Hungary (GRID:grid.7700.0); University of Szeged, Department of Oncotherapy, Szeged, Hungary (GRID:grid.9008.1) (ISNI:0000 0001 1016 9625) 
Pages
20611
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2892810175
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.