Speaker
Description
Radiotherapy delivered at ultra-high dose-rates (UHDR,> 40 Gy/s) can preserve tumour-control efficacy while reducing normal-tissue toxicity, a phenomenon known as the FLASH effect. Despite intense research efforts, the underlying mechanisms remain poorly understood and the conditions required for the occurrence of the FLASH effect are still under debate. Recent studies suggest that not only the average dose rate, but also the temporal beam structure and pulse characteristics may play a crucial role in determining the biological response [1].
The origin of the FLASH effect may be linked to modifications of the ultrafast (physico-)chemical processes induced by ionizing radiation. However, investigating these processes experimentally is challenging due to a lack of radiation sources capable of delivering the extreme instantaneous dose rates needed to access this regime.
The European X-ray Free-Electron Laser (EuXFEL) provides unique irradiation conditions, enabling dose rates exceeding TGy/s and exploration of ultrafast (physico-)chemical processes inaccessible with conventional radiation sources. The unique pulse structure of the EuXFEL beam enables investigation of whether temporal irradiation patterns contribute to radiation-chemical responses relevant to the FLASH effect. In this work, we propose the development of an experimental platform for studying radiation chemistry as a function of absorbed dose, dose-rate, and beam structure. Key components include the implementation of validated fluorescence and chemical dosimetry, as well as the design of temperature-control and chemically inert sample cells compatible with EuXFEL operation and safety requirements.
Representative radiosensitizers and plasmid DNA will be investigated in solution using an unfocused XFEL beam providing homogeneous dose deposition. By systematically varying irradiation conditions, we aim to identify radiation-chemical pathways sensitive to dose, dose rate, and pulse structure, and to establish their potential relevance to the FLASH effect using absorption and fluorescence spectroscopies and spin traps. Among the investigated systems, plasmid DNA will be used to assess radiation-induced damage, while Nibrozetone (RRx-001) will be used to determine whether radiosensitizing properties are retained or modified under UHDR irradiation conditions.
The present work establishes the methodological and experimental framework for future XFEL irradiation studies. These experiments will provide insights into the early stages of radiation action under extreme irradiation conditions and contribute to a mechanistic understanding of the FLASH effect, ultimately supporting the development and clinical implementation of FLASH radiotherapy.
References
[1] Y. Yang and F.-F. Yin, "Understanding of FLASH radiotherapy through physical to biological interpretation," Radiation Medicine and Protection, vol. 6, no. 4 pp. 187-195,Aug. 2025. doi.org/10.1016/j.radmp.2025.07.002.
