Ultra-high dose-rate radiobiology
The advancement of radiotherapy relies on radiobiological research providing mechanistic understanding and validation of new ideas prior to patient treatment. Following the translational chain, new methods and techniques are firstly studied in cells, followed by animal models of increasing complexity and concluded in clinical trials. Our team is specialized in establishing experimental setups and preclinical models allowing radiobiological research at large research accelerators, laser driven beams and clinical machines as well.
The Dresden platform for ultra-high dose rate radiobiology
The Dresden platform for high dose-rate radiobiology comprises different accelerators used by the team for radiobiological research: the clinical electron Linacs of the University Hospital Radiation Therapy Department, the proton cyclotron of the University Proton Therapy Dresden, the ELBE electron research accelerator and the Draco laser driven electron and proton beams. Moreover, the platform also includes groups working on beam transport and dose delivery, beam monitoring and dosimetry, biological research infrastructure and biological models, altogether necessary requirements for meaningful radiobiological studies.
The Dresden Platform offers a unique environment for studying the FLASH effect, with an unprecedented range of electron and proton dose rates (up to 10^9 Gy/s). In close cooperation with the group of Laser-Radiooncology at Oncoray - National Center for Radiation Research in Oncology and the groups of Laser-driven Ion acceleration and Application-oriented laser-plasma accelerators at DRACO, the team contributes to FLASH radiotherapy research investigating beam interactions across physico-chemical and biological timescales. To enable the study of radiobiological effects of ultra-high dose rates, but also clincal dose delivery, the team develops and validates dedicated cell and animal models for tumor and normal tissue response.
The discovery of ultra-high dose rate radiation effects such as the FLASH-effectFavaudon have sparked intensive radiobiology research worldwide. Flash-RT promises the protection of normal tissue by high dose rate radiotherapy, while simultaneously not altering tumour control. The optimistic prospect of better cancer cure and improved quality of patient life give rise to manifold preclinical studies on the parameters and mechanisms of the Flash effect. Our team used the available accelerators of the Dresden platform to study the influence of physical and environmental parameters on the electron and proton Flash effect. For that purpose, the zebrafish embryo model, a small normal tissue vertebrate model, is applied allowing high-throughput normal tissue response studies. Up to know, the importance of beam parameters, like beam pulse structure, mean dose rate and linear energy transer, could be shown. The next steps involve more mechanistic investigations together with the group of Biomedical Physics in Radiation Oncology at DKFZ on biological and biochemical pathways aiming on the mechanism behind the Flash effect.
Deutsche Krebshilfe: "Dosisleistungsabhängige Änderung des Sauerstoffpartialdrucks während FLASH-Bestrahlung und deren Einfluss auf die strahlenbiologische Wirkung in Zebrafisch Embryonen", 2023-2026
Zebrafish Embryo Model of the FLASH Effect. Horst F et al. International Journal of Radiation Oncology Biology and Physics 115 (2023) 1006-1007.
Tumour irradiation in mice with a laser-accelerated proton beam. Kroll F et al. Nature Physics 18 (2022) 316-22.
Changes in Radical Levels as a Cause for the FLASH effect: Impact of beam structure parameters at ultra-high dose rates on oxygen depletion in water. Jansen J et al. Radiotherapy and Oncology 175 (2022) 193-19.
Beam pulse structure and dose rate as determinants for the flash effect observed in zebrafish embryo. Karsch L et al. Radiotherapy and Oncology 173 (2022) 49-54.
Normal tissue proton radiobiology
Although proton therapy is widely applied in cancer treatment some remaining questions on the biological effects, especially in normal tissue remain not fully understood. Together with the groups of Translational Radiooncology and Clinical Radiotherapy and Laser-Radiooncology at Oncoray our team established and further developed small-animal studies at the experimental proton beamline. Currently, a commercial small animal imaging and photon irradiation device is being connected to the proton beam line to facilitate CT image-guided proton irradiation in future.
Slice2Volume: Fusion of multimodal medical imaging and light microscopy data of irradiation-injured brain tissue in 3D. Soltwedel J et al. Radiotherapy and Oncology 182 (2023) 109591.
Combined proton radiography and irradiation for high-precision preclinical studies in small animals. Schneider M et al. Frontiers in Oncology 12 (2022) 982417.
Late side effects in normal mouse brain tissue after proton irradiation. Suckert T et al. Frontiers in Oncology 10 (2021) 598360.
MSc Moritz Schneider (M.Schneider(at)hzdr.de)
MSc Manuel Bernabei (M.Bernabei(at)hzdr.de)
Elisabeth Leßmann (E.Lessmann(at)hzdr.de)