Background and Aims

In a recent experiment at the HZDR research electron accelerator ELBE the influence of dose rate and partial oxygen pressure on the Flash effect was studied in a zebrafish embryo model. High mean electron dose rates of 10⁵ Gy/s (max regime) and partial oxygen pressure below 5 mmHg were found to protect zebrafish embryo from radiation damage compared to continuous reference irradiation (0.11 Gy/s) and higher oxygen pressure (Pawelke et al. Radiother Oncol 2021). However, the influence of beam pulse structure remains unanswered in this experiment.

Methods

In addition to the above mentioned two pulse regimes, the ELBE accelerator was used to mimic the pulse structure of a clinical electron linac delivering a dose of 28 Gy by 5 pulses at a frequency of 250 Hz. For comparison, a fourth regime of similar mean dose rate, but continuous beam (280 Gy/s) mimicking Flash irradiation at a proton isochronous cyclotron (Beyreuther et al. Radiother Oncol 2019) was applied.

Results

First results indicate a clear difference between the "max regime" and the other three electron pulse regimes. Further analysis is under way and the results for different endpoints will be presented.

Conclusions

The ELBE electron accelerator can be applied to study the influence of beam dose rate and pulse structure on the Flash effect by varying both parameters over several orders of magnitude. Hence, it is the ideal tool for systematic studies on optimal electron beam parameters for Flash.

This work was supported by EMPIR 18HLT04UHDpulse project.

Background and Aims

The recent rediscovery of the “Flash-effect” revived the interest in high dose-rate radiation effects throughout the radiobiology community, promising protection of normal tissue, while simultaneously not altering tumour control. Systematic preclinical studies resulted in a “recipe” of necessary beam parameters for inducing an electron Flash effect (https://doi.org/10.3389/fonc.2019.01563). For protons, the Flash effect was confirmed in a few animal experiments using the beam parameters available at clinical cyclotrons. Extending the clinical parameter range, the “Dresden platform for high-dose rate radiobiology” enables proton experiments with dose-rates of up to 10⁹ Gy/s.

Methods

The general applicability of the different proton beams for radiobiological studies was proven using biological models of increasing complexity, from cellular models to zebrafish embryo to mouse, at the Draco laser accelerator and, for comparison, at the University Proton Therapy Dresden (UPTD).

Results

A proof-of-principle irradiation campaign was performed using a mouse ear tumour model (https://doi.org/10.1371/journal.pone.0177428) to study the effects of the continuous beam delivery at UPTD and the pulsed beam delivery at Draco with peak dose-rates of 10⁸ Gy/s. Moreover, to investigate the interplay of oxygen consumption and proton dose-rate up to 300 Gy/s and 10⁹ Gy/s, respectively, were applied at UPTD and Draco to study the radiation response of zebrafish embryos.

Conclusions

The successful performance of comparison experiments at Draco laser accelerator and UPTD cyclotron paves the way for upcoming in vivo experiments at both machines. At the conference, we will provide an overview of our radiobiological experiments and the obtained results.