Presenter of 1 Presentation
LASER-DRIVEN PROTON ACCELERATION AT DRACO PW: A NOVEL PLATFORM FOR ULTRA-HIGH DOSE RATE RADIOBIOLOGY.
Abstract
Background and Aims
After the rediscovery of the normal tissue sparing FLASH effect of high dose rate radiation, research activities on this topic have been revived. But especially for protons, the portfolio of accelerators capable of performing studies at ultra-high dose rates is limited. Laser-plasma accelerators (LPA) can generate extremely intense proton bunches of many 10 MeV kinetic energy. In combination with dedicated dose delivery systems, LPA proton sources facilitate peak dose rates well above 108 Gy/s in a pulse structure regime complementary to conventional accelerators.
Methods
The reliable generation of proton spectra beyond 60 MeV at DRACO-PW [Ziegler et al, SciRep2021], combined with a dedicated energy selective pulsed magnet beam transport system [Brack et al, SciRep2020], allows tailored sample-specific dose distributions. Adapted on-shot dosimetry enables the required spectral monitoring of every proton bunch. Two irradiation series on volumetric biological samples were performed at DRACO-PW, accompanied by reference irradiations at the University Proton Therapy Dresden.
Results
The first small animal pilot study at a laser-driven proton source was conducted successfully. The mouse-ear tumor model’s requirements [Beyreuther et al, PLoS One2018] were fulfilled and verified at high precision (+/- 5%) concerning predefined dose value and conformity. Complementary, a study investigating dose-rate effects such as FLASH was performed irradiating zebrafish embryos with above 109 Gy/s.
Conclusions
We present a laser-based irradiation platform at the DRACO-PW facility that enables systematic radiobiological studies, laying the foundations for further studies at LPA sources exploring ultra-high dose-rate effects, such as FLASH, over previously unreachable parameter space.
Author Of 3 Presentations
ULTRA-HIGH DOSE RATE PROTON RADIOBIOLOGY AT THE “DRESDEN PLATFORM FOR HIGH DOSE-RATE RADIOBIOLOGY”
Abstract
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.
OXYGEN DEPLETION IN ULTRA-HIGH DOSE RATES FOR PROTONS AND ELECTRONS: EXPERIMENTAL APPROACH IN WATER AND BIOLOGICAL SAMPLES
Abstract
Background and Aims
In FLASH radiotherapy (RT), a protective effect of healthy tissue was observed, while tumor control remains comparable to conventional RT. One possible explanation is the oxygen depletion hypothesis, in which radiolysis of water/cytoplasma causes the production of radicals that then react with O2 dissolved in water. This would cause a reduction in O2, which results in a hypoxic target and thus a radio-protective effect. In a previous study (Jansen et al. 2021), we measured O2 depletion using an optical sensor in sealed water phantoms during irradiation at high dose rates (<300 Gy/s) for protons, carbon ions and photons.
Methods
In the study presented here, this experiment was conducted further to ultra-high dose rates (10^9 Gy/s) with protons at DRACO and electrons at ELBE, where also the impact of different pulse structures on O2 depletion in water was tested. In addition, various settings were tested in order to irradiate zebrafish embryos with FLASH while simultaneously measuring O2.
Results
We were able to confirm the results of our previous study even at ultra-high dose rates and with electrons. Furthermore, it was possible to measure O2 depletion during zebrafish embryo irradiation making a simultaneous study of biological response and O2 depletion possible.
Conclusions
Not enough O2 was depleted at clinical doses to explain a FLASH effect based on radiation-induced hypoxia. The amount of O2 depleted per dose depends on dose rate, and higher dose rates deplete slightly less O2. The experimental set up allows for future joint experiments of biological samples and oxygen monitoring.
LASER-DRIVEN PROTON ACCELERATION AT DRACO PW: A NOVEL PLATFORM FOR ULTRA-HIGH DOSE RATE RADIOBIOLOGY.
Abstract
Background and Aims
After the rediscovery of the normal tissue sparing FLASH effect of high dose rate radiation, research activities on this topic have been revived. But especially for protons, the portfolio of accelerators capable of performing studies at ultra-high dose rates is limited. Laser-plasma accelerators (LPA) can generate extremely intense proton bunches of many 10 MeV kinetic energy. In combination with dedicated dose delivery systems, LPA proton sources facilitate peak dose rates well above 108 Gy/s in a pulse structure regime complementary to conventional accelerators.
Methods
The reliable generation of proton spectra beyond 60 MeV at DRACO-PW [Ziegler et al, SciRep2021], combined with a dedicated energy selective pulsed magnet beam transport system [Brack et al, SciRep2020], allows tailored sample-specific dose distributions. Adapted on-shot dosimetry enables the required spectral monitoring of every proton bunch. Two irradiation series on volumetric biological samples were performed at DRACO-PW, accompanied by reference irradiations at the University Proton Therapy Dresden.
Results
The first small animal pilot study at a laser-driven proton source was conducted successfully. The mouse-ear tumor model’s requirements [Beyreuther et al, PLoS One2018] were fulfilled and verified at high precision (+/- 5%) concerning predefined dose value and conformity. Complementary, a study investigating dose-rate effects such as FLASH was performed irradiating zebrafish embryos with above 109 Gy/s.
Conclusions
We present a laser-based irradiation platform at the DRACO-PW facility that enables systematic radiobiological studies, laying the foundations for further studies at LPA sources exploring ultra-high dose-rate effects, such as FLASH, over previously unreachable parameter space.