ESTRO 2022

Session Item

Saturday

May 07

10:30 - 11:30

Auditorium 12

Normal tissue radiobiology

Chair: , Denmark;

Co-Chair: , The Netherlands

Session Code: 1210

Session Type: Proffered Papers

Track: Radiobiology

10:30 - 10:40

Beam pulse structure affects the magnitude of Flash effect in zebrafish embryo

Elke Beyreuther, Germany

Presentation Number: OC-0094

Abstract

Abstract Title:

Beam pulse structure affects the magnitude of Flash effect in zebrafish embryo

Authors:

Elke Beyreuther^1,2, Jörg Pawelke^3,4, Michael Brand⁵, Stefan Hans⁵, Katalin Hideghéty^6,7, Jeanette Jansen^8,9, Leonhard Karsch^2,4, Elisabeth Lessmann¹, Steffen Löck^10,11,12, Michael Schürer¹³, Joao Seco^14,9, Emilia Rita Szabo¹⁵, Ulrich Schramm¹⁶

¹Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiation Physics, Dresden, Germany; ²Oncoray - National Center for Radiation Research in Oncology, Laser-Radiooncology, Dresden, Germany; ³Oncoray - National Center for Radiation Research in Oncology, Laser-Radiooncology , Dresden, Germany; ⁴Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany; ⁵Technische Universität Dresden, Center for Regenerative Therapies TU Dresden and Cluster of Excellence 'Physics of Life',, Dresden, Germany; ⁶University of Szeged, Oncotherapy Department, Szeged, Hungary; ⁷ELI-HU Non-Profit Ltd, ELI Alps, Szeged, Hungary; ⁸German Cancer Research Center, Division of Biomedical Physics in Radiation Oncology, Heidelberg, Germany; ⁹Ruprecht-Karls-University Heidelberg, Faculty of Physics and Astronomy, Heidelberg, Germany; ¹⁰Oncoray - National Center for Radiation Research in Oncology, Modeling and Biostatistics in Radiation Oncology, Dresden, Germany; ¹¹Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Department of Radiotherapy and Radiation Oncology, Dresden, Germany; ¹²German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, German Cancer Consortium (DKTK), Partner Site Dresden, Dresden, Germany; ¹³German Cancer Research Center, National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany; ¹⁴German Cancer Research Center, Division of Biomedical Physics in Radiation Oncology, Dresden, Germany; ¹⁵ELI-HU Non-Profit Ltd, ELI Alps, Szeged, Hungary; ¹⁶Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiation Physics , Dresden, Germany

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Purpose or Objective

In a previous experiment at the HZDR research electron accelerator ELBE the combination of ultra-high dose rates (UHDR) of 2.5x10⁵ Gy/s, delivered in a single pulse of 111 µs, and low partial oxygen pressure (≤ 5 mmHg) protected zebrafish embryo from radiation damage compared to continuous reference irradiation (mean dose rate of 0.11 Gy/s) and higher oxygen pressure (Pawelke et al. Radiother Oncol 2021). However, the influence of the beam pulse structure on the Flash effect remained unanswered and was studied in the present contribution.

Material and Methods

In addition to the UHDR regime already studied, the ELBE accelerator was used to mimic UHDR irradiation with the pulse structure of a clinical electron linac delivering a dose of 28 Gy by 5 pulses at a frequency of 250 Hz (irradiation time 164 ms). Furthermore, a third UHDR regime of similar mean dose rate, but continuous beam (280 Gy/s) mimicking Flash irradiation at an isochronous proton cyclotron (Beyreuther et al. Radiother Oncol 2019) was applied. For comparison, continuous reference irradiation of conventional, low dose rate was performed. Wild type zebrafish embryo (24 hpf) were irradiated and radiation induced malformations (edema, spinal curvature, altered body length and eye diameter) and embryo survival were studied during the four day follow up for all regimes. Differences in these endpoints between the four regimes were assessed using multivariable linear regression analyses. Zebrafish embryo irradiation was performed under low oxygen pressure and, in addition, the depletion of oxygen during irradiation was measured online.

Results

Compared to the reference regime, a protecting Flash effect was found for all UHDR pulse regimes for all endpoints, except embryo survival. Analysing radiation-induced malformations in more detail, significant correlations to mean and pulse dose rate were revealed. Surprisingly, the beam delivery by several macro pulses (Linac regime) reduced the Flash effect relative to delivery at the same pulse dose rate in one macro pulse.

Conclusion

The ELBE electron accelerator can be applied to study the influence of pulse structure on the Flash effect by varying the pulse sequence, length and dose rate over several orders of magnitude. The results of this work confirm the previous findings and, furthermore, show that the FLASH effect should be observed at UHDR at clinical electron and proton facilities.