ESTRO 2022 - Abstract Book

S70

Abstract book

ESTRO 2022

In a previous experiment at the HZDR research electron accelerator ELBE the combination of ultra-high dose rates (UHDR) of 2.5x10 5 Gy/s, delivered in a single pulse of 111 µ s, 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. Materials 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. I. Martínez-Rovira 1 , O. Seksek 2 , J. Bergs 3 , R. Hirayama 4 , N. Matsufuji 4 , T. Inaniwa 4 , S. Koike 4 , T. Shimokawa 4 , Y. Prezado 5 , I. Yousef 6 1 Universitat Autònoma de Barcelona , Physics Department, Cerdanyola del Vallès, Spain; 2 Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Orsay, France; 3 Charité - Universitätsmedizin Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany; 4 National Institutes for Quantum Science and Technology (QST), National Institutes for Quantum Science and Technology (QST), Chiba, Japan; 5 Institut Curie, Institut Curie, Orsay, France; 6 ALBA Synchrotron, ALBA Synchrotron, Cerdanyola del Vallès, Spain Purpose or Objective Due to their increased linear energy transfer, very heavy ions, like neon, provide a reduced oxygen enhancement effect. This could benefit the treatment of hypoxic tumours, which remains one of the major challenges in radiotherapy. However, clinical results in the 80’s led to adverse effects in healthy tissues and thus, the use of those beams was discontinued. One possible strategy to overcome this limitation is to combine the prominent advantages of these very heavy ions and the remarkable tissue preservation provided by the spatial fractionation of the dose, as in minibeam radiotherapy (MBRT). In this work, we will investigate the biochemical mechanisms involved in healthy tissue response after Ne MBRT ( in vitro studies). For this purpose, we used the capabilities of synchrotron-based Fourier transform infrared microspectroscopy (SR- FTIRM) as a bio-analytical tool to elucidate the biological mechanisms induced by Ne MBRT at the molecular level and at a single-cell scale. Materials and Methods BJ human fibroblasts were irradiated using neon beams, in conventional and minibeam configurations, at the Heavy Ion Medical Accelerator in Chiba (HIMAC) of the National Institutes for Quantum Science and Technology (Japan). SR-FTIRM at ALBA Synchrotron (MIRAS beamline) was employed for examining composition and/or conformational changes in biomolecules, including proteins, lipids, carbohydrates, and nucleic acids. Principal Component Analysis (PCA) was performed using the Quasar software to evaluate the variations in the spectral features. Results SR-FTIRM experiments allowed the characterization of spectral signatures of treatment-induced effects. PCA results showed clear differences between BB and MBRT groups with respect to Control, as it can be seen in Figure 1. The analysis of the PCA loadings plots reveals that most of the variance accounting for the separation between the peak and valley MBRT, the BB and the control groups is related to conformational changes in secondary protein structures, as well as to complex DNA conformational changes and rearrangements. Differences in the vibrational features were dose and time-dependent (data not shown). OC-0095 Neon minibeam radiotherapy (Ne MBRT): investigating biological mechanisms with synchrotron light