Dissertation / PhD Thesis

DKFZ-2021-02534

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Oxygen Effects in (FLASH-) Radiotherapy on a Radiochemical and Genetic Level

Jansen, J.DKFZ*

2021

Abstract: In radiotherapy, oxygen acts as strong radiosensitizer and alters cellular responseto radiation drastically. Especially, the e‚ect of the so-called FLASH radiotherapy,which applies high dose rates above 40 Gy/s to spare healthy tissue from radiationdamage, is inƒuenced by oxygen. At high O2levels the protective e‚ect of FLASH isdecreased in vivo. ‘e underlying mechanisms are not completely understood yet.In this thesis, oxygen e‚ects were investigated on (i) a radiochemical level by oxygen depletion measurements in water phantoms and together with cancer cells, (ii)on a genetic level developing a novel analysis method on gene expression pa‹ernsand (iii) on a mechanistic, radical scavenging level by modulating cellular defense.It was found, that a popular hypothesis for explaining the FLASH e‚ect, the oxygendepletion hypothesis, cannot be solely responsible for the observed altered cellularresponse a‰er FLASH through radiation induced hypoxia alone. However, radicalconcentrations are highly dependent on dose rate and beam pulse structure implyingpotential biological impact. Radical scavenging systems in cells were found to be altered using SOD-mimicking CuL/FeL compounds leading to a decrease of metastaticpotential. ‘e results strengthen the link between FLASH e‚ects and radical levels,inƒuenced by radical scavenging systems in cancer cells and oxygen conditions.

Note: Corresponding author J. Seco
Note: Dissertation, Universität Heidelberg, 2021

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Contributing Institute(s):

1. E041 Medizinische Physik in der Radioonkologie (E041)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2021

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