Journal Article

DKFZ-2021-02365

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Carbon Ion FLASH Dose-Rate Radiotherapy: First Investigation in Human Brain Organoids.

Dokic, I. (First author)DKFZ* ; Bojcevski, J.DKFZ* ; Walsh, D.DKFZ* ; Mein, S.DKFZ* ; Wang, C.DKFZ* ; Liu, H. K.DKFZ* ; Brons, S. ; Haberer, T. ; Debus, J.DKFZ* ; Mairani, A. ; Abdollahi, A. (Last author)DKFZ*

2021
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.ijrobp.2021.07.791

Abstract: In this work, we investigated and compared the effects of carbon ion ultra-high dose-rate (uHDR; FLASH) vs standard dose-rate (SDR) beams on brain organoids.For testing the effects of high dose-rate radiotherapy using carbon ions, dose rates of ∼40 Gy/s (uHDR) and 0.15 Gy/s (SDR) were applied at 7.4 Gy dose (LETd = 12 keV µm-1). The effectiveness of uHDR vs. SDR carbon ion beams was tested using brain organoids generated from human induced pluripotent stem cells (iPS). Brain organoids were evaluated for their cellular composition and radiation induced DNA-damage repair using immunofluorescence. Quantitative analysis was performed using semi-automated imaging software.Multicellular brain organoids were characterized by the presence of neuronal progenitor cells (nestin positive), more differentiated neurons (Tuj1 positive), and astrocytic cells (GFAP positive). Following irradiation, the cells were further evaluated for presence of radiation induced DNA double strand breaks surrogated by nuclear γH2AX foci (RIF). While both uHDR and SDR irradiations led to RIF formation, uHDR markedly expressed reduced RIF vs. SDR at 1-hour post-irradiation.This study indicates feasibility of brain organoids as a healthy brain tissue model for studying the effects of particle radiation. Here reported encouraging normal tissue sparing effect of uHDR carbon ion beams, at relevant plateau LET level, warrants further investigation of carbon ion FLASH radiotherapy.

Note: #EA:E210#LA:E210#

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Contributing Institute(s):

1. E210 Translationale Radioonkologie (E210)
2. DKTK HD zentral (HD01)
3. A240 Molekulare Neurogenetik (A240)
4. E050 KKE Strahlentherapie (E050)

Research Program(s):

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

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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