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@ARTICLE{Dokic:177231,
      author       = {I. Dokic$^*$ and J. Bojcevski$^*$ and D. Walsh$^*$ and S.
                      Mein$^*$ and C. Wang$^*$ and H. K. Liu$^*$ and S. Brons and
                      T. Haberer and J. Debus$^*$ and A. Mairani and A.
                      Abdollahi$^*$},
      title        = {{C}arbon {I}on {FLASH} {D}ose-{R}ate {R}adiotherapy:
                      {F}irst {I}nvestigation in {H}uman {B}rain {O}rganoids.},
      journal      = {International journal of radiation oncology, biology,
                      physics},
      volume       = {111},
      number       = {3S},
      issn         = {0360-3016},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2021-02365},
      pages        = {e231},
      year         = {2021},
      note         = {#EA:E210#LA:E210#},
      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.},
      cin          = {E210 / HD01 / A240 / E050},
      ddc          = {610},
      cid          = {I:(DE-He78)E210-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)A240-20160331 / I:(DE-He78)E050-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34700969},
      doi          = {10.1016/j.ijrobp.2021.07.791},
      url          = {https://inrepo02.dkfz.de/record/177231},
}