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@INPROCEEDINGS{Kriehuber:837956,
      author       = {Kriehuber, Ralf and Unverricht, Marcus and Oskamp, Dominik
                      and Pomplun, Ekkehard},
      title        = {{S}tudy {O}n {T}he {R}adiotoxicity {O}f {T}he {A}uger
                      {E}lectron {E}mitter {T}echnetium-99m {I}n {F}unctional
                      {R}at {T}hyroid {C}ells},
      reportid     = {FZJ-2017-06717},
      year         = {2016},
      abstract     = {Introduction: Because of its favorable half-life (6.02
                      hours) and distinct characteristic gamma-ray line,
                      Technetium-99m (Tc-99m) is the most widespread radionuclide
                      in nuclear medicine. Additionally, this nuclide emits low
                      energetic, short-range Auger electrons which can deposit
                      large amounts of energy in a rather small volume in the
                      immediate vicinity of the decay site. When located in close
                      proximity to the DNA, the biological effects caused by Auger
                      emitters are severe and comparable to high-LET radiation.
                      This poses the question towards an increased relative
                      biological effectiveness (RBE) of the Auger electron emitter
                      Tc-99m. To assess the potential impact of
                      Tc-99m-Pertechnetate on cellular level, DNA double-strand
                      breaks (gammaH2AX assay) and cell killing (colony forming
                      assay) was investigated after extracellular and
                      intracellular localization of Tc-99m in the functional rat
                      thyroid cell line, FRTL-5 and effects were compared to high
                      dose-rate external uniform γ-irradiation (Cs-137; 0.7
                      Gy/min).Material and methods: FRTL-5 cells were ex-posed to
                      25, 50 and 75 MBq Tc-99m pertechne-tate. Extracellular
                      localization of Tc-99m was achieved by inhibiting the
                      Sodium-Iodide Sym-porter (NIS) with sodium perchlorate (SP).
                      Standard Colony Forming Assay was employed. GammaH2AX
                      staining was achieved using a mouse anti-phospho H2AX
                      antibody (Clone JBW301, Invitrogen). External high dose-rate
                      γ-irradiation was performed with a Cs-137 source (GammaCell
                      40). Cell number and Tc-99m uptake was determined in each
                      individual experiment (CASY® Schärfe System; Gamma
                      Counter, Wallace 3" PerkinElmer). Dosimetry at cellular
                      level was based on cell size and point kernel calculations
                      using electron spectra provided and published by Pomplun et
                      al. 2006 [1].Results: A rapid cellular uptake of Tc-99m in
                      FRTL-5 cells was observed. Inhibtion of NIS re-stricted the
                      uptake efficiently. However, no complete inhibition of
                      uptake was observed. GammaH2AX-foci induction was somewhat
                      higher per dose unit when Tc-99m was located intracellular.
                      Tc-99m induced more prominent cell killing when located
                      intracellular as compared to extracellular localization per
                      decay. However, per dose unit no significant differences
                      were observed (Figure 1). Compared to high dose rate
                      external γ-irradiation GammaH2AX-foci induction as well as
                      cell killing was much weaker after Tc-99m-exposure as
                      already published for cell killing and micronucleus
                      induction in SCL-II cells by Kriehuber et al., 2004 [2]. SP
                      treatment itself had no influence on cytotoxic
                      damage.Conclusions: No significant effect on cell killing
                      due to the localization (intra- vs extracellular) of Tc-99m
                      was observed per unit dose ruling out any Auger
                      electron-associated enhanced cytotoxicity for Tc-99m
                      pertechnetate. The cytotoxic effect of Tc-99m and
                      GammaH2AX-foci induction is much weaker when compared to
                      external high dose rate γ-exposure, which is most likely
                      explained by the low dose rate of the Tc-99m exposure.
                      Figure 1. Cell survival of FRTL-5 cells as measured in the
                      colony forming assay. Survival fraction (SF) as a function
                      of cellular radiation dose revealed no significant
                      differences in cell survival between cells with (filled
                      diamonds) and without (open diamonds) Tc-99m uptake.
                      External homogenous high dose-rate γ-irradiation (Cs-137
                      exposure, dose rate 0.7 Gy/min, circles) was 4 to 7 times
                      more efficient in cell killing when compared to Tc-99m
                      exposed cells (diamonds).References: 1. Estimation of a
                      radiation weighting factor for 99mTc (E. Pomplun et al.),
                      Radiat. Prot. Dosimetry 122, 80-81 (2006)2. Study on cell
                      survial, induction of apoptosis and micronucleus formation
                      in SCL-II cells after exposure to the Auger electron emitter
                      (99m)Tc (R. Kriehuber et al.), Int. J Radiat. Biol. 80,
                      875-880 (2004)},
      month         = {Mar},
      date          = {2016-03-20},
      organization  = {14th International Workshop of
                       Radiation Damage to DNA, Melbourne
                       (Australia), 20 Mar 2016 - 24 Mar 2016},
      subtyp        = {Invited},
      cin          = {S-US},
      cid          = {I:(DE-Juel1)S-US-20090406},
      pnm          = {899 - ohne Topic (POF3-899)},
      pid          = {G:(DE-HGF)POF3-899},
      typ          = {PUB:(DE-HGF)6},
      url          = {https://juser.fz-juelich.de/record/837956},
}