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@INPROCEEDINGS{Dahmen:839895,
      author       = {Dahmen, Volker and Reiter, Stefan and Pomplun, Ekkehard and
                      Kriehuber, Ralf},
      title        = {{I}odine-125-labeled {DNA}-{T}riplex-forming
                      oligonucleotides reveal increased cyto- and genotoxic
                      effectiveness compared to {P}hosphorus-32 and external
                      γ-irradiation},
      reportid     = {FZJ-2017-07473},
      year         = {2014},
      abstract     = {Introduction: The efficacy of DNA-targeting radionuclide
                      therapies might be strongly enhanced by employing short
                      range particle emitter. To determine the gain of the
                      biological impact per decay and radiation dose the
                      biological effectiveness of the Auger electron emitter I-125
                      was investigated and compared to the ß--emitter P-32 as
                      well as to external homogeneous high dose rate
                      γ-irradiation.Methods: Triplex-forming oligonucleotides
                      (TFO) bind to the DNA double helix in a sequence specific
                      manner and are therefore a suitable carrier for Auger
                      electron emitter to damage exclusively targeted DNA
                      sequences [1]. Clonogenicity (colony-forming assay; CFA) and
                      induction of DNA double strand breaks (DSB; 53BP1 foci
                      assay) were investigated in SCL-II cells after exposure to
                      I-125- or P-32-labeled TFO for different numbers of
                      accumulated decays and were compared to external
                      γ-irradiation (Cs-137; 0.7 Gy/min). The used TFO targeted a
                      DNA sequence located in the glyceraldehyde 3-phosphate
                      dehydrogenase (GAPDH) gene. Point kernel calculations were
                      employed for dosimetry on subcellular level.Results:
                      I-125-labeled TFO were shown to induce a pronounced decrease
                      in cell survival and a marked increase of DSB with
                      increasing numbers of accumulated decays per cell. Reduction
                      in cell survival as measured in the CFA reached the D37
                      value at ~ 350 cumulated decays per cell, equivalent to ~
                      1.2 Gy cell nucleus dose. P-32 labeled TFO displayed a weak
                      cell killing ability and caused a small increase of 53BP1
                      foci up to ~ 4000 accumulated decays per cell, equivalent to
                      ~ 1 Gy cell nucleus dose. The impact of P-32 was comparable
                      to external γ-irradiation.Conclusions: The reduction of
                      cell survival and the increase of DNA damage proved to be
                      much more pronounced in I-125-TFO exposed cells in
                      comparison to P-32-labeled TFO per decay and per dose unit.
                      This finding might be well explained by the high number of
                      low energy Auger electrons emitted by I-125 per decay,
                      leading to a high ionization density in the immediate
                      vicinity of the decay site, probably producing highly
                      complex DNA lesions, overcharging the cellular DNA-damage
                      repair mechanism. The similar biological effectiveness of
                      P-32-TFO exposure and external γ-irradiation proves the
                      validity of the performed dose calculation on cellular
                      level.[1] Dahmen V, Kriehuber R. Int J Radiat Biol. 2012
                      Dec;88(12):972-9Funded by Bundesministerium für Bildung und
                      Forschung (BMBF), Grant 02NUK005A},
      month         = {Oct},
      date          = {2014-10-18},
      organization  = {Annual Congress of the European
                       Association of Nuclear Medicine,
                       Göteburg (Sweden), 18 Oct 2014 - 22
                       Oct 2014},
      subtyp        = {After Call},
      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/839895},
}