title: [99mTc reduces clonogenic survival after intracellular uptake in NIS-positive cells in vitro more than 131I].
abstract: OBJECTIVE
  In addition to gamma radiation of 140 keV 99mTc emits during the transition to 99Tc electrons of low energy and tiny path-lengths. These Auger electrons cannot be utilized in diagnostic procedures. However, they were discussed frequently for therapeutic application. Hitherto proof of effect of the Auger electrons from 99mTc is missing which is supplied now in an in vitro-system in comparison to beta-emitter 131I.
  
  
  METHODS
  The thyroid cell line PCCl3 (sodium iodide symporter (NIS)-positive) was incubated with 131I-sodium iodide (131I) or 99mTc-pertechnetate (99mTc) in presence or absence of perchlorate. For comparison the amount of radioactivity was adjusted to obtain the same dose from extracellular irradiation for both radionuclides. The colony forming assay detects the clonogenic cell survival as surviving fraction. In addition, intracellular radionuclide uptake was quantified.
  
  
  RESULTS
  Dose effect curves were established for 131I and 99mTc for variable extra- and intracellular distribution of the radioactivity. In presence of perchlorate no cellular uptake of radioactivity was detectable. Survival curves were largely comparable confirming the dosimetric calculations. In absence of perchlorate cellular radiotracer uptake varied from 1.39% (131I) to 1.90% 99mTc). Effects on survival were twice for the beta-emitter and ten-fold higher for 99mTc.
  
  
  CONCLUSIONS
  Intracellular uptake of 131I and 99mTc increases DNA-damage compared to strict extracellular radiotracer distribution which was demonstrated by means of colony forming assay. Increasing radiotoxicity from intracellular 99mTc is explained most likely by increased dose deposition in cellular structures due to Auger- and conversion-electrons of low range and high local energy deposition.
authors.affiliation: Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wendisch
authors.forename: R
authors.initials: R
authors.lastname: Freudenberg
authors.forename: J
authors.initials: J
authors.lastname: Drechsel
authors.forename: R
authors.initials: R
authors.lastname: Runge
authors.forename: G
authors.initials: G
authors.lastname: Wunderlich
authors.forename: J
authors.initials: J
authors.lastname: Kotzerke
mesh_terms: D001692:Biological Transport; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000494:pharmacology*; D012974:Sodium Iodide / Q000378:metabolism; D013670:Sodium Pertechnetate Tc 99m / Q000493:pharmacokinetics / Q000494:pharmacology*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects
chemical_list: D007457:Iodine Radioisotopes; D013670:Sodium Pertechnetate Tc 99m; D012974:Sodium Iodide