title: Sodium-iodide symporter positive cells after intracellular uptake of (99m)Tc versus α-emitter 211At. Reduction of clonogenic survival and characterization of DNA damage.
abstract: OBJECTIVE
  We evaluated the DNA damaging potential of Auger electrons emitted in the decay of (99m)Tc compared to α-particles of 211At.
  
  
  METHODS
  The impact of (99m)Tc and 211At was monitored in a NIS-expressing rat thyroid cell model PCCl3 with varying, yet defined intra- and extracellular radionuclide distribution (using ± perchlorate). The radiotoxicity of (99m)Tc and 211At was studied by the comet assay under neutral and alkaline conditions and colony formation.
  
  
  RESULTS
  In the presence of perchlorate, the radioactivity yielding 37% cellular survival, A37, was estimated to be (0.27 ± 0.02) MBq/ml and (450 ± 30) MBq/ml for 211At and (99m)Tc, respectively. In absence of perchlorate, cellular radiotracer uptake was similar for both radionuclides (2.2%, 2.7%), yet the A37 was reduced by 82% for the α-emitter and by 95% for (99m)Tc. Cellular dose increased by a factor of 5 (211At) and 38 (99mTc). Comet assays revealed an increased DNA damage after intracellular uptake of both radiotracers.
  
  
  CONCLUSIONS
  The data indicate damage to the cell to occur from absorbed dose without recognizable contribution from intracellular heterogeneity of radionuclide distribution. Comet assay under alkaline and neutral conditions did not reveal any shift to more complex DNA damage after radionuclide uptake. Cellular uptake of (99m)Tc and 211At increased cellular dose and reduced clonogenic survival.
authors.affiliation: Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Dresden, Germany. joerg.kotzerke@mailbox.tu-dresden.de
authors.forename: J
authors.initials: J
authors.lastname: Kotzerke
authors.forename: M
authors.initials: M
authors.lastname: Wendisch
authors.forename: R
authors.initials: R
authors.lastname: Freudenberg
authors.forename: R
authors.initials: R
authors.lastname: Runge
authors.forename: L
authors.initials: L
authors.lastname: Oehme
authors.forename: G J
authors.initials: GJ
authors.lastname: Meyer
authors.forename: L A
authors.initials: LA
authors.lastname: Kunz-Schughart
authors.forename: G
authors.initials: G
authors.lastname: Wunderlich
mesh_terms: D000818:Animals; D001246:Astatine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D004249:DNA Damage / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004583:Electrons; D011829:Radiation Dosage; D051381:Rats; D027981:Symporters / Q000378:metabolism*; D013667:Technetium / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013961:Thyroid Gland / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D000099209:Sodium-Iodide Symporters
chemical_list: D001246:Astatine; D027981:Symporters; D013667:Technetium; D000099209:Sodium-Iodide Symporters