title: On the dose calculation at the cellular level and its implications for the RBE of (99m)Tc and ¹²³I.
abstract: OBJECTIVE
  Based on the authors' previous findings concerning the radiotoxicity of(99m)Tc, the authors compared the cellular survival under the influence of this nuclide with that following exposure to the Auger electron emitter (123)I. To evaluate the relative biological effectiveness (RBE) of both radionuclides, knowledge of the absorbed dose is essential. Thus, the authors present the dose calculations and discuss the results based on different models of the radionuclide distribution. Both different target volumes and the influence of the uptake kinetics were considered.
  
  
  METHODS
  Rat thyroid PC Cl3 cells in culture were incubated with either(99m)Tc or (123)I or were irradiated using 200 kV x-rays in the presence or absence of perchlorate. The clonogenic cell survival was measured via colony formation. In addition, the intracellular radionuclide uptake was quantified. Single-cell dose calculations were based on Monte Carlo simulations performed using Geant4.
  
  
  RESULTS
  Compared with external radiation using x-rays (D37 = 2.6 Gy), the radionuclides (99m)Tc (D37 = 3.5 Gy), and (123)I (D37 = 3.8 Gy) were less toxic in the presence of perchlorate. In the absence of perchlorate, the amount of activity a37 that was necessary to reduce the surviving fraction (SF) to 0.37 was 22.8 times lower for (99m)Tc and 12.4 times lower for (123)I because of the dose increase caused by intracellular radionuclide accumulation. When the cell nucleus was considered as the target for the dose calculation, the authors found a RBE of 2.18 for (99m)Tc and RBE = 3.43 for (123)I. Meanwhile, regarding the dose to the entire cell, RBE = 0.75 for (99m)Tc and RBE = 1.87 for (123)I. The dose to the entire cell was chosen as the dose criterion because of the intracellular radionuclide accumulation, which was found to occur solely in the cytoplasm. The calculated number of intracellular decays per cell was (975 ± 109) decays/MBq for (99m)Tc and (221 ± 82) decays/MBq for (123)I.
  
  
  CONCLUSIONS
  The authors' data indicate that extra-nuclear targets to Auger electrons exist, which is obvious from our dose calculations. When considering the dose to the cell nucleus, the authors found an enhanced RBE for(99m)Tc and (123)I relative to acute x-ray irradiation and pure extracellular irradiation with both radionuclides. Surprisingly, the authors did not find any radionuclide accumulation in the cell nucleus, indicating that there are additional radiosensitive targets besides the DNA. In addition, the authors demonstrated the necessity of cellular dose calculations in radiobiological experiments using unsealed radionuclides and identified the relevant parameters.
authors.affiliation: University Hospital/Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Department of Nuclear Medicine, Dresden, Saxony 01307, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Freudenberg
authors.affiliation: University Hospital/Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Department of Nuclear Medicine, Dresden, Saxony 01307, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Runge
authors.affiliation: University Hospital/Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Department of Nuclear Medicine, Dresden, Saxony 01307, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Maucksch
authors.affiliation: University Hospital/Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Department of Nuclear Medicine, Dresden, Saxony 01307, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Berger
authors.affiliation: University Hospital/Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Department of Nuclear Medicine, Dresden, Saxony 01307, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Kotzerke
mesh_terms: D065638:Absorption, Radiation; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects*; D003198:Computer Simulation; D003593:Cytoplasm / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D042541:Intracellular Space / Q000528:radiation effects; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics*; D008954:Models, Biological; D009010:Monte Carlo Method; D010472:Perchlorates / Q000494:pharmacology; D011829:Radiation Dosage; D011874:Radiometry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics*; D051381:Rats; D012062:Relative Biological Effectiveness; D013667:Technetium / Q000009:adverse effects / Q000493:pharmacokinetics*; D013961:Thyroid Gland; D014965:X-Rays / Q000009:adverse effects
chemical_list: D013956:Antithyroid Agents; D007457:Iodine Radioisotopes; D010472:Perchlorates; D019275:Radiopharmaceuticals; D013667:Technetium; C494474:perchlorate