On the dose calculation at the cellular level and its implications for the RBE of99mTc and123I

Purpose: Based on the authors’ previous findings concerning the radiotoxicity of99mTc, the authors compared the cellular survival under the influence of this nuclide with that following exposure to the Auger electron emitter 123I. 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 either99mTc or 123I 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 99mTc (D37 = 3.5 Gy), and 123I (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 99mTc and 12.4 times lower for 123I 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 99mTc and RBE = 3.43 for 123I. Meanwhile, regarding the dose to the entire cell, RBE = 0.75 for 99mTc and RBE = 1.87 for 123I. 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 99mTc and (221 ± 82) decays/MBq for 123I. 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 for99mTc and 123I 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.