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On the dose calculation at the cellular level and its implications for the RBE of 99m Tc and 123 I
Author(s) -
Freudenberg R.,
Runge R.,
Maucksch U.,
Berger V.,
Kotzerke J.
Publication year - 2014
Publication title -
medical physics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 180
eISSN - 2473-4209
pISSN - 0094-2405
DOI - 10.1118/1.4876296
Subject(s) - relative biological effectiveness , radiochemistry , nuclear medicine , radionuclide , radionuclide therapy , dosimetry , absorbed dose , chemistry , radiobiology , clonogenic assay , nuclide , irradiation , physics , nuclear physics , cell , medicine , biochemistry
Purpose: 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 (D 37 = 2.6 Gy), the radionuclides 99m Tc (D 37 = 3.5 Gy), and 123 I (D 37 = 3.8 Gy) were less toxic in the presence of perchlorate. In the absence of perchlorate, the amount of activity a 37 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.