STUDY ON CYTOTOXIC EFFECTS OF AUGER ELECTRON EMITTER TECHNETIUM-99M IN FUNCTIONAL RAT THYROID CELLS

Introduction: Because of its favorable half-life (6.02 hours) and distinct characteristic gamma-line, Technetium-99m (99mTc) is the most widespread radionuclide in nuclear medicine. Additionally, this nuclide emits low energetic, short-range Auger electrons which can deposit relatively high energy in a rather small volume in the immediate vicinity of the decay site. When located in close proximity to the DNA, the biological effects caused by Auger emitters are severe and assumed to be comparable with alpha particles. This poses the question towards an enhanced relative biological effectiveness (RBE) of Auger electron emitter. To assess the potential impact of 99mTc-Pertechnetate on cellular level, the cytotoxicity of 99mTc was investigated after extracellular and intracellular localization in the functional rat thyroid cell line, FRTL-5.Methods: FRTL-5 cells were exposed to 99mTc-pertechnetate (25, 50 and 75 MBq), either intra- or extracellular located and clonogenic assay (colony-forming assay, CFA) was performed to assess cell killing i.e. loss of reproductive capacity. For comparison FRTL-5 cells were externally irradiated with 137Cs (0.7 Gy/min; Gammacell-40). To achieve extracellular localization of 99mTc, the Sodium-Iodide Symporter (NIS) was inhibited with sodium perchlorate (SP). The used amounts of activity and the cellular uptake of 99mTc was measured and determined by gamma-counting. The micro-dosimetric calculations were based on cell size and Point-Kernel calculations using electron spectra provided and published by Pomplun et al (2006).Results: Rapid uptake of 99mTc by the FRTL-5 cells was observed within the first few minutes after application. The addition of SP restricted 99mTc from entering the intracellular lumen by the NIS. However, no complete inhibition of uptake as well as no elimination of intracellular 99mTc by extensive washing steps before CFA was observed, both much in contrast to reports of other authors (Wendisch et al. 2012). 99mTc was able to cause more prominent cell killing when located intracellular as compared to extracellular localization per decay. However, per dose unit no significant differences were observed. Compared to high-dose rate external 137Cs gamma-irradiation the cell killing was much weaker after 99mTc-exposure as already published for MN induction in SCL-II cells by Kriehuber et al. 2004. The SP treatment itself had no influence on cytotoxic damage.Conclusions: No significant effect of the localization (intra- vs extracellular) of 99mTc on cell killing can be observed per unit dose ruling out any “Auger effect” for 99mTc-pertechnetate. Furthermore, the cytotoxic effect of 99mTc is much weaker when compared to external high-dose rate exposure (137Cs), which is most likely to be explained by the low dose rate of the 99mTc exposure