Sodium-Iodide Symporter Positive Cells After Intracellular Uptake Of Tc-99m Versus Alpha-Emitter At-211 Reduction Of Clonogenic Survival And Characterization Of Dna Damage

Purpose: We evaluated the DNA damaging potential of Auger electrons emitted in the decay of Tc-99m compared to a-particles of At-211. Material and methods: The impact of Tc-99m and At-211 was monitored in a NIS-expressing rat thyroid cell model PC CI3 with varying, yet defined intra- and extracellular radionuclide distribution (using +/- perchlorate). The radiotoxicity of Tc-99m and At-211 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, A(37), was estimated to be (0.27 +/- 0.02) MBq/ml and (450 +/- 30) MBq/ml for At-211 and Tc-99m, respectively. In absence of perchlorate, cellular radiotracer uptake was similar for both radionuclides (2.2%, 2.7%), yet the A(37) was reduced by 82% for the alpha-emitter and by 95% for Tc-99m. Cellular dose increased by a factor of 5 (At-211) and 38 (Tc-99m). Comet assays revealed an increased DNA damage after intracellular uptake of both radio-tracers. 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 Tc-99m and At-211 increased cellular dose and reduced clonogenic survival.