Natrium-Iodid-Symporter-positive Zellen nach intrazellulärer Aufnahme von 99mTc im Vergleich zum α-Emitter 211At – Reduktion des klonogenen Überlebens und Charakterisierung von DNA-Schäden

Purpose: We evaluated the DNA damaging potential of Auger electrons emitted in the decay of 99mTc compared to α-particles of 211At. Material and methods: The impact of 99mTc and 211At was monitored in a NIS-expressing rat thyroid cell model PCCl3 with varying, yet defined intra- and extracellular radionuclide distribution (using ± perchlorate). The radiotoxicity of 99mTc and 211At 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, A37, was estimated to be (0.27±0.02) MBq/ml and (450±30) MBq/ml for 211At and 99mTc, respectively. In absence of perchlorate, cellular radiotracer uptake was similar for both radionuclides (2.2%, 2.7%), yet the A37 was reduced by 82% for the α-emitter and by 95% for 99mTc. Cellular dose increased by a factor of 5 (211At) and 38 (99mTc). Comet assays revealed an increased DNA damage after intracellular uptake of both radiotracers. 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 99mTc and 211At increased cellular dose and reduced clonogenic survival.