Reduction in clonogenic survival of sodium-iodide symporter (NIS)-positive cells following intracellular uptake of 99mTc versus 188Re

Abstract

Purpose: Cellular radionuclide uptake increases the heterogeneity of absorbed dose to biological structures. Dose increase depends on uptake yield and emission characteristics of radioisotopes. We used an in vitro model to compare the impact of cellular uptake of 188Re-perrhenate and 99mTc-pertechnetate on cellular survival.Materials and methods: Rat thyroid PC Cl3 cells in culture were incubated with 188Re or 99mTc in the presence or absence of perchlorate for 1 hour. Clonogenic cell survival was measured by colony formation. In addition, intracellular radionuclide uptake was quantified.Results: Dose effect curves were established for 188Re and 99mTc for various extra- and intracellular distributions of the radioactivity. In the presence of perchlorate, no uptake of radionuclides was detected and 188Re reduced cell survival more efficiently than 99mTc. A37, the activity that is necessary to yield 37% cell survival was 14 MBq/ml for 188Re and 480 MBq/ml for 99mTc. In the absence of perchlorate, both radionuclides showed similar uptakes; however, A37 was reduced by 30% for the beta-emitter and by 95% for 99mTc. The dose D37 that yields 37% cell survival was between 2.3 and 2.8 Gy for both radionuclides.Conclusions: Uptake of 188Re and 99mTc decreased cell survival. Intracellular 99mTc yielded a dose increase that was higher compared to 188Re due to emitted Auger and internal conversion-electrons. Up to 5 Gy there was no difference in radiotoxicity of 188Re and 99mTc. At doses higher than 5 Gy intracellular 99mTc became less radiotoxic than 188Re, probably due to a non-uniform lognormal radionuclide uptake.