Preincubation with Sn-complexes causes intensive intracellular retention of 99mTc in thyroid cells in vitro

Abstract

Technetium radiopharmaceuticals are well established in nuclear medicine. Besides its well-known gamma radiation, (99m)Tc emits an average of five Auger and internal conversion electrons per decay. The biological toxicity of these low-energy, high-LET (linear energy transfer) emissions is a controversial subject. One aim of this study was to estimate in a cell model how much (99m)Tc can be present in exposed cells and which radiobiological effects could be estimated in (99m)Tc-overloaded cells. Sodium iodine symporter (NIS)-positive thyroid cells were used. (99m)Tc-uptake studies were performed after preincubation with a non-radioactive (cold) stannous pyrophosphate kit solution or as a standard (99m)Tc pyrophosphate kit preparation or with pure pertechnetate solution. Survival curves were analyzed from colony-forming assays. Preincubation with stannous complexes causes irreversible intracellular radioactivity retention of (99m)Tc and is followed by further pertechnetate influx to an unexpectedly high (99m)Tc level. The uptake of (99m)Tc pertechnetate in NIS-positive cells can be modified using stannous pyrophosphate from 3-5% to >80%. The maximum possible cellular uptake of (99m)Tc was 90Bq/cell. Compared with nearly pure extracellular irradiation from routine (99m)Tc complexes, cell survival was reduced by 3-4 orders of magnitude after preincubation with stannous pyrophosphate. Intracellular (99m)Tc retention is related to reduced survival, which is most likely mediated by the emission of low-energy electrons. Our findings show that the described experiments constitute a simple and useful in vitro model for radiobiological investigations in a cell model.