Wunderlich G, Wendisch M, Aurich D, Runge R, Freudenberg R, Kotzerke J
Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Carl Gustav Carus, Technische Universität, 01307 Dresden, Fetscherstr. 74, Germany.
Nuklearmedizin. 2012;51(5):179-85. doi: 10.3413/Nukmed-0450-11-12. Epub 2012 Apr 12.
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.
锝放射性药物在核医学中已得到广泛应用。除了其众所周知的伽马辐射外，（99m）锝每次衰变平均发射五个俄歇电子和内转换电子。这些低能量、高传能线密度（LET）发射的生物毒性是一个有争议的话题。本研究的一个目的是在细胞模型中估计暴露细胞中可存在多少（99m）锝，以及在（99m）锝过载细胞中可估计出哪些放射生物学效应。
使用钠碘同向转运体（NIS）阳性的甲状腺细胞。在用非放射性（冷）焦磷酸亚锡试剂盒溶液预孵育后，或作为标准的（99m）锝焦磷酸试剂盒制剂，或用纯高锝酸盐溶液进行（99m）锝摄取研究。通过集落形成试验分析存活曲线。
用亚锡络合物预孵育会导致（99m）锝在细胞内不可逆地保留放射性，随后高锝酸盐进一步流入，达到意想不到的高（99m）锝水平。使用焦磷酸亚锡可将NIS阳性细胞中高锝酸盐的摄取从3 - 5%改变至>80%。（99m）锝的最大可能细胞摄取量为90Bq/细胞。与常规（99m）锝络合物几乎纯粹的细胞外照射相比，用焦磷酸亚锡预孵育后细胞存活率降低了3 - 4个数量级。
细胞内（99m）锝保留与存活率降低有关，这很可能是由低能电子发射介导的。我们的研究结果表明，所描述的实验构成了一个简单且有用的体外细胞模型放射生物学研究模型。
