Centre for Cancer Research and Cell Biology, Queen's University Belfast , Belfast , UK.
Front Oncol. 2013 Aug 19;3:215. doi: 10.3389/fonc.2013.00215. eCollection 2013.
Radionuclide therapy for cancer is undergoing a renaissance, with a wide range of radionuclide and clinical delivery systems currently under investigation. Dosimetry at the cellular and sub-cellular level is complex with inhomogeneity and incomplete targeting of all cells such that some tumor cells will receive little or no direct radiation energy. There is now sufficient preclinical evidence of a Bystander response which can modulate the biology of these un-irradiated cells with current research demonstrating both protective and inhibitory responses. Dependence upon fraction of irradiated cells has also been found and the presence of functional gap junctions appears to be import for several Bystander responses. The selection of either high or low LET radionuclides may be critical. While low LET radionuclides appear to have a Bystander response proportional to dose, the dose-response from high LET radionuclides are more complex. In media transfer experiments a "U" shaped response curve has been demonstrated for high LET treatments. However this "U" shaped response has not been seen with co-culture experiments and its relevance remains uncertain. For high LET treatments there is a suggestion that dose rate effects may also be important with inhibitory effects noted with 125I labelling study and a stimulatory seen with 123I labelling in one study.
癌症的放射性核素治疗正在复兴，目前有广泛的放射性核素和临床输送系统正在研究中。细胞和亚细胞水平的剂量学是复杂的，存在不均匀性和所有细胞的不完全靶向，因此一些肿瘤细胞将很少或根本不会直接受到辐射能的影响。现在有足够的临床前证据表明旁观者反应可以调节这些未受照射细胞的生物学特性，目前的研究表明存在保护和抑制反应。还发现了对受照射细胞分数的依赖性，并且功能性间隙连接的存在似乎对几种旁观者反应很重要。选择高或低 LET 放射性核素可能是关键。虽然低 LET 放射性核素似乎具有与剂量成比例的旁观者反应，但高 LET 放射性核素的剂量反应更为复杂。在介质转移实验中，已经证明了高 LET 治疗的“U”形反应曲线。然而，在共培养实验中没有看到这种“U”形反应，其相关性仍然不确定。对于高 LET 治疗，有人认为剂量率效应也可能很重要，在 125I 标记研究中观察到抑制作用，在一项研究中观察到 123I 标记的刺激作用。
