Capala J, Pråhl M, Scott-Robson S, Pontén J, Westermark B, Carlsson J
Department of Radiation Sciences, Uppsala University, Sweden.
J Neurooncol. 1990 Dec;9(3):201-10. doi: 10.1007/BF02341150.
Malignant glioma cells often have more epidermal growth factor (EGF) receptors than normal cells and targeting of toxic substances to the receptor might therefore be an attractive therapeutical approach. Radiation effects were analysed on human glioma cells growing as monolayers after exposure to 131I-EGF. Unspecific effects were analysed with 131I-BSA or after presaturation with nonradioactive EGF. The radiation effects were compared to the effects obtained by external 60Co gamma irradiation. Administration of the highest radioactive concentrations, 0.2-0.5 MBq/ml in the culture medium, corresponded, after 20 min incubation, to a binding of about 1.0-2.5 dpm/cell. Such an exposure to 131I decays gave effects on cell survival corresponding to about 2.5 Gy of external gamma irradiation. Somewhat less than half of this effect came from the specific bound radioactivity and the rest from nonbound radioactivity. When administrating lower concentrations of radioactivity both the binding and the radiation effects were smaller. The observations showed that it is possible to inactivate cell-proliferation of glioma cells with specific bound 131I-EGF. The possibilities to fractionate the treatments and of binding also other toxic agents than 131I to the EGF receptor are discussed.
恶性胶质瘤细胞通常比正常细胞具有更多的表皮生长因子(EGF)受体,因此将有毒物质靶向该受体可能是一种有吸引力的治疗方法。在暴露于¹³¹I-EGF后,对单层生长的人胶质瘤细胞的辐射效应进行了分析。用¹³¹I-牛血清白蛋白(BSA)或在先用非放射性EGF预饱和后分析非特异性效应。将辐射效应与通过外部⁶⁰Coγ射线照射获得的效应进行比较。在培养基中给予最高放射性浓度0.2 - 0.5 MBq/ml,孵育20分钟后,相当于约1.0 - 2.5 dpm/细胞的结合量。这样暴露于¹³¹I衰变对细胞存活产生的效应相当于约2.5 Gy的外部γ射线照射。这种效应中略少于一半来自特异性结合的放射性,其余来自未结合的放射性。当给予较低浓度的放射性时,结合和辐射效应都较小。观察结果表明,用特异性结合的¹³¹I-EGF使胶质瘤细胞的细胞增殖失活是可能的。还讨论了分割治疗以及将¹³¹I以外的其他有毒剂与EGF受体结合的可能性。