Direct radiolabeling of monoclonal antibodies with generator-produced rhenium-188 for radioimmunotherapy: labeling and animal biodistribution studies.
Direct radiolabeling of monoclonal antibodies with generator-produced rhenium-188 for radioimmunotherapy: labeling and animal biodistribution studies.
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发表时间：
1991-09
期刊：
影响因子：
11.2
通讯作者：
Gary L. Griffiths;David M. Goldenberg;F. F. Knapp-F.;Alvin P. Callahan;Chien‐Hsing Chang;Hans J. Hansen
中科院分区：
文献类型：
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作者：
Gary L. Griffiths;David M. Goldenberg;F. F. Knapp-F.;Alvin P. Callahan;Chien‐Hsing Chang;Hans J. Hansen
已研究了来自氧化铝基188 W/188 Re发生器的188 Re用于抗体放射性标记。结果发现，利用简单的标记技术，188 Re可以在洗脱后立即使用。完整的抗体与188 Re的直接放射性标记。冻干的抗体制剂用直接从发生器中取出的188 Re复溶，比活度高达15 mCi/mg抗体。已获得90 - 98%的放射性标记产率，掺入率取决于时间和试剂的相对浓度。它被确定为共轭物是免疫反应性和稳定的挑战时，血清在体外，与188 Re-免疫球蛋白G显示出足够的抗再氧化与188 Re没有转移到血清蛋白。188 Re-抗体结合物显示出比相应的131 I-标记抗体更快地从血液中清除，在注射后24至72小时产生良好的肿瘤/非肿瘤比率，而从动物采集的血清样品显示循环的188 Re仍然与免疫球蛋白G结合。188 W/188 Re发生器、直接标记方法和使用单瓶冻干抗体的技术的组合使得使用188 Re放射性标记的单克隆抗体成为使用β发射放射性核素进行癌症放射免疫治疗的简单和方便的方法。
The use of 188Re from an alumina-based 188W/188Re generator has been investigated for antibody radiolabeling. It was found that, with simple labeling techniques, 188Re can be used immediately after elution. The direct radiolabeling of intact antibodies with 188Re is described. Lyophilized antibody preparations have been reconstituted with 188Re taken directly from the generator at specific activities of up to 15 mCi of 188Re per mg of antibody. Radiolabeling yields of 90 to 98% have been obtained, with the incorporation rate being dependent upon time and the relative concentrations of the reagents. It was determined that the conjugates were immunoreactive and stable when challenged by serum in vitro, with 188Re-immunoglobulin G showing adequate resistance to reoxidation with no transfer of 188Re to serum protein. 188Re-antibody conjugates were shown to clear from the blood faster than the corresponding 131I-labeled antibody, giving rise to good tumor/nontumor ratios at 24 to 72 h postinjection, while serum samples taken from the animals have shown that the circulating 188Re remained bound to immunoglobulin G. The combination of the technologies of the 188W/188Re generator, the direct labeling methodology, and the use of single-vial lyophilized antibody makes the use of 188Re-radiolabeled monoclonal antibodies a simple and convenient method of cancer radioimmunotherapy with a beta-emitting radionuclide.