89Zr-PET radiochemistry in the development and application of therapeutic monoclonal antibodies and other biologicals.
89Zr-PET radiochemistry in the development and application of therapeutic monoclonal antibodies and other biologicals.
复制标题
89Zr-PET放射化学在治疗性单克隆抗体和其他生物制品的开发和应用中的应用。
DOI：
10.2174/1568026611313040005
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发表时间：
2013
影响因子：
3.4
通讯作者：
G. V. van Dongen
中科院分区：
文献类型：
--
作者：
D. Vugts;G. Visser;G. V. van Dongen
正电子发射断层扫描与（89）锆可用于跟踪治疗性单克隆抗体（mAb）和其他生物制剂在体内的行为。（89）Zr的有利放射物理特性允许在注射后进行多天PET扫描。对于（89）Zr与蛋白质的偶联，已经描述了六种基于去铁胺（DFO）的双功能螯合剂，其中五种在体内形成稳定的络合物。在得到稳定复合物的方法中，三种是基于mAb的随机赖氨酸修饰，两种是基于位点特异性工程。到目前为止，只有两种方法，随机赖氨酸修饰N-Bz-DFO或DFO-Bz-NCS，已用于临床研究。在这篇综述中，首先强调（89）Zr的物理化学性质和生产方面，以及必须考虑的重要项目，以符合当前良好的生产规范（cGMP）的（89）Zr标记的蛋白质的生产。接下来，将讨论不同的基于DFO的缀合策略的合成，以及它们的（预）临床评价，特别是在肿瘤学领域。
Positron emission tomography with (89)Zr can be used to follow the behaviour of therapeutic monoclonal antibodies (mAbs) and other biologicals in vivo. The favourable radiophysical characteristics of (89)Zr allow multiple days PET scanning after injection. For the coupling of (89)Zr to proteins six desferrioxamine (DFO)-based bifunctional chelators have been described, five of which forming stable complexes in vivo. Of the methods that give stable complexes three are based on random lysine modification of mAbs and two on site-specific engineering. Up to now only two methods, random lysine modification with N-suc-DFO or DFO-Bz-NCS, have been used in clinical studies. In this review firstly aspects of the physicochemical properties and production of (89)Zr are emphasized as well as important items that have to be taken into account for current good manufacturing practice (cGMP) compliant production of (89)Zr-labeled proteins. Next, the different DFO-based conjugation strategies will be discussed with respect to synthesis, and their (pre)clinical evaluation particularly in the field of oncology.