Amsterdam UMC, Vrije Universiteit Amsterdam, Radiology & Nuclear Medicine, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam 1081 HV, The Netherlands.
Bioconjug Chem. 2021 Jul 21;32(7):1315-1330. doi: 10.1021/acs.bioconjchem.1c00136. Epub 2021 May 11.
Inert and stable radiolabeling of monoclonal antibodies (mAb), antibody fragments, or antibody mimetics with radiometals is a prerequisite for immuno-PET. While radiolabeling is preferably fast, mild, efficient, and reproducible, especially when applied for human use in a current Good Manufacturing Practice compliant way, it is crucial that the obtained radioimmunoconjugate is stable and shows preserved immunoreactivity and behavior. Radiometals and chelators have extensively been evaluated to come to the most ideal radiometal-chelator pair for each type of antibody derivative. Although PET imaging of antibodies is a relatively recent tool, applications with Zr, Cu, and Ga have greatly increased in recent years, especially in the clinical setting, while other less common radionuclides such as Mn, Y, Ga, and Sc, but also F as in [F]AlF are emerging promising candidates for the radiolabeling of antibodies. This review presents a state of the art overview of the practical aspects of radiolabeling of antibodies, ranging from fast kinetic affibodies and nanobodies to slow kinetic intact mAbs. Herein, we focus on the most common approach which consists of first modification of the antibody with a chelator, and after eventual storage of the premodified molecule, radiolabeling as a second step. Other approaches are possible but have been excluded from this review. The review includes recent and representative examples from the literature highlighting which radiometal-chelator-antibody combinations are the most successful for application.
将单克隆抗体（mAb）、抗体片段或抗体模拟物与放射性金属进行惰性和稳定的放射性标记是免疫 PET 的前提。虽然放射性标记最好是快速、温和、高效且可重复，尤其是在以符合现行良好生产规范的方式应用于人类时，但获得的放射性免疫缀合物必须是稳定的，并保持其免疫原性和行为是至关重要的。放射性金属和螯合剂已经得到了广泛的评估，以找到最适合每种类型抗体衍生物的放射性金属-螯合剂对。尽管使用 Zr、Cu 和 Ga 的抗体 PET 成像相对较新，但近年来在临床环境中，Zr、Cu 和 Ga 的应用大大增加，而其他不太常见的放射性核素，如 Mn、Y、Ga 和 Sc，以及 [F]AlF 中的 F，也作为抗体的放射性标记的有前途的候选物出现。这篇综述介绍了抗体放射性标记的实际方面的最新进展，范围从快速动力学的 Affibodies 和 Nanobodies 到缓慢动力学的完整 mAb。在此，我们重点介绍最常见的方法，该方法首先用螯合剂修饰抗体，然后在预修饰分子的最终储存后，作为第二步进行放射性标记。其他方法是可能的，但已排除在本综述之外。该综述包括来自文献的最新和有代表性的例子，突出了哪些放射性金属-螯合剂-抗体组合最适合应用。
