During the previous two decades, PET imaging of biopharmaceuticals radiolabeled with zirconium-89 has become a consistent tool in preclinical and clinical drug development and patient selection, primarily due to its advantageous physical properties that allow straightforward radiolabeling of antibodies (89Zr-immuno-PET). The extended half-life of 78.4 h permits flexibility with respect to the logistics of tracer production, transportation, and imaging and allows imaging at later points in time. Additionally, its relatively low positron energy contributes to high-sensitivity, high-resolution PET imaging. Considering the growing interest in radiolabeling antibodies, antibody derivatives, and other compound classes with 89Zr in both clinical and pre-clinical settings, there is an urgent need to acquire valuable recommendations and guidelines towards standardization of labeling procedures. This review provides an overview of the key aspects of 89Zr-radiochemistry and radiopharmaceuticals. Production of 89Zr, conjugation with the mostly used chelators and radiolabeling strategies, and quality control of the radiolabeled products are described in detail, together with discussions about alternative options and critical steps, as well as recommendations for troubleshooting. Moreover, some historical background on 89Zr-immuno-PET, coordination chemistry of 89Zr, and future perspectives are provided. This review aims to serve as a quick-start guide for scientists new to the field of 89Zr-immuno-PET and to suggest approaches for harmonization and standardization of current procedures. The favorable PET imaging characteristics of 89Zr, its excellent availability due to relatively simple production and purification processes, and the development of suitable bifunctional chelators have led to the widespread use of 89Zr. The combination of antibodies and 89Zr, known as 89Zr-immuno-PET, has become a cornerstone in drug development and patient selection in recent years. Despite the advanced state of 89Zr-immuno-PET, new developments in chelator conjugation and radiolabeling procedures, application in novel compound classes, and improved PET scanner technology and quantification methods continue to reshape its landscape towards improving clinical outcomes.

中文翻译：

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89Zr放射性药物生产和质量控制良好实践

在过去的二十年中，锆 89 放射性标记生物药物的 PET 成像已成为临床前和临床药物开发以及患者选择的一致工具，这主要是由于其有利的物理特性，可以直接对抗体进行放射性标记（89Zr-免疫-PET） 。 78.4 小时的延长半衰期为示踪剂生产、运输和成像的物流提供了灵活性，并允许在以后的时间点进行成像。此外，其相对较低的正电子能量有助于高灵敏度、高分辨率 PET 成像。考虑到在临床和临床前环境中人们对放射性标记抗体、抗体衍生物和其他 89Zr 化合物类别的兴趣日益浓厚，迫切需要获得有关标记程序标准化的有价值的建议和指南。本综述概述了 89Zr 放射化学和放射性药物的关键方面。详细描述了 89Zr 的生产、与最常用的螯合剂和放射性标记策略的结合以及放射性标记产品的质量控制，并讨论了替代方案和关键步骤，以及故障排除建议。此外，还提供了 89Zr-immuno-PET 的一些历史背景、89Zr 的配位化学以及未来的展望。本综述旨在为刚接触 89Zr-immuno-PET 领域的科学家提供快速入门指南，并为当前程序的协调和标准化提出建议。 89Zr 良好的 PET 成像特性、相对简单的生产和纯化工艺带来的优异可用性以及合适的双功能螯合剂的开发导致了 89Zr 的广泛使用。抗体和89Zr的组合，被称为89Zr-immuno-PET，近年来已成为药物开发和患者选择的基石。尽管 89Zr-免疫-PET 处于先进状态，但螯合剂缀合和放射性标记程序的新发展、新型化合物类别的应用以及改进的 PET 扫描仪技术和定量方法继续重塑其前景，以改善临床结果。