Good practices for 89Zr radiopharmaceutical production and quality control

Abstract

Abstract Background 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 ( 89 Zr-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 89 Zr in both clinical and pre-clinical settings, there is an urgent need to acquire valuable recommendations and guidelines towards standardization of labeling procedures. Main body This review provides an overview of the key aspects of 89 Zr-radiochemistry and radiopharmaceuticals. Production of 89 Zr, 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 89 Zr-immuno-PET, coordination chemistry of 89 Zr, and future perspectives are provided. This review aims to serve as a quick-start guide for scientists new to the field of 89 Zr-immuno-PET and to suggest approaches for harmonization and standardization of current procedures. Conclusion The favorable PET imaging characteristics of 89 Zr, 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 89 Zr. The combination of antibodies and 89 Zr, known as 89 Zr-immuno-PET, has become a cornerstone in drug development and patient selection in recent years. Despite the advanced state of 89 Zr-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.

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