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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., (© 2024. The Author(s).)

Background: Nuclear medicine has made enormous progress in the past decades. However, there are still significant inequalities in patient access among different countries, which could be mitigated by improving access to and availability of radiopharmaceuticals., Main Body: This paper summarises major considerations for a suitable pharmaceutical regulatory framework to facilitate patient access to radiopharmaceuticals. These include the distinct characteristics of radiopharmaceuticals which require dedicated regulations, considering the impact of the variable complexity of radiopharmaceutical preparation, personnel requirements, manufacturing practices and quality assurance, regulatory authority interfaces, communication and training, as well as marketing authorisation procedures to ensure availability of radiopharmaceuticals. Finally, domestic and regional supply to ensure patient access via alternative regulatory pathways, including in-house production of radiopharmaceuticals, is described, and an outlook on regulatory challenges faced by new developments, such as the use of alpha emitters, is provided., Conclusions: All these considerations are an outcome of a dedicated Technical Meeting organised by the IAEA in 2023 and represent the views and opinions of experts in the field, not those of any regulatory authorities., (© 2023. The Author(s).)