⁸⁹Zr-immuno-PET for imaging of long circulating drugs and disease targets: Why, how and when to be applied?

Positron emission tomography (PET) with ⁸⁹Zr-labeled monoclonal antibodies (mAbs) or other targeted vehicles {e.g., peptides, nanoparticles and cells), collectively called "⁸⁹Zr-immuno-PET", can be used for better understanding of disease targets and the in vivo behavior of targeted drugs. This will become increasingly important in the development of next generation mAbs, which are characterized by high potency and/or multiple binding domains. This review provides practical information for researchers who want to implement ⁸⁹Zr-immuno-PET for answering their own biological and pathological questions or for steering their own drug development program. An overview is given of the reagents, labeling protocols, quality tests and critical steps to come to high quality ⁸⁹Zr-conjugates, while possibilities for further improvement are discussed. Since PET has the advantage of allowing quantitative imaging, information is provided about standardization of ⁸⁹Zr quantification. Issues are summarized for consideration when starting preclinical or clinical ⁸⁹Zr-immuno-PET studies, to enable at the end unequivocal interpretation of results. Finally, many appealing examples are provided of what can be learned from ⁸⁹Zr-immuno-PET studies, while future directions are outlined. Most of the current examples are still on the characterization of mAbs in oncology, but the review will show that ⁸⁹Zr-immuno-PET harbors potential for many kinds of targeted drugs and diseases, as well as for elucidating biological processes.