Abstract
BACKGROUND: Immuno-positron emission tomography (immuno-PET) imaging is emerging as a highly promising technique for the non-invasive diagnosis of a wide range of pathological conditions, particularly in oncology and immunology. This molecular imaging modality enables the visualization, characterization, and quantification of biological processes at a cellular and molecular level. MAIN BODY: Immuno-PET relies mostly on the administration of monoclonal antibodies (mAb) labeled with positron-emitting radionuclides. These antibodies are specifically designed to bind to antigens that are overexpressed on tumor cells or involved in pathological non-neoplastic processes, such as inflammatory or autoimmune diseases. Numerous disease-associated antigens have been identified and are currently being explored as potential molecular targets for immuno-PET, paving the way for more personalized diagnostic and treatment approaches. This technique offers significant potential in the context of theranostic, as it allows for the simultaneous assessment of both diagnostic and therapeutic parameters. It is particularly useful for predicting and monitoring the pharmacokinetics and biodistribution of targeted therapies, thereby helping to optimize therapeutic efficacy while minimizing adverse effects. Among the various radioisotopes available, zirconium-89 ((89)Zr) has gained attention as a particularly suitable candidate for mAb labeling due to its favorable physicochemical characteristics such as its half-life (78.4 h), which matches well with the slow kinetics of intact antibodies, and its appropriate positron emission profile for high-resolution imaging. Despite the growing interest in immuno-PET and the increasing number of radiolabeling protocols described in the literature, the clinical implementation of (89)Zr-labeled mAbs faces numerous challenges. These include logistical and technical hurdles, but more significantly, regulatory obstacles that vary across countries and between regulatory authorities, particularly within Europe. Such disparities hinder the harmonization of clinical trials and limit access to immuno-PET technologies for many research centers. CONCLUSION: In this review, we aim to provide an overview of the current clinical applications of (89)Zr-labeled mAbs, based on published studies and ongoing trials, and highlight the key challenges that need to be addressed to expand access to this powerful imaging modality.