Zirconium-89 labeled antibodies: general considerations towards radioisotope production and labelling strategies

Abstract

Radiopharmaceutical zirconium-89 (89Zr) radioisotope in the last decade have been increasingly used in preclinical and clinical studies for visualisation by positron emission tomography (PET). There are literature data on 89Zr labelling of nanoparticles, proteins, peptides and cells, but antibody labelling is the main application of this radioisotope. As a long-lived radiometal, with a half-life of 78.4 h, zirconium-89 is suitable for visualising slow biological processes, such as antibody biodistribution (immuno-PET). 89Zr-immunoPET imaging is a promising technique for predicting the efficacy of radioimmunotherapy and antibody therapies, imaging target expression, detecting target-expressing tumours, and monitoring anti-cancer chemotherapies. According to ClinicalTrials.gov, there are more than 120 clinical studies, of which already completed studies involve more than 20 antibodies labelled with 89Zr. The most common antibodies used in these clinical trials are bevacizumab, trastuzumab, IAB2M, cetuximab, pembrolizumab, J591, panitumumab, girentuximab, pertuzumab etc. The purpose of this paper is to present the most common methods of producing zirconium-89 radioisotope and antibody labelling strategies.