Zirconium immune-complexes for PET molecular imaging: Current status and prospects

Diagnostic molecular images, obtained by positron emission tomography (PET), have successfully functioned as sensitive tools for detecting and monitoring the treatment of different diseases, mainly cancer. However, cancer proteomics has shown that the expression of specific molecular targets is dynamic, transforming nuclear molecular imaging techniques from purely diagnostic to procedures aimed at the prognosis of the disease for precise treatment selection. Of all commercially available pure PET radionuclides, zirconium-89 is the only one with a sufficient half-life (t1/2 = 3.27 d) to be useful for the labeling of antibodies, antibody fragments, cells, and nanoparticles. Therefore, the routine use of 89Zr–immunoPET is expected to help determine the prognosis and benefit of immunotherapies in cancer patients, such as anti-FAP, anti-CD44, anti-VEGF, anti-EGFR, anti-TGF-b, anti-PSMA, anti-STEAP1, anti-HER2/3, and/or anti-PD-L1. For this purpose, stable coordination of zirconium to bifunctional chelators is essential to form efficient radioimmunoconjugates with molecular targeting capabilities, which, combined with high PET resolution and sensitivity, could offer the most advanced tool for cancer prognosis, treatment definition and follow-up. In this manuscript, recent achievements concerning the coordination chemistry of zirconium (IV) to different chelators, the different molecular targets identified using immunoPET, the drug delivery systems based on 89Zr-antibody-drug conjugates/nanoparticles, and cell tracking with 89Zr, are reviewed and discussed.