PET imaging with ⁸⁹Zr: from radiochemistry to the clinic

The advent of antibody-based cancer therapeutics has led to the concomitant rise in the development of companion diagnostics for these therapies, particularly nuclear imaging agents. A number of radioisotopes have been employed for antibody-based PET and SPECT imaging, notably ⁶⁴Cu, ¹²⁴I, ¹¹¹In, and (99m)Tc; in recent years, however, the field has increasingly focused on ⁸⁹Zr, a radiometal with near ideal physical and chemical properties for immunoPET imaging. In the review at hand, we seek to provide a comprehensive portrait of the current state of ⁸⁹Zr radiochemical and imaging research, including work into the production and purification of the isotope, the synthesis of new chelators, the development of new bioconjugation strategies, the creation of novel ⁸⁹Zr-based agents for preclinical imaging studies, and the translation of ⁸⁹Zr-labeled radiopharmaceuticals to the clinic. Particular attention will also be dedicated to emerging trends in the field, ⁸⁹Zr-based imaging applications using vectors other than antibodies, the comparative advantages and limitations of ⁸⁹Zr-based imaging compared to that with other isotopes, and areas that would benefit from more extensive investigation. At bottom, it is hoped that this review will provide both the experienced investigator and new scientist with a full and critical overview of this exciting and fast-developing field.