The navigating and de-risking role of ⁸⁹Zr-immuno-PET in the development of biopharmaceuticals

Abstract

The identification of molecular drivers of disease and the compelling rise of biotherapeutics such as peptides, monoclonal antibodies, antibody fragments and non-traditional binding scaffolds, activatable antibodies, bispecific antibodies, immunocytokines, antibody drug conjugates, enzymes, polynucleotides, therapeutic cells as well as alternative drug carriers like nanoparticles have impacted clinical care but also came with challenges. Drug development is expensive, attrition rates are high, and efficacy rates are lower than desired. Nowadays almost all these drugs, that in general have a long residence time in the body, can be stably labeled with ⁸⁹Zr for whole body-PET imaging and quantification. Although not restricted to monoclonal antibodies, this approach is called ⁸⁹Zr-immuno-PET. This review summarizes at a high level the State of the Art of the technical aspects of ⁸⁹Zr-immuno-PET, and illustrates why it has potential for steering the design, development and application of biological drugs. Appealing showcases are discussed to illustrate what can be learned with this emerging technology during preclinical and especially clinical studies about biological drug formats and disease targets. In addition, an overview of ongoing and completed clinical trials is provided. Although ⁸⁹Zr-immuno-PET is a young tool in drug development, its application is rapidly expanding, with first clinical experiences giving insight why certain drug-target combinations might have better perspectives than others.