⁸⁹Zr-radiopharmaceuticals to study whole-body distribution and response to antibody-based cancer immunotherapies

Immunotherapy has improved the survival of patients with advanced stages of various cancers, however, not all patients respond. Clinicians could benefit from increased knowledge about the pharmacokinetics of new immunotherapeutic drugs and factors that play a role in the development of a tumor response. The aim of the studies described in this thesis is to investigate whether molecular imaging with positron emission tomography (PET) can support this in two ways, namely 1) in the development of new drugs and 2) in optimizing treatment with immunotherapy. By radiolabeling an immunotherapeutic drug with a suitable isotope, such as zirconium-89 (89Zr), tumor uptake and whole-body distribution can be non-invasively imaged. In this thesis, we describe the development of several 89Zr-labeled antibodies, also called 89Zr radiopharmaceuticals. We demonstrate how PET imaging with these 89Zr-radiopharmaceuticals can provide insight into the pharmacokinetics of various immunotherapeutic antibodies that are still in (clinical) development or have already been approved for treatment of patients with certain cancers. We also show in a limited number of patients that tumor response to treatment with immune checkpoint inhibitors may be predicted by tumor uptake on the 89Zr-PET scan. In the future, PET imaging with 89Zr-radiopharmaceuticals could support the selection of patients who potentially benefit from immunotherapy treatment, and thereby clinical decision-making