Radiopharmaceuticals for translational imaging studies in the field of cancer immunotherapy

Abstract

Cancer immunotherapy allows a relevant new treatment strategy for patients with cancer. Especially immune checkpoint inhibitors have shown remarkable anti-tumor effects. Although these treatments have shown to clearly affect outcome in various settings, major challenges are that not every patient responds to immune checkpoint inhibitor therapy and that this treatment can lead to serious side effects. Therefore, strategies are required to improve patient selection and predict response to these expensive immunotherapeutics. Molecular imaging, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), with specific radiopharmaceuticals can provide non-invasive whole body information about the biodistribution of immune checkpoint inhibitors in the body, heterogeneity of target expression, effects of immunotherapy on immune cells, and therapy effects on other cells in the tumor microenvironment. The aim of this thesis is to develop new radiopharmaceuticals for molecular imaging in the field of cancer immunotherapy. We show the challenging development and preclinical evaluation of radiolabeled immune checkpoint protein antibodies and small molecules. Furthermore, we describe their potential for immune cell imaging in preclinical studies. Additionally, we showed the feasibility of molecular imaging with a PD-L1 antibody in a small size clinical imaging trial. In the future, this approach might lead to better patient selection to improve therapy outcomes for cancer immunotherapy.