Molecular imaging on the move: From feasibility to contribution in clinical questions

Drug development, including agents targeting the immune system, have improved patient survival in multiple cancer types. Despite all achievements, however, cancer remains a leading cause of death worldwide. Resistance, inherent or developed, and tumor heterogeneity are possible causes for treatment failure. Obtaining detailed information on drugs, like whole body distribution and early response prediction are major challenges in clinical research.
In this thesis, we assess the role of molecular positron emission tomography (PET) imaging with radiolabeled antibodies as tool to obtain such knowledge. We describe and compare the whole body distribution of several antibodies, which are in clinical development or approved drugs for patient use. We describe that target saturation could be assessed by means of anti-human epidermal growth factor receptor 3 (HER3) antibody PET, that anti-programmed death ligand 1 (PD-L1) antibody PET predicted response to a PD-L1 targeting antibody more accurately than immunohistochemistry and RNA analysis, and that anti-HER2 antibody PET actually supported clinical decision making. Compared with conventional techniques, antibody PET can add dynamic whole body information, which may be of relevance particularly regarding the immune response.