Sarah Verhoeff

146 Chapter 8 To further optimize clinical use and steer treatment schedules of antibody therapeutics, we believe that experimental molecular imaging techniques (e.g., PD-L1 PET-imaging) will perhaps have more impact when implemented in early drug development. In earlier phase I-II clinical trials, it could be used as a tool to identify the optimal treatment dose, combination strategies or identify effector mechanisms or mechanisms of (acquired) resistance such as the upregulation of other checkpoint molecules. This knowledge should be obtained before multiple drugs directed against the same target receive approval for clinical use28. Molecular PET imaging to steer treatment for cancer patients? While [18F]FDG PET/CT has been implemented in daily clinical practice, experimental molecular PET imaging is not yet able to steer treatment of cancer patients. However, [18F]FDG PET/CT in mccRCC patients illustrates the potential of PET imaging to address inter-patient heterogeneity in underlying tumor biology with direct consequence for patient management. In contrast to routinely available [18F]FDG however, and based on our experiences, there are currently too many (practical) limitations that hamper the implementation of experimental PET-imaging such as PD-L1 PET imaging into clinical practice. Nevertheless, the in vivo visualization of monoclonal antibodies, as demonstrated in this thesis, has led to a more balanced discussion on the potential role of antibody-based imaging, especially with respect to prediction of ICI therapy response. We have provided insight on the in vivo biodistribution of therapeutic antibodies and clues to further enhance current approaches of molecular imaging. Once implemented in early drug development, this knowledge might contribute to the optimization of treatment efficacy. Therefore, the title of this thesis ‘molecular PET imaging to steer treatment for cancer patients’ remains our aim for the future.