134 Chapter 7 Clinical trial Imaging technique (PET) Tumor type Patients Results Bensch et al. 10 NCT02453984 [89Zr]Zr-atezolizumab Locally advanced or metastatic solid tumors n=22 • [89Zr]Zr-atezolizumab PET/CT is feasible and safe • [89Zr]Zr-atezolizumab uptake correlates to PD-L1 expression • [89Zr]Zr-atezolizumab SUVmax predicts response to atezolizumab including OS and PFS better than PD-L1 expression assessed by IHC Niemeijer et al. 11 2015-004760-11 [18F]F-PD-L1 [89Zr]Zr-nivolumab NSCLC n=13 • [18F]F-PD-L1 and [89Zr]Zrnivolumab PET is feasible and safe • [18F]F-PD-L1 uptake correlates to tumor PD-L1 expression • [89Zr]Zr-nivolumab uptake correlates to PD-L expression on lymphocytic aggregates • [89Zr]Zr-atezolizumab SUVpeak correlates to treatment response (responders vs non-responders based on RECIST 1.1) CONCLUSION We are back to our main question: should clinical PD-(L)-1 axis imaging be used as a predictive biomarker, for preselection of patients, or might another role better match the biomarkerprofile? We believe 89Zr-labeled ICI imaging can add value in better understanding clinical ICI responses, revealing ways of therapy resistance, and in future immuno-oncology drug selection and development. To achieve this, essential steps forward are: 1) obtaining histology for validation and in depth molecular- and immune cell profiling; 2) evaluation by whole-body PET/CT radiolabeled antibodies to dynamically approach immunological responses. Here, different uptake parameters may correlate with clinical response; 3) knowledge on antibody distribution, binding characteristics, and metabolic pathways should be gathered in a data warehouse to increase understanding of molecular imaging and support holistic multi-dimensional research16; and 4) ensuring prospective standardization based on international guidelines. Taken together, we believe radiolabeled ICI imaging is valuable in current and future mechanismdriven ICI studies to improve ICI treatment.
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