75 PD-1/PD-L1 PET imaging: A novel tool to optimize immunotherapy? Table 2. Ongoing and awaited Clinical PD-1/PD-L1 imaging studies. Updated from original publication Clinical trial Phase Imaging technique Tumor type Patients 2015-004760-11 Completed [18F]F-PD-L1 and [89Zr]Zr-nivolumab PET/CT NSCLC n=10 NCT02453984 Completed [89Zr]Zr-atezolizumab PET/CT Locally advanced or metastatic solid tumors n=22 NCT03514719 (PINNACLE) Completed [89Zr]Zr-avelumab PET/CT NSCLC n=24 NCT03829007 (PINCH) Completed [89Zr]Zr-durvalumab and [18F]FDG PET/CT SCCHN n=58 2015-005765-23 Completed [89Zr]Zr-durvalumab PET/CT NSCLC n=10 NCT03520634 Completed [18F]F-PD-L1 PET/CT Melanoma n=15 NCT02760225 Completed [89Zr]Zr-pembrolizumab PET/CT Melanoma/NSCLC n=18 NCT03065764 Completed [89Zr]Zr-pembrolizumab PET/CT NSCLC n=10 NCT03843515 (NeoNivo) Active, not recruiting [18F]FDG PET and [18F]F-PD-L1 PET/CT Oral cavity squamous cell carcinoma n=15 NCT02978196 Unknown [99mTc]Tc-anti PD-L1 (sdAb) SPECT NSCLC n=50 NCT03850028 Recruiting [89Zr]Zr-atezolizumab PET/CT DLBCL n=20 NCT03853187 (DONAN) Recruiting [89Zr]Zr-durvalumab PET/CT and [111In]In- CD8 T cell SPECT NSCLC n=20 Finally, knowledge of the (differences in) makeup of currently available antibodies targeting PD-1/PD-L1 is essential for correct interpretation of (variable) tracer uptake58. Especially the interaction between the Fc-region of the antibody with the Fc-gamma receptors (FcyRs) presenting immunoglobulin (Ig)G subtypes. Vivier and colleagues59 suggested that the binding of humanized IgG1 by FcyRI contributes to the uptake of radiolabeled immuno-conjugates in nontarget tissues during antibody-based PET/CT imaging. Based on their findings, the use of deglycosylated radiolabeled immuno-conjugates is proposed to decrease unwanted uptake in healthy organs, thereby optimizing the imaging quality and interpretation. 4
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