A novel [(89)Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer

BACKGROUND: Harnessing the anti-tumor immune system response by targeting the program cell death protein (PD-1) and program cell death ligand protein (PD-L1) axis has been a major breakthrough in non-small cell lung cancer (NSCLC) therapy. Nonetheless, conventional imaging tools cannot accurately assess response in immunotherapy-treated patients. Using a lung cancer syngeneic mouse model responder to immunotherapy, we aimed to demonstrate that [(89)Zr]-anti-PD-1 immuno-PET is a safe and feasible imaging modality to assess the response to PD-1/PD-L1 blockade in NSCLC. MATERIALS AND METHODS: A syngeneic mouse model responder to anti-PD-1 therapy was used. Tumor growth and response to PD-1 blockade were monitored by conventional 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]-FDG) PET scans. Additionally, tumor lymphocyte infiltration was analyzed by the use of an [(89)Zr]-labeled anti-PD-1 antibody and measured as (89)Zr tumor uptake. RESULTS: Conventional [(18)F]-FDG-PET scans failed to detect the antitumor activity exerted by anti-PD-1 therapy. However, [(89)Zr]-anti-PD-1 uptake was substantially higher in mice that responded to PD-1 blockade. The analysis of tumor-infiltrating immune cell populations and interleukins demonstrated an increased anti-tumor effect elicited by activation of effector immune cells in PD-1-responder mice. Interestingly, a positive correlation between [(89)Zr]-anti-PD-1 uptake and the proportion of tumor-infiltrating lymphocytes (TILs) was found (Cor = 0.8; p = 0.001). CONCLUSION: Our data may support the clinical implementation of immuno-PET as a promising novel imaging tool to predict and assess the response of PD-1/PD-L1 inhibitors in patients with NSCLC.