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

Abstract

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 [⁸⁹Zr]-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-[¹⁸F]fluoro-D-glucose ([¹⁸F]-FDG) PET scans. Additionally, tumor lymphocyte infiltration was analyzed by the use of an [⁸⁹Zr]-labeled anti-PD-1 antibody and measured as ⁸⁹Zr tumor uptake.

Results: Conventional [¹⁸F]-FDG-PET scans failed to detect the antitumor activity exerted by anti-PD-1 therapy. However, [⁸⁹Zr]-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 [⁸⁹Zr]-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.

Keywords: PD-1 inhibition; immuno-PET; inhibitor of differentiation 1; lung adenocarcinoma; pseudoprogression.