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Imaging PD-L1 Expression with ImmunoPET.

  • Author(s): Truillet, Charles;
  • Oh, Hsueh Ling J;
  • Yeo, Siok Ping;
  • Lee, Chia-Yin;
  • Huynh, Loc T;
  • Wei, Junnian;
  • Parker, Matthew FL;
  • Blakely, Collin;
  • Sevillano, Natalia;
  • Wang, Yung-Hua;
  • Shen, Yuqin S;
  • Olivas, Victor;
  • Jami, Khaled M;
  • Moroz, Anna;
  • Jego, Benoit;
  • Jaumain, Emilie;
  • Fong, Lawrence;
  • Craik, Charles S;
  • Chang, Albert J;
  • Bivona, Trever G;
  • Wang, Cheng-I;
  • Evans, Michael J
  • et al.
Abstract

High sensitivity imaging tools could provide a more holistic view of target antigen expression to improve the identification of patients who might benefit from cancer immunotherapy. We developed for immunoPET a novel recombinant human IgG1 (termed C4) that potently binds an extracellular epitope on human and mouse PD-L1 and radiolabeled the antibody with zirconium-89. Small animal PET/CT studies showed that 89Zr-C4 detected antigen levels on a patient derived xenograft (PDX) established from a non-small-cell lung cancer (NSCLC) patient before an 8-month response to anti-PD-1 and anti-CTLA4 therapy. Importantly, the concentration of antigen is beneath the detection limit of previously developed anti-PD-L1 radiotracers, including radiolabeled atezolizumab. We also show that 89Zr-C4 can specifically detect antigen in human NSCLC and prostate cancer models endogenously expressing a broad range of PD-L1. 89Zr-C4 detects mouse PD-L1 expression changes in immunocompetent mice, suggesting that endogenous PD-1/2 will not confound human imaging. Lastly, we found that 89Zr-C4 could detect acute changes in tumor expression of PD-L1 due to standard of care chemotherapies. In summary, we present evidence that low levels of PD-L1 in clinically relevant cancer models can be imaged with immunoPET using a novel recombinant human antibody.

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