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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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