Imaging PD-L1 Expression with ImmunoPET

Bioconjug Chem. 2018 Jan 17;29(1):96-103. doi: 10.1021/acs.bioconjchem.7b00631. Epub 2017 Nov 15.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen / analysis*
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging*
  • Cell Line, Tumor
  • HEK293 Cells
  • Humans
  • Immunoconjugates / chemistry*
  • Immunoglobulin G / chemistry*
  • Lung / diagnostic imaging
  • Lung Neoplasms / diagnostic imaging*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Positron Emission Tomography Computed Tomography / methods*
  • Radioisotopes / chemistry*
  • Recombinant Proteins / chemistry
  • Zirconium / chemistry*


  • B7-H1 Antigen
  • CD274 protein, human
  • Immunoconjugates
  • Immunoglobulin G
  • Radioisotopes
  • Recombinant Proteins
  • Zirconium
  • Zirconium-89