Imaging PD-L1 expression with immunoPET.
High sensitivity imaging tools could provide a more holistic view of target antigen expression to improve the prospective identification of patients who might benefit from cancer immunotherapy. We developed for immunoPET a novel recombinant human IgG (termed C4) that potently binds an extracellular epitope on human and mouse PD-L1 and radiolabeled the antibody with zirconium-89. Small animal PET 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, this concentration is beneath the detection limit of previously developed anti-PD-L1 radiotracers. We also show that 89Zr-C4 can specifically detect its 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 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 show evidence that low levels of PD-L1 can imaged with immunoPET using a novel human antibody.