Imaging PD-L1 Expression with ImmunoPET
Year: 2017
Type: article
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.
Source: Bioconjugate Chemistry
Authors: Charles Truillet, Hsueh Ling J. Oh, Siok Ping Yeo, Chia-Yin Lee, Loc T. Huynh, Junnian Wei, Matthew F. L. Parker, Collin Blakely, Natalia Sevillano, Yung-Hua Wang, Yuqin S. Shen, Victor Olivas, Khaled M. Jami, Anna Moroz, Benoit Jego, Emilie Jaumain, Lawrence Fong, Charles S. Craik, Albert J. Chang, Trever G. Bivona, Cheng-I Wang, Michael J. Evans
Institutions: Université Paris-Sud, Centre National de la Recherche Scientifique, Inserm, University of California, San Francisco, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, CEA Paris-Saclay - Etablissement de Saclay, UCSF Helen Diller Family Comprehensive Cancer Center, Agency for Science, Technology and Research, Singapore Immunology Network, Skolkovo Institute of Science and Technology
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funders: U.S. Department of Defense, Pew Charitable Trusts, Prostate Cancer Foundation, Alexander and Margaret Stewart Trust, Agency for Science, Technology and Research, National Institutes of Health, GE Healthcare, University of California, San Francisco, Biomedical Research Council, National Cancer Institute, Academic Senate, University of California, Riverside, DOD Prostate Cancer Research Program
OpenAlex ID: W2767824485