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

Imaging PD-L1 Expression with ImmunoPET.

Author information

1
Department of Radiology and Biomedical Imaging, ‡Department of Medicine, §Helen Diller Family Comprehensive Cancer Center, ∥Department of Pharmaceutical Chemistry, and ⊥Department of Radiation Oncology, University of California, San Francisco , 505 Parnassus Avenue, San Francisco, California 94143, United States.
2
Imagerie Moleculaire in Vivo, INSERM, CEA, Université Paris Sud, CNRS, Universite Paris Saclay, CEA-Service Hospitalier Frederic Joliot , Orsay 94100, France.
3
Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR) , 8A Biomedical Grove Immunos No. 03-06, Biopolis 138648, Singapore.
4
Skolkovo Institute of Science and Technology, Skolkovo Innovation Center , 3 Nobel Street, Moscow 143026, Russia.

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.

PMID:
29125731
PMCID:
PMC5773933
DOI:
10.1021/acs.bioconjchem.7b00631
[Indexed for MEDLINE]
Free PMC Article

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