Imaging PD-L1 Expression with ImmunoPET

• Published in: Bioconjugate chemistry Vol. 29; no. 1; pp. 96 - 103
• Main Authors: Truillet, Charles, Oh, Hsueh Ling J, Yeo, Siok Ping, Lee, Chia-Yin, Huynh, Loc T, Wei, Junnian, Parker, Matthew F. L, 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
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17-01-2018
• Subjects: Animal models; Animals; Antigens; B7-H1 Antigen - analysis; Cancer; Cancer immunotherapy; Carcinoma, Non-Small-Cell Lung - diagnostic imaging; Cell Line, Tumor; Change detection; Computed tomography; CTLA-4 protein; Epitopes; HEK293 Cells; Humans; Imaging; Immunoconjugates - chemistry; Immunoglobulin G; Immunoglobulin G - chemistry; Immunotherapy; Lung - diagnostic imaging; Lung cancer; Lung Neoplasms - diagnostic imaging; Male; Mice; Mice, Inbred C57BL; Monoclonal antibodies; Non-small cell lung carcinoma; PD-1 protein; PD-L1 protein; Positron emission; Positron Emission Tomography Computed Tomography - methods; Prostate cancer; Radioisotopes - chemistry; Recombinant Proteins - chemistry; Targeted cancer therapy; Tomography; Xenografts; Xenotransplantation; Zirconium; Zirconium - chemistry; Zirconium isotopes
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/acs.bioconjchem.7b00631

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.