Immuno-PET imaging of Ga-68-labeled nanobody Nb109 for dynamic monitoring the PD-L1 expression in cancers
- 31 May 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cancer Immunology, Immunotherapy
- Vol. 70 (6), 1721-1733
- https://doi.org/10.1007/s00262-020-02818-y
Abstract
The checkpoint blockade immunotherapy has become a potent treatment strategy for cancers, and programmed death ligand-1 (PD-L1) is a prominent checkpoint ligand that is highly expressed in some cancers. The identification of immune checkpoint marker PD-L1 is critical for improving the success of immunotherapy. Accordingly, the binding specificity and dynamic monitoring property of a non-blocking nanobody tracer Ga-68-NOTA-Nb109 to PD-L1 were assessed in this study. The endogenous expression level of PD-L1 in several cancer cells was measured by flow cytometry, Western blot, and cellular uptake assay. Sensitivity and specificity of Ga-68-NOTA-Nb109 in monitoring the expression of PD-L1 in vivo were evaluated by PET imaging of different tumor-bearing models (U87, high PD-L1 expression; HCT 116, medium PD-L1 expression; and NCI-H1299, low PD-L1 expression). In vivo PET imaging results agreed well with those detected in vitro. In addition, PET imaging of PD-L1 expression in U87 and NCI-H1299 xenografts using F-18-FDG was also performed for comparison. The maximum tumor-to-muscle uptake ratio of Ga-68-NOTA-Nb109 was more than twofold that of F-18-FDG in U87 xenograft. The change of PD-L1 expression in NCI-H1299 cells and xenografts induced by cisplatin (CDDP) was sensitively monitored by Ga-68-NOTA-Nb109. This study demonstrated the feasibility of tracer Ga-68-NOTA-Nb109 for specifically targeting endogenous PD-L1 and dynamic monitoring the change of PD-L1 expression, and could guide the immunotherapy and immunochemotherapy for refractory cancers.Funding Information
- National Natural Science Foundation of China (81972906, 81971645, 22076069)
- Key Youth Medical Talent Project of Jiangsu Province (QNRC2016626, QNRC2016629)
- Precision Medical Project of Wuxi Commission of Health and Family Planning (J201806)
- Innovation Capacity Development Plan of Jiangsu Province (BM2018023)
- Natural Science Foundation of Jiangsu Province (BK20181128, BK20201135)
- Major Scientific Research Project of Wuxi Commission of Health (Z201913)
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