PT  - JOURNAL ARTICLE
AU  - Stutvoet, Thijs S.
AU  - van der Veen, Elly L.
AU  - Kol, Arjan
AU  - Antunes, Inês F.
AU  - de Vries, Erik F.J.
AU  - Hospers, Geke A.P.
AU  - de Vries, Elisabeth G.E.
AU  - de Jong, Steven
AU  - Lub-de Hooge, Marjolijn N.
TI  - Molecular Imaging of PD-L1 Expression and Dynamics with the Adnectin-Based PET Tracer <sup>18</sup>F-BMS-986192
AID  - 10.2967/jnumed.119.241364
DP  - 2020 Dec 01
TA  - Journal of Nuclear Medicine
PG  - 1839--1844
VI  - 61
IP  - 12
4099  - http://jnm.snmjournals.org/content/61/12/1839.short
4100  - http://jnm.snmjournals.org/content/61/12/1839.full
SO  - J Nucl Med2020 Dec 01; 61
AB  - 18F-BMS-986192, an adnectin-based human programmed cell death ligand 1 (PD-L1) tracer, was developed to noninvasively determine whole-body PD-L1 expression by PET. We evaluated the usability of 18F-BMS-986192 PET to detect different PD-L1 expression levels and therapy-induced changes in PD-L1 expression in tumors. Methods: In vitro binding assays with 18F-BMS-986192 were performed on human tumor cell lines with different total cellular and membrane PD-L1 protein expression levels. Subsequently, PET imaging was performed on immunodeficient mice xenografted with these cell lines. The mice were treated with interferon γ (IFNγ) intraperitoneally for 3 d or with the mitogen-activated protein kinase kinase inhibitor selumetinib by oral gavage for 24 h. Afterward, 18F-BMS-986192 was administered intravenously, followed by a 60-min dynamic PET scan. Tracer uptake was expressed as percentage injected dose per gram of tissue. Tissues were collected to evaluate ex vivo tracer biodistribution and to perform flow cytometric, Western blot, and immunohistochemical tumor analyses. Results: 18F-BMS-986192 uptake reflected PD-L1 membrane levels in tumor cell lines, and tumor tracer uptake in mice was associated with PD-L1 expression measured immunohistochemically. In vitro IFNγ treatment increased PD-L1 expression in the tumor cell lines and caused up to a 12-fold increase in tracer binding. In vivo, IFNγ affected neither PD-L1 tumor expression measured immunohistochemically nor 18F-BMS-986192 tumor uptake. In vitro, selumetinib downregulated cellular and membrane levels of PD-L1 in tumor cells by 50% as measured by Western blotting and flow cytometry. In mice, selumetinib lowered cellular, but not membrane, PD-L1 levels of tumors, and consequently, no treatment-induced change in 18F-BMS-986192 tumor uptake was observed. Conclusion: 18F-BMS-986192 PET imaging allows detection of membrane-expressed PD-L1 as soon as 60 min after tracer injection. The tracer can discriminate a range of tumor cell PD-L1 membrane expression levels.