89 Zr-Labeled Anti-PD-L1 Antibody Fragment for Evaluating In Vivo PD-L1 Levels in Melanoma Mouse Model.

Autor:	Bridgwater C; Department of Radiology, University of Louisville, Louisville, Kentucky, USA., Geller A; Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA., Hu X; James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA., Burlison JA; James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA., Zhang HG; Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.; James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA., Yan J; Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.; James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.; Department of Surgery, University of Louisville, Louisville, Kentucky, USA., Guo H; Department of Radiology, University of Louisville, Louisville, Kentucky, USA.; Center for Predictive Medicine, University of Louisville, Louisville, Kentucky, USA.
Jazyk:	angličtina
Zdroj:	Cancer biotherapy & radiopharmaceuticals [Cancer Biother Radiopharm] 2020 Oct; Vol. 35 (8), pp. 549-557. Date of Electronic Publication: 2020 Apr 21.
DOI:	10.1089/cbr.2019.3056
Abstrakt:	The rise of programmed death-1 (PD-1)/PD-L1 immune checkpoint inhibitor therapy has been one of the most promising developments in melanoma research. However, not all the melanoma patients respond to such immune checkpoint blockade. There is a great need of biomarkers for appropriate melanoma patient selection and therapeutic efficacy monitoring. The objective of this study is to develop a novel radiolabeled anti-PD-L1 antibody fragment, as an imaging biomarker, for evaluating the in vivo PD-L1 levels in melanoma. The Df-conjugated F(ab') 2 fragment of the anti-mouse PD-L1 antibody was successfully synthesized and radiolabeled with 89 Zr. Both Df-F(ab') 2 and 89 Zr-Df-F(ab') 2 maintained the nano-molar murine PD-L1 targeting specificity and affinity. 89 Zr-Df-F(ab') 2 showed less uptake in normal liver tissue in mice compared with its full antibody counterpart 89 Zr-Df-anti-PD-L1. Positron emission tomography (PET)/computed tomography images clearly showed that 89 Zr-Df-F(ab') 2 possessed superior pharmacokinetics and imaging contrast over the radiolabeled full antibody, with much earlier and higher tumor uptake (5.5 times more at 2 h post injection) and much lower liver background (51% reduction at 2 h post injection). The specific and high murine PD-L1-targeting uptake at tumor foci coupled with fast clearance of 89 Zr-Df-F(ab') 2 highlighted its potential for in vivo PET imaging of murine PD-L1 levels and future development of radiolabeled anti-human PD-L1 fragment for potential application in melanoma patients.
Databáze:	MEDLINE
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