89Zr-Labeled Anti-PD-L1 Antibody Fragment for Evaluating In Vivo PD-L1 Levels in Melanoma Mouse Model.
Cancer Biother Radiopharm
; 35(8): 549-557, 2020 Oct.
Article
em En
| MEDLINE
| ID: mdl-32315549
ABSTRACT
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 89Zr. Both Df-F(ab')2 and 89Zr-Df-F(ab')2 maintained the nano-molar murine PD-L1 targeting specificity and affinity. 89Zr-Df-F(ab')2 showed less uptake in normal liver tissue in mice compared with its full antibody counterpart 89Zr-Df-anti-PD-L1. Positron emission tomography (PET)/computed tomography images clearly showed that 89Zr-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 89Zr-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.
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MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Melanoma Experimental
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Imunoconjugados
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Antígeno B7-H1
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article