Rapid PD-L1 detection in tumors with PET using a highly specific peptide

Samit Chatterjee , Wojciech G. Lesniak , Michelle S. Miller , Ala Lisok , Emilia Sikorska , Bryan Wharram , Dhiraj Kumar , Matthew Gabrielson , Martin G. Pomper , Sandra B. Gabelli , Sridhar Nimmagadda

Abstract

Molecular imaging can report on the status of the tumor immune microenvironment and guide immunotherapeutic strategies to enhance the efficacy of immune modulation therapies. Imaging agents that can rapidly report on targets of immunomodulatory therapies are few. The programmed death ligand 1 (PD-L1) is an immune checkpoint protein over-expressed in several cancers and contributes to tumor immune suppression. Tumor PD-L1 expression is indicative of tumor response to PD-1 and PD-L1 targeted therapies. Herein, we report a highly specific peptide-based positron emission tomography (PET) imaging agent for PD-L1. We assessed the binding modes of the peptide WL12 to PD-L1 by docking studies, developed a copper-64 labeled WL12 ([64Cu]WL12), and performed its evaluation in vitro, and in vivo by PET imaging, biodistribution and blocking studies. Our results show that [64Cu]WL12 can be used to detect tumor PD-L1 expression specifically and soon after injection of the radiotracer, to fit within the standard clinical workflow of imaging within 60 min of administration.
Author Samit Chatterjee
Samit Chatterjee,,
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, Wojciech G. Lesniak
Wojciech G. Lesniak,,
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, Michelle S. Miller
Michelle S. Miller,,
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, Ala Lisok
Ala Lisok,,
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, Emilia Sikorska PBSB
Emilia Sikorska,,
- Pracownia Badań Strukturalnych Biopolimerów
, Bryan Wharram
Bryan Wharram,,
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, Dhiraj Kumar
Dhiraj Kumar,,
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, Matthew Gabrielson
Matthew Gabrielson,,
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, Martin G. Pomper
Martin G. Pomper,,
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, Sandra B. Gabelli
Sandra B. Gabelli,,
-
et al.
Journal seriesBiochemical and Biophysical Research Communications, ISSN 0006-291X
Issue year2017
Vol483
No1
Pages258-263
Publication size in sheets0.5
Keywords in Englishimmunotherapy, immune checkpoint, diagnostics, peptides, PD-1
DOIDOI:10.1016/j.bbrc.2016.12.156
URL http://dx.doi.org/10.1016/j.bbrc.2016.12.156
Languageen angielski
Score (nominal)25
ScoreMinisterial score = 25.0, 20-12-2017, ArticleFromJournal
Ministerial score (2013-2016) = 25.0, 20-12-2017, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 2.466 (2) - 2016=2.354 (5)
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