title: Rapid PD-L1 detection in tumors with PET using a highly specific peptide.
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.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Samit
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Wojciech G
authors.initials: WG
authors.lastname: Lesniak
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Miller
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Ala
authors.initials: A
authors.lastname: Lisok
authors.affiliation: Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308, Gdańsk, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Sikorska
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Wharram
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gabrielson
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore, MD, USA; Departments of Medicine and Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, Baltimore, MD, USA.
authors.forename: Sandra B
authors.initials: SB
authors.lastname: Gabelli
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA. Electronic address: snimmag1@jhmi.edu.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Nimmagadda
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000032:analysis* / Q000378:metabolism; D016466:CHO Cells; D003301:Copper Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D003412:Cricetulus; D064907:Diagnostic Uses of Chemicals; D005260:Female; D006801:Humans; D016513:Mice, SCID; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D003301:Copper Radioisotopes; D064907:Diagnostic Uses of Chemicals; C105992:PDCD1 protein, human; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor
keywords: Diagnostics; Immune checkpoint; Immunotherapy; PD-1; Peptides