AUTHOR=Leung David , Bonacorsi Samuel , Smith Ralph Adam , Weber Wolfgang , Hayes Wendy TITLE=Molecular Imaging and the PD-L1 Pathway: From Bench to Clinic JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.698425 DOI=10.3389/fonc.2021.698425 ISSN=2234-943X ABSTRACT=

Programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors target the important molecular interplay between PD-1 and PD-L1, a key pathway contributing to immune evasion in the tumor microenvironment (TME). Long-term clinical benefit has been observed in patients receiving PD-(L)1 inhibitors, alone and in combination with other treatments, across multiple tumor types. PD-L1 expression has been associated with response to immune checkpoint inhibitors, and treatment strategies are often guided by immunohistochemistry-based diagnostic tests assessing expression of PD-L1. However, challenges related to the implementation, interpretation, and clinical utility of PD-L1 diagnostic tests have led to an increasing number of preclinical and clinical studies exploring interrogation of the TME by real-time imaging of PD-(L)1 expression by positron emission tomography (PET). PET imaging utilizes radiolabeled molecules to non-invasively assess PD-(L)1 expression spatially and temporally. Several PD-(L)1 PET tracers have been tested in preclinical and clinical studies, with clinical trials in progress to assess their use in a number of cancer types. This review will showcase the development of PD-(L)1 PET tracers from preclinical studies through to clinical use, and will explore the opportunities in drug development and possible future clinical implementation.