Preclinical antibody-PET imaging of PD-L1

Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) blockade, including antibody therapeutics, has transformed cancer treatment. However, a major challenge in the field relates to selecting patients who are likely to respond to immune checkpoint inhibitors. Indeed, biopsy-based diagnostic tests to determine immune checkpoint protein levels do not accurately capture the inherent spatial and temporal heterogeneity of PD-L1 tumor expression. As a result, not all PD-L1-positive tumors respond to immunotherapies, and some patients with PD-L1-negative tumors have shown clinical benefits. In 2018, a first-in-human study of the clinically-approved anti-PD-L1 antibody Atezolizumab labeled with the positron emitter zirconium-89 validated the ability of positron emission tomography (PET) to visualize PD-L1 expression in vivo and predict tumor response to immunotherapy. These studies have triggered the expansion of PD-L1-targeted immunoPET to assess PD-L1 protein levels and PD-L1 expression heterogeneity in real time and across the whole tumor. First, this mini-review introduces new PD-L1 PET imaging studies of the last 4 years, focusing on the expansion of preclinical tumor models and anti-PD-L1 antibodies/antibody fragments in development. Then, the review discusses how these preclinical models and targeting agents can be utilized to study spatial and temporal heterogeneity of PD-L1 expression.