Clinical Application of ImmunoPET Targeting Checkpoint Inhibitors

Simple Summary Cancer treatment with immune checkpoint inhibitors (ICIs) has significantly impacted patients' management and outcomes. To better assess the benefit of ICIs and reduce the risk of treatment-induced side-effects, new predictive biomarkers have been investigated. From a molecular imaging point of view, several PET tracers have been developed to examine the immune checkpoint (IC) status and the characteristics of the tumor microenvironment (TME). Herein, we present the most relevant data on ImmunoPET-targeting ICs and tumor-infiltrating lymphocytes (TILs), with a main focus on the latest developments in clinical molecular imaging studies of solid tumors.Abstract In the last decade, monoclonal antibodies (mAbs) targeting CTLA-4, PD-1, or PD-L1 have been developed and immune checkpoint inhibitors (ICIs) have become the main approach in cancer immunotherapy. However, not all patients benefit from ICI therapy and some are at risk of developing treatment-induced side-effects. These aspects, in parallel with the imaging challenges related to response assessments during immunotherapy, have driven scientific research to the discovery of new predictive biomarkers to individualize patients who could benefit from ICIs. In this context, molecular imaging using PET (positron emission tomography), which allows for whole-body tumor visualization, may be a promising non-invasive method for the determination of patients' sensitivity to antibody drugs. Several PET tracers, diverse from 2-[18F]FDG (or 2-Deoxy-2-[18F]fluoroglucose), have been developed to image immune checkpoints (ICs) or key elements of the immune system, although most of them are still in preclinical phases. Herein, we present the current state of the ImmunoPET-targeting of IC proteins with mAbs and antibody fragments, with a main focus on the latest developments in clinical molecular imaging studies of solid tumors. Moreover, given the relevance of the immune system and of tumor-infiltrating lymphocytes in particular in the prediction of the benefit of ICIs, we dedicate a portion of this review to ImmunoPET-targeting T cells.