Clinical Application of ImmunoPET Targeting Checkpoint Inhibitors

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.

Prospective Assessment of Fluorine-18-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) for Early Identification of Checkpoint-Inhibitor-Induced Pseudoprogression

“…Also, other PET tracers like 68Ga FAPI 18FLT, 11C-MET, or immuno-PET radiotracers targeting T-cells or immune checkpoint targets, may play a future role in the evaluation of response in melanoma [ 27 , 28 , 29 , 30 ].…”

Is 18F-FDG-PET/CT an Optimal Imaging Modality for Detecting Immune-Related Adverse Events after Immune-Checkpoint Inhibitor Therapy? Pros and Cons

“…In the era of rapidly developing molecular imaging, one can assume that new tracers may appear and will help understand the underlying pathophysiological mechanisms of tumor microenvironment and immune-mediated reactions. Recently, immuno-PET-enabling in vivo visualization of immune checkpoint inhibitors was presented [ 125 ]. With the advent of zirconium-89 (89Zr)-labeled nivolumab, pembrolizumab, atezolizumab, or durvalumab, it is now possible to determine the PD-1/PD-L1 expression in all tumor lesions throughout the body, without being limited to histopathological analysis of a single tissue sample.…”