Evaluation of response to immune checkpoint inhibitors: Is there a role for positron emission tomography?

Strategies targeting intracellular negative regulators such as immune checkpoint inhibitors (ICPIs) have demonstrated significant antitumor activity across a wide range of solid tumors. In the clinical practice, the radiological effect of immunotherapeutic agents has raised several more relevant and complex challenges for the determination of their imaging-based response at single patient level. Accordingly, it has been suggested that the conventional Response Evaluation Criteria in Solid Tumors assessment alone, based on dimensional evaluation provided by computed tomography (CT), tends to underestimate the benefit of ICPIs at least in a subset of patients, supporting the need of immune-related response criteria. Different from CT, very few data are available for the evaluation of immunotherapy by means of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, since the antineoplastic activity of ICPIs is highly related to the activation of T cells against cancer cells, FDG accumulation might cause false-positive findings. Yet, discrimination between benign and malignant processes represents a huge challenge for FDG-PET in this clinical setting. Consequently, it might be of high interest to test the complex and variegated response to ICPIs by means of PET and thus it is worthwhile to ask if a similar introduction of immune-related PET-based criteria could be proposed in the future. Finally, PET might offer a new insight into the biology and pathophysiology of ICPIs thanks to a growing number of non-invasive immune-diagnostic approaches based on non-FDG tracers.