Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized contemporary oncology, presenting efficacy in various solid tumors and lymphomas. However, ICIs may potentially overstimulate the immune system, leading to immune-related adverse events (irAEs). IrAEs may affect multiple organs, such as the colon, stomach, small intestine, kidneys, skin, lungs, joints, liver, lymph nodes, bone marrow, brain, heart, and endocrine glands (e.g., pancreas, thyroid, or adrenal glands), exhibiting autoimmune inflammation. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) is commonly used in oncology for staging and assessment of therapy responses, but it may also serve as a tool for detecting irAEs. This review aims to present various patterns of metabolic activation associated with irAEs due to ICI treatment, identifiable through ¹⁸F-FDG PET/CT. It describes the advantages of early detection of irAEs, but also presents the challenges in differentiating them from tumor progression. It also delves into aspects of molecular response assessment within the context of pseudoprogression and hyperprogression, along with typical imaging findings related to these phenomena. Lastly, it summarizes the role of functional PET imaging in oncological immunotherapy, speculating on its future significance and limitations.

Background: Oligometastatic non-small cell lung cancer (OMD NSCLC) represents a distinct clinical state with limited metastatic spread, where local ablative therapies (LAT) combined with systemic treatment may improve outcomes. Accurate staging and prognostic assessment are critical, with ¹⁸F-FDG PET/CT emerging as a valuable tool for detecting metabolically active tumor burden. Results: We retrospectively analyzed 38 patients with synchronous OMD NSCLC who received radiotherapy. All patients underwent ¹⁸F-PET/CT and brain imaging for staging. Semi-quantitative ¹⁸F-PET/CT parameters, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary tumor and metastatic lesions, were measured and associated with progression-free survival (PFS) and overall survival (OS) using Cox proportional hazard models. The median PFS and OS were 8.28 and 21.62 months, respectively. Higher MTV and TLG values of metastases were significantly associated with shorter PFS and OS (p < 0.01). In multivariable analysis, TLG of metastases above the median remained an independent predictor of worse PFS (HR = 2.78, p = 0.031) and OS (HR = 3.12, p = 0.024), alongside clinical factors such as ECOG performance status 2 and having multiple metastases. The metabolic parameters of the primary tumor did not predict survival outcomes. Conclusions:¹⁸F-PET/CT-derived metabolic parameters, particularly the TLG of metastatic lesions, may provide significant prognostic information in oligometastatic NSCLC beyond clinical variables. These findings may support the integration of ¹⁸F-PET/CT metrics for future trials involving patients treated with LAT in oligometastatic NSCLC.