New targets for PET imaging of inflammation

Positron emission tomography (PET) plays an established role in the evaluation of infectious and inflammatory disorders, with [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) remaining the most widely used tracer in clinical practice. Its broad availability, high sensitivity, and whole-body capability have supported its use in conditions such as fever or inflammation of unknown origin, large-vessel vasculitis, sarcoidosis, inflammatory bowel disease, retroperitoneal fibrosis, and immunoglobulin G4-related disease. However, [¹⁸F]FDG has important limitations, including reduced specificity, limited performance in sites of high physiologic uptake, and susceptibility to confounding factors such as hyperglycemia and corticosteroid therapy. These shortcomings have stimulated growing interest in alternative PET radiopharmaceuticals targeting distinct inflammatory pathways. This review summarizes the current clinical landscape of most relevant non-[¹⁸F]FDG PET tracers investigated in human inflammatory disorders, including fibroblast activation protein inhibitor radioligands, radiolabeled somatostatin analogues, translocator protein tracers, chemokine receptor 4-directed agents, folate receptor ligands, immuno-PET approaches, and bacteria-specific tracers. Available evidence suggests that these agents may provide complementary information on fibroblast activation, immune-cell recruitment, neuroinflammation, macrophage activity, or pathogen-specific processes, thereby improving lesion characterization in selected settings. Among them, fibroblast activation protein inhibitor PET and somatostatin receptor-targeted PET appear particularly promising, although data remain heterogeneous and mostly preliminary. Overall, emerging PET tracers have the potential to refine the noninvasive assessment of inflammatory disease, but larger prospective studies and standardization of imaging protocols are needed before broader clinical integration.