Advances in molecular imaging for osteoarthritis.

Osteoarthritis (OA) is a complex, multifactorial joint disease and a leading contributor to global disability. Despite its high prevalence and socioeconomic burden, no curative or preventive therapies currently exist. The ability to detect early OA, or even "pre-OA" could provide the opportunity for earlier interventions. Current conventional imaging modalities such as radiography and Magnetic resonance imaging (MRI) are limited by their inability to detect early pathophysiological molecular changes. This review highlights the potential of positron emission tomography (PET) imaging to transform the diagnosis and therapeutic monitoring of OA. PET has emerged as a transformative tool capable of visualizing early metabolic, inflammatory, and cellular alterations. But while current clinical PET imaging with [18F]Fluorodeoxyglucose ([18F]-FDG) and [18F] Sodium fluoride ([18F]-NaF) can assess synovial inflammation and subchondral bone remodeling, their lack of specificity hinders further advances. We also review the recent development of radiotracers targeting specific immune and mesenchymal cell populations, such as translocator protein (TSPO) and fibroblast activation protein inhibitor (FAPI) that have demonstrated potential for characterizing the inflammatory endotype in OA and monitoring treatment response. Given the lack of validated cell-specific tracers, limited studies in early-stage or asymptomatic OA, and few longitudinal data sets, future research should prioritize development and validation of pathophysiology-specific tracers and incorporation of PET into longitudinal and interventional studies. This evolving field holds promise not only for advancing OA preclinical research but also for informing precision diagnostics and early therapeutic strategies in clinical practice.