Radionuclide Imaging for Tracking Mesenchymal Stem Cell Therapy in Knee Osteoarthritis: Current Status and Pathways to Clinical Translation

Knee osteoarthritis (KOA) is a common degenerative joint disease, and mesenchymal stem cell (MSC) therapy has emerged as a promising regenerative treatment option. However, the clinical translation of MSC therapy faces significant challenges, particularly in effectively monitoring the in vivo behavior of MSCs, including their survival, biodistribution, and functional integration. This review provides a comprehensive examination of the current landscape of radionuclide imaging techniques, particularly positron emission tomography (PET) and single-photon emission computed tomography (SPECT), for tracking MSCs in the treatment of KOA. It outlines the primary challenges associated with these imaging methods, including limitations related to radiotoxicity, tracer efflux, and the precision of quantitative cell tracking. Furthermore, the review discusses the potential of multimodal imaging and artificial intelligence (AI)-driven automated analysis to address these challenges, facilitating more accurate and functional monitoring of MSCs and their therapeutic effects. The review concludes by outlining future research directions, with an emphasis on the development of improved labeling methods, optimized imaging technologies, and enhanced integration of AI into clinical applications. These advancements are crucial for bridging the gap between preclinical findings and clinical practice, ultimately establishing radionuclide imaging as a potentially valuable tool for the clinical management of KOA.