Longitudinal CCR2 PET Imaging Tracks Early Inflammatory Monocyte and Macrophage Infiltration in Experimental Arthritis

Objective. Recruitment of C-C motif chemokine receptor 2 (CCR2+) inflammatory monocytes and macrophages represent an early event in rheumatoid arthritis (RA) pathogenesis that cannot be tracked noninvasively with existing imaging modalities. We evaluated longitudinal Ga-DOTA-ECL1i positron emission tomography/computed tomography (PET/CT) to track and quantify CCR2 cell recruitment in experimental inflammatory arthritis. Methods. Longitudinal Ga-DOTA-ECL1i PET/CT imaging was performed in K/BXN serum transfer arthritis (STA) mice. Imaging findings were validated using biodistribution, autoradiography, histopathology, immunofluorescence, microCT, cytokine profiling, clinical assessment, and pain-related behavioral testing. Results. Joint Ga-DOTA-ECL1i uptake increased during the acute arthritis and declined with disease resolution. Increased tracer signal localized to inflamed joints, coinciding with CCR2 monocyte and macrophage infiltration, synovial inflammation, cartilage damage, local CCL2 elevation, and mechanical allodynia. PET uptake correlated with ankle swelling, clinical disease severity, pain, and paw CCL2 levels, with peak tracer signal preceding progressive structural bone remodeling. Conclusion. Longitudinal Ga-DOTA-ECL1i PET/CT enables noninvasive visualization and quantification of early CCR2 monocyte and macrophage recruitment, establishing CCR2 PET imaging as a mechanism-based molecular platform for early detection, risk stratification, and therapeutic monitoring in inflammatory arthritis.