Noninvasive Imaging of Macrophages in Rheumatoid Synovitis Using 11C-(R)-PK11195 and Positron Emission Tomography

Objective. Noninvasive imaging by positron emission tomography (PET) of macrophages in inflamed joints of patients with rheumatoid arthritis (RA) may allow early detection of disease activity. We undertook this study to investigate whether rheumatoid synovitis can be visualized by PET using the tracer C-11-(R)PK11195, which binds to peripheral benzodiazepine receptors (PBRs) on macrophages. Methods. Knee joints of 11 RA patients with active arthritis of at least I knee joint were imaged with C-11-(R)-PK11195 PET. Tissue uptake of C-11-(R)PK11195 was quantified. PET was followed by arthroscopy of the most inflamed knee joint of each RA patient. Synovial tissue samples were subjected to immunohistochemical staining. Results. C-11-(R)-PK11195 uptake on the PET scans was significantly higher in severely inflamed joints than in joints with moderate or mild signs of inflammation. In addition, tracer uptake in contralateral uninflamed knee joints of RA patients was significantly higher than in uninflamed joints of control patients without inflammatory joint disease, suggesting the presence of subclinical disease activity. PET tracer uptake in joints correlated significantly with PBR staining in the sublining of synovial tissue. PBR staining correlated significantly with CD68 staining of macrophages. Conclusion. C-11-(R)-PK11195 PET imaging allows noninvasive in vivo imaging of macrophages in rheumatoid synovitis and possibly even in subclinical synovitis. Noninvasive visualization of macrophages may be useful both for detecting early synovitis and for monitoring synovitis activity during treatment.