ObjectiveNoninvasive 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 11C‐(R)‐PK11195, which binds to peripheral benzodiazepine receptors (PBRs) on macrophages.MethodsKnee joints of 11 RA patients with active arthritis of at least 1 knee joint were imaged with 11C‐(R)‐PK11195 PET. Tissue uptake of 11C‐(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.Results11C‐(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.Conclusion11C‐(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.
18 F-FDG PET is a sensitive, promising method for visualizing disease activity in rheumatoid arthritis. This study aimed to assess the association between changes in 18 F-FDG joint uptake after 2 wk of infliximab treatment and clinical outcome. Methods: Scans were obtained at the initiation of treatment and at 2 wk. Uptake in metacarpophalangeal and wrist joints was quantified using standardized uptake values. Results: Changes in mean standardized uptake value at 0-2 wk significantly correlated with the disease activity score (DAS) at 14 and 22 wk and contributed significantly to the prediction of DAS at these time points. No significant correlation was found between changes in acute-phase reactants at 0-2 wk and the DAS at later time points. Conclusion: Early changes in 18 F-FDG uptake in joints during infliximab treatment of rheumatoid arthritis patients, using PET, may predict clinical outcome. Rheumat oid arthritis (RA) is a disabling joint disease.Stringent monitoring of disease activity and, if necessary, changing to another, more effective, drug treatment has been shown to improve the outcome of patients (1).Anti-tumor necrosis factor (TNF) a-blocking agents, such as infliximab, potently bind TNF and block inflammation by inhibiting the downstream effects of this cytokine. Anti-TNF treatment is effective in reducing disease activity and improving outcome, although not in all patients (2).In general, the response to anti-TNF treatment is assessed between 14 and 22 wk after initiation of the drug. At present, there are no markers that can predict response to anti-TNF treatment at an earlier stage (3-6). Considering the high costs of anti-TNF treatment, that is, $30,500-$38,700 per discounted quality-adjusted life-year gained (7), early prediction of response could reduce the overall costs of treatment.Several reports have shown that inflammation in synovial tissue in RA patients can be detected using 18 F-FDG PET (8-12). Therefore, 18 F-FDG PET may be an interesting tool to assess response early during anti-TNF treatment.This explorative study investigated the potential ability of early 18 F-FDG PET changes to predict clinical outcome at a later stage. MATERIALS AND METHODS Patients and Study ProtocolAll patients (11 women, 5 men) fulfilled the American College of Rheumatology criteria for RA (13). The presence of at least 2 metacarpophalangeal or wrist joints with signs of arthritis was required. Patients were treated with infliximab, and infusions were administered at 0, 2, 6, 14, and 22 wk. At all time points, tenderness and swelling of proximal interphalangeal and metacarpophalangeal joints of hands, elbows, shoulders, and knees (28 joints in total) were determined. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured, and the disease activity scores (DASs) of 28 joints were calculated (14). 18 F-FDG PET scans of metacarpophalangeal and wrist joints were acquired at 0 and 2 wk. Informed consent was obtained of all participating patients. The protocol was approved by the local ...
Purpose: Previous positron emission tomography (PET) studies have shown increased 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake in joints of patients with osteoarthritis (OA) and inflamed joints of patients with rheumatoid arthritis (RA). This study compares FDG uptake in joints of RA and OA patients and FDG-uptake with clinical signs of inflammation. Procedures: FDG-PET scans of hands and wrists were performed in patients with RA and primary OA. PET data were compared with clinical data. Results: 29% of RA joints and 6% of OA joints showed elevated FDG-uptake. The level of uptake in PET-positive OA joints was not significantly different from that in RA joints. The majority of PET results of RA joints corresponded with clinical findings. Clinical synovitis was found some OA joints with FDG-uptake. Conclusions: FDG-uptake was observed in the majority of clinically inflamed RA joints and in a few OA joints with no significant difference in uptake level. The latter may be due to secondary synovitis.
Purpose Rheumatoid arthritis (RA) involves migration of macrophages into inflamed areas. (R)-[11 C]PK11195 binds to peripheral benzodiazepine receptors, expressed on macrophages, and may be used to quantify inflammation using positron emission tomography (PET). This study evaluated methods for the quantification of (R)- Conclusion (R)-[11 C]PK11195 kinetics in the knee were best described by a reversible single-tissue compartment model including blood volume. Applying metabolite corrections did not increase sensitivity. Due to the high correlation with V d , SUV is a practical alternative for clinical use.
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