van der Laken Conny J, Elzinga Ernst H, Kropholler Mark A, Molthoff Carla F M, van der Heijden Joost W, Maruyama Kaoru, Boellaard Ronald, Dijkmans Ben A C, Lammertsma Adriaan A, Voskuyl Alexandre E
VU University Medical Center, Amsterdam, The Netherlands.
Arthritis Rheum. 2008 Nov;58(11):3350-5. doi: 10.1002/art.23955.
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 11C-(R)-PK11195, which binds to peripheral benzodiazepine receptors (PBRs) on macrophages.
Knee 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.
11C-(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.
11C-(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.
通过正电子发射断层扫描(PET)对类风湿关节炎(RA)患者炎症关节中的巨噬细胞进行无创成像,可能有助于早期发现疾病活动。我们开展本研究以调查使用与巨噬细胞外周苯二氮䓬受体(PBRs)结合的示踪剂11C-(R)-PK11195,PET是否能使类风湿滑膜炎显影。
对11例至少有1个膝关节活动性关节炎的RA患者的膝关节进行11C-(R)-PK11195 PET成像。对11C-(R)-PK11195的组织摄取进行定量分析。PET检查后,对每位RA患者炎症最严重的膝关节进行关节镜检查。对滑膜组织样本进行免疫组织化学染色。
PET扫描中,严重炎症关节对11C-(R)-PK11195的摄取显著高于有中度或轻度炎症迹象的关节。此外,RA患者对侧未发炎膝关节的示踪剂摄取显著高于无炎性关节疾病的对照患者的未发炎关节,提示存在亚临床疾病活动。关节中PET示踪剂摄取与滑膜组织下层的PBR染色显著相关。PBR染色与巨噬细胞的CD68染色显著相关。
11C-(R)-PK11195 PET成像可对类风湿滑膜炎甚至可能对亚临床滑膜炎中的巨噬细胞进行无创体内成像。巨噬细胞无创显影可能对早期滑膜炎检测及治疗期间滑膜炎活动监测均有用。