Jamar F, Houssiau F A, Devogelaer J-P, Chapman P T, Haskard D O, Beaujean V, Beckers C, Manicourt D-H, Peters A M
Centre of Nuclear Medicine, University of Louvain Medical School, Brussels, Belgium.
Rheumatology (Oxford). 2002 Jan;41(1):53-61. doi: 10.1093/rheumatology/41.1.53.
We previously described a novel radiolabelled monoclonal antibody (1.2B6), which reacts with porcine E-selectin, for targeting activated endothelium as a means of imaging inflammatory disorders, and presented initial clinical work based on (111)In-labelled antibody. The aim of the present study was to evaluate a Fab fragment of 1.2B6 labelled with (99m)Tc in patients with rheumatoid arthritis (RA) by comparison with (i) (111)In-labelled 1.2B6 F(ab')(2) and (ii) conventional bone scanning.
(99m)Tc-1.2B6-Fab ( approximately 440 MBq) and (111)In-1.2B6-F(ab')(2) ( approximately 27 MBq) were compared in 10 patients using a double-isotope protocol. Images were obtained 4 and 20-24 h after injection. Two normal volunteers were also imaged. In a separate group of 16 patients, (99m)Tc-1.2B6-Fab and (99m)Tc-oxidronate ((99m)Tc-HDP) ( approximately 740 MBq) were compared on the basis of visual and semi-quantitative analysis of joint uptake (joint/soft tissue ratios) 4 h after injection. The respective biodistributions and blood clearances of the two 1.2B6 fragments were also compared.
Image contrast was slightly better with (99m)Tc-Fab at 4 h but equal for the two tracers at 24 h. Diagnostic accuracy, taking joint tenderness or swelling as the clinical endpoint, was 76% for both fragments at 24 h. Plasma clearance of (99m)Tc-Fab was faster than that of (111)In-F(ab')(2) (t(1/2) 142 vs 421 min; P<0.0001). (99m)Tc-Fab appeared somewhat unstable in vivo, as shown by activity in the thyroid gland and bowel. The diagnostic accuracy of (99m)Tc-Fab was 88%, higher than that of (99m)Tc-HDP (57%) as a result of the low specificity of the latter in RA. Receiver operating characteristic (ROC) curve analysis using joint/soft tissue ratios as a variable cut-off showed that (99m)Tc-Fab discriminates better than (99m)Tc-HDP between actively inflamed and silent joints (Z=4.72; P<0.0001). No uptake of (99m)Tc-Fab was observed by inactive or normal joints, whereas (99m)Tc-HDP was taken up by all joints to a variable degree, making the decision as to whether a particular joint is actively involved or chronically damaged very difficult.
(99m)Tc-anti-E-selectin-Fab scintigraphy can be used successfully to image synovitis with better specificity than (99m)Tc-HDP bone scanning. The advantages over (111)In-1.2B6-F(ab')(2) are easier availability of the radionuclide, improved physical properties and optimal imaging 4 h after injection.
我们之前描述了一种新型放射性标记单克隆抗体（1.2B6），它可与猪E选择素反应，用于靶向活化内皮细胞，作为成像炎症性疾病的一种手段，并展示了基于铟 - 111标记抗体的初步临床研究。本研究的目的是通过与（i）铟 - 111标记的1.2B6 F（ab'）₂和（ii）传统骨扫描相比较，评估用锝 - 99m标记的1.2B6的Fab片段在类风湿关节炎（RA）患者中的情况。
采用双同位素方案，在10例患者中比较了锝 - 99m - 1.2B6 - Fab（约440 MBq）和铟 - 111 - 1.2B6 - F（ab'）₂（约27 MBq）。注射后4小时和20 - 24小时获取图像。还对两名正常志愿者进行了成像。在另一组16例患者中，基于注射后4小时关节摄取（关节/软组织比值）的视觉和半定量分析，比较了锝 - 99m - 1.2B6 - Fab和锝 - 99m - 奥曲膦（锝 - 99m - HDP）（约740 MBq）。还比较了两种1.2B6片段各自的生物分布和血液清除情况。
4小时时锝 - 99m - Fab的图像对比度略好，但24小时时两种示踪剂的图像对比度相同。以关节压痛或肿胀作为临床终点，24小时时两种片段的诊断准确性均为76%。锝 - 99m - Fab的血浆清除速度比铟 - 111 - F（ab'）₂快（半衰期分别为142分钟和421分钟；P < 0.0001）。锝 - 99m - Fab在体内似乎有些不稳定，如甲状腺和肠道出现放射性活性所示。锝 - 99m - Fab的诊断准确性为88%，高于锝 - 99m - HDP（57%），因为后者在RA中的特异性较低。以关节/软组织比值作为可变截断值的受试者操作特征（ROC）曲线分析表明，在区分活跃发炎关节和静止关节方面，锝 - 99m - Fab比锝 - 99m - HDP表现更好（Z = 4.72；P < 0.0001）。未观察到无活性或正常关节摄取锝 - 99m - Fab。而锝 - 99m - HDP被所有关节不同程度摄取，这使得判断某个特定关节是活跃受累还是慢性受损非常困难。
锝 - 99m - 抗E选择素 - Fab闪烁扫描术可成功用于成像滑膜炎，其特异性优于锝 - 99m - HDP骨扫描。与铟 - 111 - 1.2B6 - F（ab'）₂相比，其优势在于放射性核素更容易获得、物理性质改善以及注射后4小时成像最佳。
