Barrera P, Oyen W J G, Boerman O C, van Riel P L C M
Department of Rheumatology, University Medical Centre, Nijmegen, The Netherlands.
Ann Rheum Dis. 2003 Sep;62(9):825-8. doi: 10.1136/ard.62.9.825.
To investigate the biodistribution and specific targeting for tumour necrosis factor (TNF) of a fully human, radiolabelled anti-TNF monoclonal antibody (anti-TNF mAb) in patients with active rheumatoid arthritis (RA). To assess whether this agent is suitable for visualisation of synovitis.
Ten patients with RA underwent whole body scintigraphy after administration of a tracer-subtherapeutic dose of 100 microg (99m)Tc human anti-TNF mAb. After two weeks, the procedure was repeated to assess the specificity of the radiolabelled antibody for TNF and its sensitivity for changes in inflammation. Therefore, a competition study was performed in five patients, who received excess unlabelled anti-TNF mAb before the tracer dose of (99m)Tc-anti-TNF. Another five patients received 120 mg methylprednisolone two days before the second scintigraphy.
Radiolabelled anti-TNF mAb allowed clear visualisation of inflamed joints in patients with active RA with a high specificity. Concomitant administration of excess unlabelled anti-TNF reduced the joint uptake of (99m)Tc-anti-TNF mAb by a median of 25% as a percentage of the injected dose after 24 hours, whereas uptake in liver and spleen remained unchanged. Systemic corticosteroids reduced the disease activity, which was mirrored by a decreased joint uptake of the tracer. The anti-TNF mAb retained its high affinity for TNF alpha after labelling and was cleared from the circulation with an elimination half life of 48 hours. The procedure was well tolerated.
Radiolabelled human anti-TNF mAb allows visualisation of synovitis in patients with RA. Joint accumulation of this agent is partly due to specific TNF targeting and is highly predictive for inflammation.
研究放射性标记的全人源抗肿瘤坏死因子（TNF）单克隆抗体（抗TNF单克隆抗体）在活动性类风湿关节炎（RA）患者体内的生物分布及对TNF的特异性靶向作用。评估该药物是否适用于滑膜炎的显像。
10例RA患者在给予示踪剂治疗剂量100微克（99m）锝人抗TNF单克隆抗体后进行全身闪烁扫描。两周后，重复该操作以评估放射性标记抗体对TNF的特异性及其对炎症变化的敏感性。因此，对5例患者进行了竞争研究，这些患者在给予（99m）锝-抗TNF示踪剂量之前接受了过量的未标记抗TNF单克隆抗体。另外5例患者在第二次闪烁扫描前两天接受120毫克甲泼尼龙。
放射性标记的抗TNF单克隆抗体能够清晰显示活动性RA患者的炎症关节，特异性高。同时给予过量未标记的抗TNF可使（99m）锝-抗TNF单克隆抗体在关节的摄取量在24小时后以注射剂量的百分比计算中位数降低25%，而肝脏和脾脏的摄取量保持不变。全身用皮质类固醇降低了疾病活动度，这反映在示踪剂关节摄取量的减少上。抗TNF单克隆抗体标记后对TNFα仍保持高亲和力，从循环中清除的消除半衰期为48小时。该操作耐受性良好。
放射性标记的人抗TNF单克隆抗体可用于RA患者滑膜炎的显像。该药物在关节的蓄积部分归因于对TNF的特异性靶向作用，对炎症具有高度预测性。
