Visualizing inflammation activity in rheumatoid arthritis with Tc-99 m Anti-CD4-mAb fragment scintigraphy

Visualizing inflammation activity in rheumatoid arthritis with Tc-99 m Anti-CD4-mAb fragment scintigraphy
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DOI:
10.1016/j.nucmedbio.2013.12.018
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发表时间:
2014-04-01
影响因子:
3.1
通讯作者:
Sabri, O.
Sabri, O.
中科院分区:
医学4区
文献类型:
--
作者:
Steinhoff, K.;Pierer, M.;Sabri, O.

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目的:T细胞定位的CD 4抗原是类风湿关节炎(RA)的治疗靶点之一。然而,到目前为止,还没有建立成像工具来可视化体内的这个目标。我们的研究的目的是评估的安全性和耐受性的锝-99米标记的鼠抗人CD 4抗体IgG 1-Fab片段([Tc-99米]-抗CD 4-Fab,[Tc-99米]-EP 1645)在患者活动性滑膜炎由于RA,并评估其作为疾病activity.Methods的标志物的潜力:在目前的阶段I的原则研究的证据5例RA进行了检查。全身,手,脚的平面扫描后30分钟至24小时应用550 +/- 150 MBq [Tc-99 m]-anti-CD 4-Fab,随后进行视觉分析,在68个关节每例患者和半定量分析手和腕关节的临床数据进行比较。未观察到人抗鼠抗体滴度增加。所有患者在近70%的临床受累关节中扫描呈阳性。阳性扫描也发现在8%的关节没有证据肿胀或tenert.Conclusion:闪烁显像与[Tc-99 m]-anti-CD 4-Fab是一种很有前途的技术,用于评估RA患者的炎症活动,CD 4状态和治疗控制的治疗前评估。临床不明显关节中的示踪剂摄取强烈表明[Tc-99 m]-抗CD 4-Fab的诊断潜力。这项技术是否有资格作为RA的预后因素,需要在进一步的研究中进行分析,以及缺乏示踪剂摄取的临床受累关节的病理生理学背景。(C)2014年爱思唯尔公司All rights reserved.
Purpose: T-cell-located CD4 antigen represents one of the therapeutic targets in rheumatoid arthritis (RA). However, up to now there is no established imaging tool to visualize this target in vivo. The aim of our study was to assess the safety and tolerability of a technetium-99 m labelled murine anti-human CD4 IgG1-Fab fragment ([Tc-99m]-anti-CD4-Fab, [Tc-99m]-EP1645) in patients with active synovitis due to RA, and to evaluate its potential as a marker of disease activity.Methods: In the present phase I proof of principle study five patients with RA were examined. Planar scans of the whole body, hands, and feet were taken 30 min up to 24 h after application of 550 +/- 150 MBq [Tc-99m]-anti-CD4-Fab, followed by visual analyses, comparison with clinical data in 68 joints per patient and semiquantitative analysis of hand and wrist joints.Results: Neither infusion related adverse events nor adverse events during follow up were observed. No increase in human anti-murine antibody titres was seen. All patients had positive scans in almost 70% of clinically affected joints. Positive scans were also found in 8% of joints without evidence of swelling or tenderness.Conclusion: Scintigraphy with [Tc-99m]-anti-CD4-Fab is a promising technique for evaluation of inflammatory activity in patients with RA, pre-therapeutical evaluation of CD4 status and therapy control. Tracer uptake in clinically inconspicuous joints strongly indicates diagnostic potential of [Tc-99m]-anti-CD4-Fab. Whether this technique is eligible as a prognostic factor in RA needs to be analysed in further studies as well as the pathophysiological background of clinically affected joints lacking tracer uptake. (C) 2014 Elsevier Inc. All rights reserved.