Department of Nuclear Medicine and Molecular Imaging, University of Groningen, Groningen, The Netherlands.
Eur J Nucl Med Mol Imaging. 2010 Feb;37(2):386-98. doi: 10.1007/s00259-009-1272-0. Epub 2009 Sep 24.
The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-alpha, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with (99m)Tc or (111)In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform 'evidence-based biological therapy' of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for therapy decision-making and follow-up.
上个世纪末，为类风湿关节炎（RA）患者的炎症成像和治疗提供了多种方法。生物疗法的引入开创了治疗手段的革命，开发了几种新型单克隆抗体（mAbs），这些 mAbs 可以是鼠源、嵌合、人源化和全人源抗体。单克隆抗体特异性地与它们的靶标结合，靶标可以是粘附分子、活化标志物、抗原或受体，从而在分子水平上干扰特定的炎症途径，导致潜在致病过程的免疫调节。这些新一代 mAbs 还可以通过直接或间接方法用各种核素进行放射性标记，具体取决于特定的诊断应用。为了研究类风湿关节炎患者，已经对几种单克隆抗体及其片段进行了放射性标记，包括抗 TNF-α、抗 CD20、抗 CD3、抗 CD4 和抗 E-选择素抗体，主要使用 (99m)Tc 或 (111)In 进行放射性标记。这些放射性标记抗体的闪烁显像可能为 RA 患者的研究提供令人兴奋的可能性，并提供两种类型的信息：（1）通过早期检测可能难以评估的炎症关节，更好地分期疾病和诊断疾病活动状态；（2）它可能提供一种进行“基于证据的生物治疗”关节炎的可能性，以期在使用相同的未标记抗体进行治疗之前评估抗体是否会在炎症关节中定位。这对于选择接受治疗的患者可能特别重要，因为生物疗法可能会引起严重的副作用并且相当昂贵。本文综述了放射性标记 mAbs 在 RA 研究中的应用，特别强调了使用不同放射性标记的单克隆抗体进行治疗决策和随访。
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