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用放射性标记抗体靶向癌症。成像与治疗的前景。

Targeting of cancer with radiolabeled antibodies. Prospects for imaging and therapy.

作者信息

Goldenberg D M

机构信息

Center for Molecular Medicine and Immunology, University of Medicine and Dentistry, New Jersey, Newark 07103.

出版信息

Arch Pathol Lab Med. 1988 Jun;112(6):580-7.

PMID:3288167
Abstract

This article reviews the current status, including problems and some proposed solutions, of the targeting of cancer with radioactive antibodies for use in antibody imaging (radioimmunodetection) and radioimmunotherapy. The problems and results are similar for purified polyclonal and murine monoclonal antibodies. Foremost among the problems are the low accretion of antibody (0.01% to 0.001% of injected dose per gram) in tumor and the nonspecific deposition of radiometals that are more ideal for imaging or therapy after antibody conjugation. Despite these limitations, radioimmunodetection appears to be a safe and useful method, even at this early stage of development. Sensitivity, specificity, and accuracy rates of 80% to 90% have been achieved in some studies involving radioiodine labels and polyclonal or monoclonal antibodies, whereas lower percentages have been achieved with indium 111 or technetium Tc 99m radioconjugates. Even at a usual tumor resolution of 1.5 to 2.0 cm, occult cancers have been disclosed by radioimmunodetection when missed by traditional detection measures, including computed tomography and magnetic resonance imaging. Radioimmunotherapy is somewhat less developed as a treatment modality, but encouraging remissions have been observed, thus stimulating further active pursuit of this technology. These targeting results have been achieved with antibodies that are not truly cancer specific, but only exploit quantitative differences in antigen expression between tumor and adjacent normal tissues. Circulating target tumor antigens do not appear to prevent successful tumor targeting of the radioactive antibodies.

摘要

本文综述了放射性抗体靶向癌症在抗体成像(放射免疫检测)和放射免疫治疗中的现状,包括存在的问题及一些提出的解决方案。对于纯化的多克隆抗体和鼠单克隆抗体,问题和结果相似。其中最主要的问题是肿瘤中抗体的摄取率低(每克肿瘤组织摄取的注射剂量为0.01%至0.001%),以及放射性金属在抗体偶联后用于成像或治疗时的非特异性沉积。尽管存在这些局限性,但即使在目前的早期发展阶段,放射免疫检测似乎仍是一种安全且有用的方法。在一些涉及放射性碘标记和多克隆或单克隆抗体的研究中,灵敏度、特异性和准确率达到了80%至90%,而使用铟111或锝Tc 99m放射性偶联物时的百分比则较低。即使在通常1.5至2.0厘米的肿瘤分辨率下,放射免疫检测也能发现传统检测方法(包括计算机断层扫描和磁共振成像)遗漏的隐匿性癌症。放射免疫治疗作为一种治疗方式的发展程度稍低,但已观察到令人鼓舞的缓解情况,从而刺激了对该技术的进一步积极探索。这些靶向结果是通过并非真正癌症特异性的抗体实现的,这些抗体只是利用了肿瘤与相邻正常组织之间抗原表达的定量差异。循环中的靶肿瘤抗原似乎并未妨碍放射性抗体对肿瘤的成功靶向。

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