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放射性标记抗体在癌症成像与治疗中的生物学及临床前景

Biological and clinical perspectives of cancer imaging and therapy with radiolabeled antibodies.

作者信息

Goldenberg D M, Blumenthal R D, Sharkey R M

机构信息

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

出版信息

Semin Cancer Biol. 1990 Jun;1(3):217-25.

PMID:2103497
Abstract

Cancer and other diseases that elaborate increased quantities of antigenic substances can be targeted with suitable antibodies labeled with radionuclides. Factors influencing this targeting include the nature, pharmacology, and physiology of the antibodies, the composition and physiology of the tissue targets, the character and linkage of the radionuclide to the antibody, the choice of radionuclide, and the method of administration of the radioimmunoconjugate. The current state of cancer imaging with gamma-emitting radiolabeled antibodies, using the more optimal Fab' antibody fragments conjugated with 99mTc and imaging by single-photon emission computed tomography, permits high detection rates (90% range) of tumors at or below 0.5 cm, thus disclosing lesions missed by conventional radiographic methods. In radioimmunotherapy, severe limitations are due to low antibody accretion in tumors (resulting in low target rad doses), inadequate conjugation of radiometals to antibodies, high red marrow toxicity, and human anti-antibody responses when foreign immunoglobulins are administered. However, radiosensitive tumors, such as lymphomas, have shown impressive clinical responses.

摘要

癌症及其他能产生大量抗原性物质的疾病可用标记有放射性核素的合适抗体进行靶向治疗。影响这种靶向作用的因素包括抗体的性质、药理学和生理学特性、组织靶点的组成和生理学特性、放射性核素与抗体的特性及连接方式、放射性核素的选择以及放射免疫缀合物的给药方法。目前,使用与99mTc偶联的更优化的Fab'抗体片段,并通过单光子发射计算机断层扫描成像,利用发射γ射线的放射性标记抗体进行癌症成像,对于0.5厘米及以下的肿瘤可实现较高的检测率(90%左右),从而发现传统放射学方法遗漏的病变。在放射免疫治疗中,存在严重局限性,原因包括肿瘤中抗体蓄积量低(导致靶区辐射剂量低)、放射性金属与抗体的缀合不充分、红骨髓毒性高以及给予外源免疫球蛋白时出现人抗抗体反应。然而,对放射敏感的肿瘤,如淋巴瘤,已显示出令人瞩目的临床反应。

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