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[肿瘤导向剂的最新进展——使用单克隆抗体的癌症放射免疫显像]

[Recent advances in tumor-seeking agents--radioimmunoimaging of cancers using monoclonal antibodies].

作者信息

Hashimoto S

机构信息

Dept. of Radiology, School of Medicine, Keio University.

出版信息

Gan To Kagaku Ryoho. 1988 Apr;15(4 Pt 2-1):866-72.

PMID:2455482
Abstract

Development of biotechnology has made it possible to produce monoclonal antibodies (MoAbs) which associate with tumors. Injected RN-labeled MoAbs would be expected to accumulate in specific tumors. This concept can be evaluated not only from the point of diagnosis but also the therapy of cancers. Before applying RN-labeled MoAbs to patients with cancers, certain factors influencing radioimmunodetection should be investigated, such as (1) Labeling nuclides:RN should be selected by considering its physical properties. Biodistributions of RN-labeled MoAbs differ from one RN to another. (2) Labeling method: labeling techniques and optimum conditions should be established for each MoAb, in order to retain the immunoreactivity and stability of RN-labeled MoAb in vivo. (3) Circulating antigen:RN-labeled MoAb, once injected, may be challenged by the circulating antigen in the blood. We found that uptake of MoAbs against tumor markers (AFP, DU-PAN II) into tumors (hepatoma or pancreatic tumor) was decreased, and that the background activity was increased when the concentration of AFP or DU-PAN II in the blood was high. In addition to this fundamental information with respect to each MoAb, some clinical considerations are necessary for the application of RN-MoAbs to humans, mainly possible side effects. Clinical applications of immunoscintigraphy have not been well developed in Japan, although more than 2,000 cases utilizing this technique have been reported in Europe. In Europe and the U.S.A., tumors were detected with about 70% positivity without any serious side effects. General concerns regarding MoAb products, which have been proposed by the FDA, are also discussed in this paper.

摘要

生物技术的发展使得生产与肿瘤相关的单克隆抗体(MoAbs)成为可能。注射放射性核素标记的单克隆抗体有望在特定肿瘤中蓄积。这一概念不仅可以从癌症诊断的角度进行评估,也可以从癌症治疗的角度进行评估。在将放射性核素标记的单克隆抗体应用于癌症患者之前,应研究影响放射免疫检测的某些因素,例如:(1)标记核素:应根据其物理性质选择放射性核素。不同放射性核素标记的单克隆抗体的生物分布各不相同。(2)标记方法:应为每种单克隆抗体建立标记技术和最佳条件,以保持放射性核素标记的单克隆抗体在体内的免疫反应性和稳定性。(3)循环抗原:放射性核素标记的单克隆抗体一旦注射,可能会受到血液中循环抗原的影响。我们发现,当血液中AFP或DU-PAN II的浓度较高时,针对肿瘤标志物(AFP、DU-PAN II)的单克隆抗体进入肿瘤(肝癌或胰腺肿瘤)的摄取减少,背景活性增加。除了关于每种单克隆抗体的这些基本信息外,将放射性核素标记的单克隆抗体应用于人体还需要一些临床考虑,主要是可能的副作用。尽管欧洲已报道有2000多例使用该技术的病例,但免疫闪烁成像在日本的临床应用尚未得到很好的发展。在欧洲和美国,约70%的肿瘤检测呈阳性,且无任何严重副作用。本文还讨论了美国食品药品监督管理局(FDA)提出的关于单克隆抗体产品的一般问题。

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