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[放射性标记的单克隆抗体Nd2 F(ab')2片段的生物分布及γ干扰素对人胰腺肿瘤异种移植裸鼠肿瘤定位的增强作用]

[Biodistribution of radiolabeled F(ab')2 fragment of monoclonal antibody Nd2 and gamma-interferon enhancement on tumor localization in nude mice with human pancreatic tumor xenografts].

作者信息

Kondo Y

机构信息

First Department of Surgery, Osaka City University Medical School, Japan.

出版信息

Nihon Geka Gakkai Zasshi. 1995 Feb;96(2):97-105.

PMID:7708049
Abstract

Nd2 is a murine monoclonal antibody of subclass IgG1 directed against purified mucin of human pancreatic cancer cell line SW1990. A previous biodistribution and radioimmunoimaging study of Nd2 demonstrated that the tumor accumulation rate of Nd2 was excellent and that apparently positive images of xenografts could be obtained using indium-111-labeled Nd2. In this study, I first investigated the biodistribution of F(ab')2 fragment on Nd2 on SW1990 bearing nude mice. I then tested the effects of intraperitoneally administered IFN-gamma on the rate of accumulation of Nd2 in the xenografts. F(ab') fragment of Nd2 showed more rapid maximal accumulation in the tumor and more urinary excretion in earlier period than whole Nd2. F(ab')2 fragment in the blood was lower in response more urinary excretion and tissue to blood ratio was therefore much higher than that of whole Nd2 at 12 hours and 1 day after administration. The biodistribution study to determine the effects of IFN-gamma on SW1990 bearing nude mice demonstrated that the accumulation rate of Nd2 in the tumor receiving intraperitoneal administration of IFN-gamma was significantly higher than that of control group. The results of these studies suggest that F(ab')2 fragment of Nd2 is useful in some respects in clinical use and that supplementary use of IFN-gamma may improve the rate of accumulation in the tumor.

摘要

Nd2是一种亚类为IgG1的鼠单克隆抗体,它针对人胰腺癌细胞系SW1990的纯化粘蛋白。先前对Nd2的生物分布和放射免疫成像研究表明,Nd2的肿瘤蓄积率极佳,并且使用铟-111标记的Nd2能够获得明显阳性的异种移植瘤图像。在本研究中,我首先研究了Nd2的F(ab')2片段在荷SW1990裸鼠体内的生物分布。然后我测试了腹腔注射γ干扰素对Nd2在异种移植瘤中蓄积率的影响。Nd2的F(ab')片段在肿瘤中的最大蓄积比完整的Nd2更快,且在早期尿排泄更多。血液中的F(ab')2片段因更多的尿排泄而含量更低,因此给药后12小时和1天时组织与血液的比率远高于完整的Nd2。确定γ干扰素对荷SW1990裸鼠影响的生物分布研究表明,腹腔注射γ干扰素的肿瘤中Nd2的蓄积率显著高于对照组。这些研究结果表明,Nd2的F(ab')2片段在临床应用的某些方面是有用的,并且补充使用γ干扰素可能会提高在肿瘤中的蓄积率。

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