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用于免疫闪烁显像研究的小鼠单克隆抗GD3抗体在荷人黑色素瘤异种移植物裸鼠中的生物分布研究。

Biodistribution study of murine monoclonal anti-GD3 antibody in nude mice bearing human melanoma xenografts for development of immunoscintigraphy.

作者信息

Ojima F, Ido T, Kijima-Suda I, Nakagawa Y

机构信息

Department of Pharmacy, Yamagata University Hospital, Japan.

出版信息

Tohoku J Exp Med. 1998 Jun;185(2):89-100. doi: 10.1620/tjem.185.89.

Abstract

Reactivity of the monoclonal antibody with the tumor markers is known to be different between cultured cells in vitro and transplanted tumors in vivo. The monoclonal antibody should be investigated regarding its specific accumulation in tumor-bearing mice for immunodetection or immunotherapy. We studied the biodistribution of radiolabeled monoclonal anti-GD3 antibody (IgM) in normal mice and nude mice bearing human melanoma xenografts. Tissue-to-blood distribution ratios of the antibody in the liver, spleen and kidney increased with time in both normal and melanoma-transplanted mice, but no significant changes were observed in other normal tissues up to 5 days after injection. Specific accumulation of the monoclonal anti-GD3 antibody in the grafted human melanoma (HMV-II) was observed 4 and 5 days after injection. On the other hand, no specific accumulation of standard murine IgM in the tissue of HMV-II was observed in mice bearing the HMV-II xenograft 5 days after injection. Because the tissue-to-blood ratio of the distribution in the tissue of HMV-II became larger than that of other tissues 4 and 5 days after administration, 4 days after the administration of the monoclonal anti-GD3 antibody were required for immunoscintigraphy. Accumulation of the monoclonal anti-GD3 antibody in other human melanomas (HMV-I, HMY-1 and SK-MEL188) inoculated into mice was also observed 4 days after the antibody administration. The monoclonal anti-GD3 antibody used in this study would be useful in immunodetection or immunotherapy.

摘要

已知单克隆抗体与肿瘤标志物的反应性在体外培养细胞和体内移植肿瘤之间存在差异。对于免疫检测或免疫治疗,应研究单克隆抗体在荷瘤小鼠中的特异性蓄积情况。我们研究了放射性标记的单克隆抗GD3抗体(IgM)在正常小鼠和携带人黑色素瘤异种移植物的裸鼠中的生物分布。在正常小鼠和移植黑色素瘤的小鼠中,肝脏、脾脏和肾脏中抗体的组织与血液分布比率均随时间增加,但在注射后5天内,其他正常组织未观察到明显变化。注射后4天和5天,观察到单克隆抗GD3抗体在移植的人黑色素瘤(HMV-II)中特异性蓄积。另一方面,在注射后5天的携带HMV-II异种移植物的小鼠中,未观察到标准鼠IgM在HMV-II组织中的特异性蓄积。由于给药后4天和5天,HMV-II组织中的分布组织与血液比率大于其他组织,因此免疫闪烁显像需要在给予单克隆抗GD3抗体4天后进行。在给予抗体4天后,也观察到单克隆抗GD3抗体在接种到小鼠体内的其他人类黑色素瘤(HMV-I、HMY-1和SK-MEL188)中的蓄积。本研究中使用的单克隆抗GD3抗体将有助于免疫检测或免疫治疗。

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