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完整A7单克隆抗体与F(ab')2片段用于裸鼠人结肠癌放射免疫显像的比较研究。

Comparative study of intact A7 MoAb and F(ab')2 fragments for radioimmunoimaging of human colon cancer in nude mice.

作者信息

Kojima S, Suzuki N, Shimura N, Kubodera A, Kubota K, Yamaguchi T, Takahashi T, Oyamada H

机构信息

Research Institute for Biosciences, Science University of Tokyo, Chiba, Japan.

出版信息

Nucl Med Biol. 1993 Apr;20(3):243-8. doi: 10.1016/0969-8051(93)90044-u.

Abstract

Differences of pharmacokinetics and tumor imaging ability between intact monoclonal antibody A7 (A7 MoAb) and F(ab')2 fragments were studied in human colon cancer (LS-174T)-bearing nude mouse. First of all, we examined the yield and the immunoreactivity of F(ab')2 fragments after treatment with ficin as a function of time. The yield of F(ab')2 fragments reached about 50% after ficin treatment for 8 h, and the F(ab')2 retained about 80% of the immunoreactivity of the corresponding MoAb. Longer digestion with ficin produced smaller fragments (less than 92 kDa) with a lower yield and most of the immunoreactivity was lost. In pharmacokinetics studies, the F(ab')2 was preferentially taken up by the tumor, was cleared more rapidly from the blood circulation and seemed to have less non-specific tissue binding than intact A7 MoAb. In addition, the tumor image obtained at an early time using 131I-F(ab')2 was much superior in quality to that with intact 131I-A7 MoAb. The use of F(ab')2 fragments may be effective for tumor diagnosis and therapy.

摘要

在荷人结肠癌(LS-174T)裸鼠中研究了完整单克隆抗体A7(A7单克隆抗体)与F(ab')2片段之间的药代动力学差异及肿瘤成像能力。首先,我们检测了用无花果蛋白酶处理后F(ab')2片段的产量和免疫反应性随时间的变化。用无花果蛋白酶处理8小时后,F(ab')2片段的产量达到约50%,且F(ab')2保留了相应单克隆抗体约80%的免疫反应性。用无花果蛋白酶进行更长时间的消化会产生更小的片段(小于92 kDa),产量更低,且大部分免疫反应性丧失。在药代动力学研究中,F(ab')2优先被肿瘤摄取,从血液循环中清除得更快,并且似乎比完整的A7单克隆抗体具有更少的非特异性组织结合。此外,使用131I-F(ab')2在早期获得的肿瘤图像质量比完整的131I-A7单克隆抗体的图像质量要好得多。F(ab')2片段的使用可能对肿瘤诊断和治疗有效。

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