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两种抗人B细胞慢性淋巴细胞白血病单克隆抗体及其F(ab)'2片段在异种移植模型中的药代动力学、生物分布和肿瘤定位

Pharmacokinetics, biodistribution and tumor localization of two anti-human B-cell chronic lymphocytic leukemia monoclonal antibodies and their F(ab)'2 fragments in a xenograft model.

作者信息

Zhu Z, Ghose T, Iles S, Yang C, Lee S H, Fernandez L A, Lee C L

机构信息

Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.

出版信息

Cancer Lett. 1994 Jan 15;76(1):31-44. doi: 10.1016/0304-3835(94)90131-7.

DOI:10.1016/0304-3835(94)90131-7
PMID:8124664
Abstract

We investigated the pharmacokinetics, biodistribution and tumor localization of intravenously injected Dal B01 and Dal B02, two monoclonal antibodies (MoAbs) directed against tumor associated antigens on human chronic lymphocytic leukemia (CLL) B cells, and their F(ab)'2 fragments in nude mice bearing xenografts of the human B cell CLL line D10-1. More of the percentages of the injected dose (% ID) of these two MoAbs and their F(ab)'2 fragments specifically localized in the tumor xenografts than in normal tissues. Compared to intact MoAbs, their F(ab)'2 fragments had lower % ID in tumors and were cleared from circulation faster. Well-defined tumor images were obtained at 24 and 48 h after administration of [131I]Dal B02 F(ab)'2 fragment and at 96-192 h after administration of [131I]Dal B02. A comparison between intravenous and intraperitoneal routes of administration of [131I]Dal B02 did not reveal any difference in the localization of % ID in tumor or normal tissues.

摘要

我们研究了静脉注射Dal B01和Dal B02这两种针对人慢性淋巴细胞白血病(CLL)B细胞上肿瘤相关抗原的单克隆抗体(MoAbs)及其F(ab)'2片段在携带人B细胞CLL细胞系D10-1异种移植瘤的裸鼠体内的药代动力学、生物分布和肿瘤定位情况。与正常组织相比,这两种单克隆抗体及其F(ab)'2片段的注射剂量百分比(% ID)更多地特异性定位于肿瘤异种移植瘤中。与完整的单克隆抗体相比,它们的F(ab)'2片段在肿瘤中的% ID较低,且从循环中清除得更快。在注射[131I]Dal B02 F(ab)'2片段后24小时和48小时以及注射[131I]Dal B02后96 - 192小时获得了清晰的肿瘤图像。[131I]Dal B02静脉注射和腹腔注射途径之间的比较未显示肿瘤或正常组织中% ID定位存在任何差异。

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