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免疫球蛋白M单克隆抗体及其片段在荷白血病肿瘤小鼠体内的时间进程定位

Time course localization of immunoglobulin M monoclonal antibody and its fragments in leukemic tumor-bearing mice.

作者信息

Maillet T, Roche A C, Thérain F, Monsigny M

出版信息

Cancer Immunol Immunother. 1985;19(3):177-82. doi: 10.1007/BF00199223.

Abstract

In vivo localization of a mouse monoclonal antibody (F2-10.23 IgM) binding leukemic L 1210 cells was studied in DBA/2 mice bearing an L 1210 tumor. F(ab')2 fragments were prepared and their specific binding to L 1210 cells was analyzed by flow cytofluorometry. Radio-localization studies were performed by using 125I- or 131I-labeled IgM monoclonal antibody or its F(ab')2 fragments to ascertain their capacity to visualize the L 1210 tumor. F(ab')2 fragments were cleared more rapidly than the whole IgM; the clearance was as fast in healthy as in tumor-bearing mice. The tumor-to-muscle ratio observed 24 h after injection of 125I-radiolabeled F(ab')2 fragments and 125I-radiolabeled IgM was 10; the radioactivity level in the blood with F(ab')2 fragments was lower than with IgM, and so gamma-camera imaging was workable with F(ab')2 fragments without background subtraction. The tumor localization was studied over a period of 5 days by recording the distribution of the iodinated fragments in the tumor-bearing leg compared with that in the normal leg, and by computer analysis of the region of interest. F(ab')2 fragments gave better results than intact IgM in tumor visualization. Nevertheless, the rapid clearance of this antibody or its F(ab')2 fragments make them hardly suitable as carriers of toxic drugs.

摘要

在患有L 1210肿瘤的DBA/2小鼠中,研究了一种与白血病L 1210细胞结合的小鼠单克隆抗体(F2-10.23 IgM)的体内定位。制备了F(ab')2片段,并通过流式细胞荧光术分析了它们与L 1210细胞的特异性结合。通过使用125I或131I标记的IgM单克隆抗体或其F(ab')2片段进行放射性定位研究,以确定它们可视化L 1210肿瘤的能力。F(ab')2片段的清除速度比完整的IgM更快;在健康小鼠和荷瘤小鼠中清除速度一样快。注射125I放射性标记的F(ab')2片段和125I放射性标记的IgM后24小时观察到的肿瘤与肌肉的比率为10;F(ab')2片段组血液中的放射性水平低于IgM组,因此F(ab')2片段无需进行背景扣除即可用γ相机成像。通过记录荷瘤腿与正常腿中碘化片段的分布,并通过感兴趣区域的计算机分析,在5天的时间内研究了肿瘤定位。在肿瘤可视化方面,F(ab')2片段比完整的IgM产生更好的结果。然而,这种抗体或其F(ab')2片段的快速清除使得它们几乎不适合作为有毒药物的载体。

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Monoclonal antibody (IgM) specific to mouse lymphoma cells (L 1210): isolation and therapeutic properties.
Cell Biol Int Rep. 1982 Jun;6(6):557-65. doi: 10.1016/0309-1651(82)90179-5.

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