The localisation of radiolabelled murine monoclonal antibody 81C6 and its Fab fragment in human glioma xenografts in athymic mice.

The localisation of radiolabelled murine monoclonal antibody 81C6 and its Fab fragment in human glioma xenografts in athymic mice.
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DOI:
10.3109/02688698808992668
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发表时间:
1988-01-01
影响因子:
1.1
通讯作者:
Bigner, D D
Bigner, D D
中科院分区:
医学4区
文献类型:
--
作者:
Colapinto, E V;Lee, Y S;Bigner, D D

文献摘要

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放射性碘标记的Fab片段的单克隆抗体(单克隆抗体)81 C6,与胶质瘤相关的细胞外基质抗原反应,在无胸腺小鼠皮下和颅内异种移植的D-54 MG胶质瘤细胞的本地化进行了研究。与完整Mab 81 C6相比,体外81 C6 Fab显示出免疫反应性和抗原亲和力的显著丧失。在体内,81 C6 Fab的血浆半衰期为7.0小时,而81 C6为2.1天。肿瘤中的81 C6 Fab水平在2-6小时内达到峰值,为2.6-3.8%注射剂量/g; Mab 81 C6在48小时达到33.9%剂量/g。Mab 81 C6的定位指数和肿瘤:组织比为上级。131 I-81 C6 Fab对肿瘤和正常组织的估计辐射剂量低于131 I-81 C6。为了实现片段作为定位剂的理论益处,需要具有更高免疫反应性和亲和力的Fab片段或二价F(ab ')2片段。
The localisation of the radioiodinated Fab fragment of monoclonal antibody (Mab) 81C6, reactive with a glioma-associated extracellular matrix antigen, was studied in athymic mice bearing subcutaneous and intracranial xenografts of D-54 MG glioma cells. In vitro 81C6 Fab showed a marked loss of immunoreactivity and affinity for antigen compared to intact Mab 81C6. In vivo, the plasma half-life of 81C6 Fab was 7.0 hours compared to 2.1 days for 81C6. 81C6 Fab levels in tumours peaked at 2.6-3.8% injected dose/g in 2-6 h; Mab 81C6 reached 33.9% dose/g at 48 h. Localisation indices and tumour:tissue ratios were superior for Mab 81C6. Estimated radiation doses to tumour and normal tissues were lower for 131I-81C6 Fab than 131I-81C6. To realise the theoretical benefits of fragments as localising agents, Fab fragments of higher immunoreactivity and affinity, or bivalent F(ab')2 fragments are required.