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通过在大鼠中联合使用冷L6单克隆抗体预负荷和随后的免疫吸附,增强125I标记的L6-生物素单克隆抗体(MAb)的放射免疫靶向作用。

Enhanced radioimmunotargeting of 125I-labeled L6-biotin monoclonal antibody (MAb) by combining preload of cold L6 MAb and subsequent immunoadsorption in rats.

作者信息

Garkavij M, Tennvall J, Strand S E, Norrgren K, Lindgren L, Nilsson R, Sjögren H O

机构信息

Department of Oncology, University Hospital, Lund, Sweden.

出版信息

Cancer Res. 1995 Dec 1;55(23 Suppl):5874s-5880s.

PMID:7493363
Abstract

The present study investigates whether tumor:normal tissue uptake ratios of radiolabeled monoclonal antibodies can be further improved by a combination of extracorporeal immunoadsorption (ECIA) and preload with unlabeled idiotypic monoclonal antibody. Athymic rats, heterotransplanted with human lung carcinoma under the kidney capsule (SR tumor) and i.m. (IM tumor), were divided into four study groups: controls, ECIA, preload, and combined preload+ECIA. The preload+ECIA procedure reduced the whole-body and plasma activity by 48 and 89%, respectively. After such combined procedure, the uptake of 125I-labeled L6-biotin in SR tumors was unchanged, while the uptake in normal tissues was considerably reduced. Tumor (T):bone marrow ratio was then increased by 17.5 times (after ECIA) and by 4.5 times (24 h after ECIA). Similar enhancements were achieved for T:liver and T:kidney ratios. For the IM tumors, the ratios were not as high as for SR tumors. The effects on T:normal ratios of preload+ECIA in combination were synergistic. The combined procedure resulted both in an increased uptake and prolonged persistence of 125I-labeled L6-biotin in the SR tumors and also in a reduction of corresponding uptake values in organs critical for radiation.

摘要

本研究调查了放射性标记单克隆抗体的肿瘤与正常组织摄取率是否能通过体外免疫吸附(ECIA)与未标记的独特型单克隆抗体预负荷相结合的方法得到进一步提高。将在肾包膜下异种移植人肺癌(SR肿瘤)和肌肉内移植人肺癌(IM肿瘤)的无胸腺大鼠分为四个研究组:对照组、ECIA组、预负荷组和预负荷+ECIA联合组。预负荷+ECIA程序分别使全身和血浆活性降低了48%和89%。经过这种联合程序后,SR肿瘤中125I标记的L6-生物素的摄取没有变化,而正常组织中的摄取则显著降低。肿瘤(T)与骨髓的比率随后增加了17.5倍(ECIA后)和4.5倍(ECIA后24小时)。T与肝脏和T与肾脏的比率也有类似的提高。对于IM肿瘤,这些比率不如SR肿瘤高。预负荷+ECIA联合对T与正常组织比率的影响具有协同作用。联合程序既导致125I标记的L6-生物素在SR肿瘤中的摄取增加和持续时间延长,也导致对辐射至关重要的器官中的相应摄取值降低。

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