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辅助性131I-抗癌胚抗原抗体放射免疫疗法可抑制实验性结肠癌肝转移的发展。

Adjuvant 131I-anti-CEA-antibody radioimmunotherapy inhibits the development of experimental colonic carcinoma liver metastases.

作者信息

Mahteme H, Lövqvist A, Graf W, Lundqvist H, Carlsson J, Sundin A

机构信息

Department of Surgery, Uppsala University, Sweden.

出版信息

Anticancer Res. 1998 Mar-Apr;18(2A):843-8.

PMID:9615730
Abstract

Adjuvant radioimmunotherapy (RIT) for human colonic cancer was performed in a nude rat model of experimental liver metastases. Thirty-three rats were injected intraportally through a mesenteric vein with 5 x 10(6) cells from the human colonic cancer cell line LS174T. Within half an hour, 20 MBq (n = 2), 75 MBq (n = 5), or 150 MBq (n = 10) of the 131I-labelled anti- carcinoembryonic antigen (CEA) monoclonal antibody (MAb) 38S1 was administered intravenously (i.v.), whereas control groups received either i.v. saline injections (n = 12) or 150 MBq of the irrelevant 131I-labelled MAb 79C (n = 4). Decay corrected whole-body data showed that more than 80% of the initially MAb-bound radioiodine was excreted during the first 2 weeks. Whole- body clearance and blood clearance of 131I-38S1 and 131I-79C were essentially similar. At sacrifice 5-7 weeks after administration, neither 20 MBq nor 75MBq 131I-38S1 significantly prevented the development of liver metastases. By contrast, with 150 MBq, no metastases formed in the animals treated with MAb 131I-38S1 or 131I-79C. A radiation induced effect on the haematopoietic system was found in the 150MBq dosage groups. It is concluded that the inhibition of tumour induction was not strictly dependent on a radiation dose delivered by a tumour-specific MAb. Since a non-tumour-specific 131I-MAb, in a smaller group of animals, proved equally efficacious in preventing tumour growth, the total body 131I dose was probably the major contributing factor.

摘要

在裸鼠实验性肝转移模型中进行了人结肠癌辅助放射免疫疗法(RIT)。33只大鼠通过肠系膜静脉经门静脉注射5×10⁶个人结肠癌细胞系LS174T的细胞。半小时内,静脉注射(i.v.)20MBq(n = 2)、75MBq(n = 5)或150MBq(n = 10)的¹³¹I标记的抗癌胚抗原(CEA)单克隆抗体(MAb)38S1,而对照组接受静脉注射生理盐水(n = 12)或150MBq不相关的¹³¹I标记的MAb 79C(n = 4)。衰变校正后的全身数据显示,最初与单克隆抗体结合的放射性碘超过80%在最初2周内排出。¹³¹I - 38S1和¹³¹I - 79C的全身清除率和血液清除率基本相似。给药后5 - 7周处死时,20MBq和75MBq的¹³¹I - 38S1均未显著阻止肝转移的发生。相比之下,150MBq时,用MAb 131I - 38S1或131I - 79C治疗的动物未形成转移灶。在150MBq剂量组中发现了辐射对造血系统的影响。得出的结论是,肿瘤诱导的抑制并不严格依赖于肿瘤特异性单克隆抗体传递的辐射剂量。由于在较小的动物组中,一种非肿瘤特异性的¹³¹I - MAb在预防肿瘤生长方面同样有效,全身¹³¹I剂量可能是主要的促成因素。

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