体外免疫吸附柱在放射免疫治疗中的作用

发布时间：2018-05-30 19:48

本文选题：体外 + 免疫吸附柱　；参考：《中南大学》2005年博士论文

【摘要】：体外免疫吸附柱(ECAT)是通过将人体血液引至体外循环,通过各种不同的吸附柱,选择性清除血浆中过剩的放射性核素与单克隆抗体(单抗,MAbs)的螯合物(chelate)从而降低放射敏感脏器中放射性活度的一种新方法。通过使用体外免疫吸附柱,肿瘤与正常组织(T/N)的治疗比可以提高,更高剂量的螯合物可以注射到体内,从而达到杀灭肿瘤的目的。论文1:通过腹腔给药的途径注射~(111)In-HMFG_1-生物素(biotin)后观察体外免疫吸附柱能否降低大鼠体内放射性活度;并对生物素化的~(111)In-HMFG_1以及非生物素化的~(111)In-HMFG_1进行药代动力学(PK)分布的比较。研究结果显示,实施体外免疫吸附后,大鼠全身及血中放射性活度分别下降了35-40%(p0.05)和75-86%(p0.01);放射敏感脏器中放射性活度也有显着性地降低。论文2:使用体外免疫吸附柱之前,首先必须决定最佳实施时间,而单抗的血药代动力在决定最佳时间上起着至关重要的作用。本研究观察了动物体内静脉注射不同单抗结合“1033”以及~(111)In后其血药代是否有显着性差异。如果没有显着性差异的话,可用一种单抗的血药代来代替其它单抗的血药代,这样即可以节约时间,有不需对每一个单抗都做耗时耗力的血药代研究。实验中发现三种结合“1033”以及~(111)In的人鼠嵌合型或人源化单抗((rituximab,trastuzumab,BR96)的血药代没有显着性差异,且全身及脏器中的放射性活度也相似。但结合有另一种螯合剂的单抗(hMN14)的血、全身及脏器中的放射性活度显示了明显的不同:血及全身放射性活度下降较快,肝中的放射性活度较高。这表明可用一种单抗的血药代来代替其它单抗的血药代来决定体外免疫吸附柱的最佳实施时间只要结合相同的螯合剂“1033”以及相同的核
[Abstract]:The extracorporeal immunosorbent column (ECAT) is by diverting human blood to cardiopulmonary bypass through various adsorption columns. A new method for selectively removing excess radionuclides from plasma and chelate of monoclonal antibodies (MAbs) to reduce radioactivity in radiosensitive organs. By using an in vitro immunosorbent column, the treatment ratio of tumor to normal tissue T / N can be increased, and a higher dose of chelate can be injected into the body to kill the tumor. Paper 1: the pharmacokinetics of biotin was compared between the biotin (111In-HMFG1-1) and the biotin (111In-HMFG1) after intraperitoneal administration, and the pharmacokinetics of biotinylated In-HMFG1 was compared with that of non-biotin (111In-HMFG1) after the in vitro immunosorbent column could decrease the radioactivity in rats. The results showed that the radioactivity of whole body and blood decreased 35-40% and 75-86%, respectively, and the radioactivity of radiosensitive viscera decreased significantly after in vitro immunosorbent. Paper 2: before using an in vitro immunosorbent column, the optimal implementation time must be determined, and the pharmacokinetics of the monoclonal antibody plays an important role in determining the optimal time. In this study, we observed whether there were significant differences in the blood pharmacokinetics of different monoclonal antibodies ("1033") after intravenously injection of "1033" and 111terin. If there is no significant difference, one monoclonal antibody can be used to replace other monoclonal antibodies, which can save time and have no time consuming blood pharmacokinetic research for each monoclonal antibody. It was found that there was no significant difference in the blood pharmacokinetics of the three human mouse chimeric or humanized monoclonal antibodies ("1033" and "1033"), and the radioactivity in the whole body and organs were similar. However, the radioactivity in the whole body and in the viscera showed obvious difference in the blood combined with another kind of chelating agent hMN14: the radioactivity of the blood and the whole body decreased more quickly, and the activity of the liver was higher. This suggests that one monoclonal antibody can be used instead of the other monoclonal antibody to determine the optimal time for the in vitro immunosorbent column as long as it binds to the same chelating agent "1033" and the same nucleus.
【学位授予单位】：中南大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R392

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