^(211)At-单抗(3H11)对裸鼠载人胃癌肿瘤模型的治疗作用

THE RADIOIMMUNOTHERAPY EFFECT OF ASTATINE-211-LABELLED 3H11 AGAINST HUMAN GASTRIC CANCER IN IMPLANTED NUDE MICE MODEL

通过纯α放射性核素^(211)At与抗人胃癌鼠源单抗3H11的结合物对载人胃癌肿瘤裸鼠进行实验性治疗.实验结果表明,与PBS溶液相比,^(211)At—3H11显著抑制了移植瘤的生长;具靶特异性的3H11主要起导向作用,而^(211)At衰变放射的α粒子可引起靶组织细胞核变性、线粒体肿胀甚至破裂、溶酶体透性改变、瘤内毛细血管损伤,毛细血管损伤使靶组织缺氧,可加剧一系列酶组化特性改变,进而影响细胞的结构和功能状态。

Experimental radioimmunotherapy of astatine-211 - labelled 3H11(a murine anti-human gastric cancer monoclonal antibody) were studied in implanted nude mice model. The enzyme histochemical and ultrastructural alterations of the target tissue cells induced by an i. v. injection to models were also reported in order to gain some insight into the effect, mechanism of 211At-3H11. The results are as follow:(1)The combination,211At-3H11 (8uCi a mouse) shows specifically inhibition to the growth of the heterograft tumor. On the 9th day after administration,compared with PBS,its rate of tumor-growing inhibition came up to 70%(P<0. 005).(2)211At - 3H11 induced the variations of target tissue in enzyme histochemistry and ultrastructure. After administration for 15-16h,it was found that the activities of enzymes locating in lysosome (ACP) and cytosol (LDH) were increased, the others locating in mitochondria (NADH,NADPH,MDH,CCO) and in endocuticle of capillary in the heterograft (ATPase) were decreased. And there was a marked degree of injury to the tumor cell as evidenced by a swelling of mitochondria in various degree,irregular denaturation of nuclei with an aggregation or reduction of chromatin,et al. The blood capillaries in the tumor were in juried also. Those are suggested that the mechanism of functional damage to target cells induced by 211At-3H11 is mainly due to the injury of astatine- 211 emission to the cells and the blood capillary of the tumor; 3H11 guides the combination to the target tissue.(3)211At-3H11 also injuried the thyroid in some degree.