摘要
目的 在前人工作的基础上，分别设计了内放疗和化疗靶向治疗药物——鼻咽癌单克隆抗体^188Re标记物^188Re鼻咽癌单克隆抗体（BAC5）]和BAC5与平阳霉素（PYM）的耦联物（PYM-BAC5），观察了两药联合使用对体外培养的鼻咽癌细胞（CNE2）的抑制作用。方法直接法标记^188Re-BAC5以SnCl2、2-巯基乙醇（2-ME）和柠檬酸-酒石酸作还原剂和耦联剂，葡聚糖T-40被氧化成多醛基葡聚糖（PAD）用以耦联PYM和BAC5。四甲基偶氮唑蓝（MTr）法检测2种抗肿瘤药物对体外培养CNE2的抑制作用，并以^188ReO4-、188Re-mlgG和PYM为对照组，生理盐水为空白对照组。结果^188Re-BAC5标记率为92％～95％，放射性浓度为5254kBq／ml；PYM．BAC，中m（PYM）：m（BAC，）=1：0．526，n（PYM）：n（BAC5）=1：51。2种药单独治疗组、联合治疗组及各自对照组的抑制效应都呈明显的剂量-效应关系。但^188Re-BAC5，对CNE2的抑制作用随放射性浓度的增加而增加，半数抑制浓度（Ic50）为264kBq／ml，抑制作用明显强于^188ReO4^-（IC50=882kSq／m1）和^188Re-mIgG（IC50=1062kSq／ml）组。PYM-BAC5的IC50为10．07μg／ml，而单纯PYM的IC50为63．60μg／ml；合用药中^188Re-BAC5的IC50为32．1kBq／ml，PYM-BAC5的IC50为1．70μg／ml，分别明显小于2种药单用时各自的IC50，以上各组差异均有统计学意义（t=22．62和37．70，P〈0．01）。结论靶向治疗组（^188Re-BAC5）抑瘤效果明显好于非靶向组；联合靶向治疗组（^188Re-BAC5＋PYM-BAC5）的抑瘤效果明显好于单独用药组。
Objective Combination of radiation and chemical agents was supposed to have better effect on nasopharyngeal cancer. This study compared the in vitro inhibiting effects of ^188Re-monoclonal antibody （ BAC5 ） with or without pingyangmycin conjugated BAC5 （ PYM-BAC5 ） on nasopharyngeal carcinoma cells （CNE2）. Methods ^188Re-BAC5 was prepared using 2-mercaptoethanol （ ME）, citric acid and tartaric acid as reducing and transchelation agents. Oxidized dextran T-40 （polyaldehyde dextran, PAD） was used to conjugate PYM to BACs. 3- （4, 5-dimethylthiazol-2-y1） -2, 5-diphenylte-trazolium bromide （MTr） method was applied to assess anti-tumor effects of ^188Re-BAC5 and PYM-BAC5 on CNE2 cells. Results The labeling efficiency of ^188Re-BAC5 was 92%～95% with a radioactive concentration of 5254 kBq/ml. The composition of PYM-BAC5 was m （ PYM ） ： m （ BAC5 ） = 1 ： 0. 526, or n （ PYM ） ： n （ BAC5 ） = 1 ： 51. The inhibition effects of each treatment regime were in a dose dependent manner. The 50% inhibition doses （IC59） of ^188Re-BAC5, ^188Re-mIgG and ^188ReO4- were 264, 1062 and 882 kBq/ml, respectively. The ICso of the PYM-BAC5 and free PYM were 10.07 and 63.60 μg/ml, respectively. Combining ^188Re-BAC5 and PYM-BAC5 reduced the ICso of ^188Re-BAC5 and PYM-BAC5 down to 32.1 kBq/ml and 1.70 μg/ml. Conclusions It was proved that targeted therapy had better anti-tumor effect. The combination of targeted radiation and chemical agents （ ^188Re-BAC5 ＋ PYM-BAC5 ） obtained the best therapeutic effect on cultured CNE2 cells.
出处
《中华核医学杂志》
CAS
CSCD
北大核心
2008年第1期31-34,共4页
Chinese Journal of Nuclear Medicine
基金
国家自然科学基金（30070231）
关键词
鼻咽肿瘤
抗体
单克隆
铼
平阳霉素
综合疗法
体外研究
Nasopharyngeal neoplasms
Antibodies, monoclonal
Rhenium
Pingyangmycin
Combined modality therapy
In vitro
