摘要
目的探讨^(90)Y-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-酪氨酸3-奥曲肽(DOTATOC)对人胰腺神经内分泌瘤细胞BON-1的抑制作用。方法(1)采用^(90)Y对DOTATOC进行标记,然后纯化^(90)Y-DOTATOC;(2)考察^(90)Y-DOTATOC的体外稳定性;(3)采用噻唑蓝(MTT)法,分别考察^(90)Y、DOTATOC、^(90)Y-DOTATOC对人胰腺神经内分泌瘤细胞BON-1和人胰腺胆管瘤细胞PANC-1的抑制作用,并分别计算细胞增殖抑制率。设立阴性对照组、阳性对照组(长春新碱,50μmol/L)、DOTATOC组(25μmol/L)、^(90)Y组(1.8 MBq/ml)、^(90)Y-DOTATOC高剂量组(^(90)Y的放射性浓度为1.8 MBq/ml,DOTATOC的浓度为25μmol/L)、^(90)Y-DOTATOC中剂量组(^(90)Y的放射性浓度为0.37 MBq/ml,DOTATOC的浓度为25μmol/L)、^(90)Y-DOTATOC低剂量组(^(90)Y的放射性浓度为0.074 MBq/ml,DOTATOC的浓度为25μmol/L)。组间比较采用独立样本t检验。结果(1)^(90)Y标记DOTATOC的标记率为(61.93±3.53)%,放射化学纯度为(98.88±0.38)%,放射性浓度为4.6 MBq/ml,比活度为1.6 GBq/μmol。(2)^(90)Y-DOTATOC在生理盐水和10%胎牛血清中放置7 d后的放射化学纯度分别为97.73%和97.02%。(3)加药24、48 h后,与阴性对照组相比,DOTATOC组对BON-1细胞的抑制作用均显著增高,且差异有统计学意义(t=2.654,3.981,均P<0.05);加药24、48 h后,^(90)Y-DOTATOC高、中剂量组对BON-1和PANC-1细胞的抑制作用均优于DOTATOC组,且差异有统计学意义(t=2.267~3.852,均P<0.05);加药24、48 h后,^(90)Y组对PANC-1和BON-1细胞的抑制作用均明显低于^(90)Y-DOTATOC高剂量组,且差异有统计学意义(t=2.698~3.180,均P<0.05)。结论^(90)Y-DOTATOC对BON-1细胞有较强的抑制作用,且与^(90)Y的活度呈剂量依赖关系。与单独使用DOTATOC或者^(90)Y对比,^(90)Y-DOTATOC对BON-1细胞的抑制作用更强。
Objective To investigate the inhibitory effect of ^(90)Y-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Tyr(3)-octreotide(DOTATOC)on the human pancreatic neuroendocrine tumor cell line BON-1.Methods(1)DOTATOC was labeled with ^(90)Y,and then purified it.(2)The stability of ^(90)Y-DOTATOC was investigated in vitro.(3)The thiazole blue method was used to examine the inhibitory effects of ^(90)Y,DOTATOC,and ^(90)Y-DOTATOC on human pancreatic neuroendocrine tumor cell BON-1 and human pancreatic cholangioma cell PANC-1,and then the cell proliferation inhibition rate was calculated.Negative control group,positive control group(Vincristine,50μmol/L),DOTATOC group(25μmol/L),^(90)Y group(1.8 MBq/ml),^(90)Y-DOTATOC high-dose group(^(90)Y dose was 1.8 MBq/ml,DOTATOC concentration was 25μmol/L),^(90)Y-DOTATOC medium dose group(^(90)Y dose was 0.37 MBq/ml,DOTATOC concentration was 25μmol/L),^(90)Y-DOTATOC lowdose group(^(90)Y dose was 0.074 MBq/ml,DOTATOC concentration was 25μmol/L)were set up.Independent sample t-test was used for inter group comparison.Result(1)The labeling rate of the DOTATOC labeled with ^(90)Y was(61.93±3.53)%.Its radiochemical purity was(98.88±0.38)%,its radioactive concentration was 4.6 MBq/ml,and its specific activity was 1.6 GBq/μmol.(2)The radiochemical purity of ^(90)Y-DOTATOC after being placed in physiological saline and 10%bovine serum for 7 days was 97.73%and 97.02%,respectively.(3)After 24 h and 48 h of drug addition,the inhibitory effect of the DOTATOC group on BON-1 cells was significantly increased compared with that of the negative group,and the difference was statistically significant(t=2.654,3.981,all P<0.05).After 24 h and 48 h of drug addition,the inhibitory effects of the high and medium ^(90)Y-DOTATOC dose groups on BON-1 and PANC-1 cells were superior to that of the DOTATOC group,and the difference was statistically significant(t=2.267–3.852,all P<0.05).After 24 h and 48 h of drug addition,the inhibitory effects of the pure ^(90)Y group on PANC-1 and BON-1 cells
作者
王翰
邓启民
曾永龙
Wang Han;Deng Qimin;Zeng Yonglong(Department of Drug Research and Development,Chengdu Yunke Pharmaceutical Co.,Ltd,Chengdu 610225,China)
出处
《国际放射医学核医学杂志》
2023年第5期289-294,共6页
International Journal of Radiation Medicine and Nuclear Medicine
