摘要
目的 探讨^99Tc^m-膜联蛋白V（Annexin V）显像联合磁共振弥散加权成像（MR-DWI）非创伤性活体检测^125I粒子植入内照射致肺腺癌裸鼠移植瘤细胞凋亡的可行性.方法 将25只A549肺腺癌细胞皮下种植的BALB/c-nu裸鼠模型按随机数字表法分为实验组（n=13）和对照组（n=12）.实验组进行^125I粒子[表观活度为（24.8±6.3）MBq/粒]植入,对照组进行无活度的“冷粒子”植入,7～10d后进行^99Tc^m-Annexin V细胞凋亡显像,并同期行MR-DWI,然后处死裸鼠,取瘤体标本进行原位末端标记法（TUNEL）荧光免疫细胞凋亡检测及Survivin免疫组织化学检测.采用两独立样本t检验、χ^2检验和Pearson相关分析进行数据分析.结果 （1）实验组^99Tc^m-Annexin V细胞凋亡显像阳性率为69.2％（9/13）,大于对照组的8.3％（1/12,χ^2=12.73,P＜0.01）;（2）实验组瘤体^99Tc^m-Annexin V摄取比值、表观弥散系数（ADC）和细胞凋亡指数（AI）分别为2.91±0.85、（2.03±0.44）×10^-3 mm^2/s和（49±18）％,对照组相应指标分别为1.26±0.37,（1.29±0.21）×10^-3 mm^2/s和（11±4）％,实验组较对照组高（t=5.930、5.452和7.606,均P＜0.05）,而对照组的Survivin阳性表达率高于实验组[（46±13）％和（15±7）％,t=5.158,P＜0.05];（3）ADC、AI和瘤体摄取比值间两两相关（r分别为0.756、0.788和0.754,均P＜0.05）,Survivin表达与AI呈负相关（r=-0.772,P＜0.05）.结论 Survivin表达下调致细胞凋亡可能是^125I内照射治疗A549肺腺癌裸鼠移植瘤的机制之一;^99Tc^m-Annexin V显像联合MR-DWI能有效地对移植瘤细胞凋亡情况进行非创伤性活体检测,有利于^125I粒子内照射治疗早期疗效的判断.
Objective To detect apoptosis of transplanted lung adenocarcinoma cells in nude mice after ^125I brachytherapy by ^99Tc^m-Annexin V combined with diffusion weighted MRI （MR-DWI）.Methods Twenty-five BALB/c-nu nude mice models subcutaneously transplanted with A549 cells were divided into experimental group （EG,n=13） and control group （CG,n=12） by random number table method.One ^125I seed with apparent activity of （24.8±6.3） MBq was implanted into each mouse in EG,while CG underwent cold seed implantation.Both of ^99Tc^m-Annexin V imaging and MR-DWI were performed within 7-10 d after brachytherapy,then all mice were sacrificed and tumor cell apoptosis was detected by terminal oxynucleotidyl transferase mediated dUTP biotin nick end labeling （TUNEL） immunofluorescence,Survivin expression was assayed by SP.Two-sample t test,χ^2 test and Pearson correlation analysis were used for data analysis.Results Positive rate of cell apoptosis by ^99Tc^m-Annexin V imaging was 69.2%（9/13） and 8.3%（1/12） respectively in EG and CG （χ^2 =12.73,P〈0.01）.The uptake ratio of ^99Tc^m-Annexin V,apparent diffusion coefficient（ADC） value and apoptosis index（M） of the tumor in EG were 2.91±0.85,（2.03±0.44）×10^-3 mm^2/s and （49± 18） %,respectively,which were significantly higher than those of CG （1.26 ± 0.37,（1.29 ± 0.21） ×10^-3 mm^2/s and （11±4）% respectively,t=5.930,5.452,7.606,all P〈0.05）.Survivin expression in EG and CG was （46± 13） % and （15±7） % respectively （t =5.158,P〈0.05）.The value of ADC was correlated with AI and uptake ratio（r=0.756,0.788,both P〈0.05）.Uptake ratio was correlated with AI （r=0.754,P〈0.05）,while Survivin expression was negatively correlated with AI （r =-0.772,P〈0.05）.Conclusions Down-regulation of Survivin expression may play an important role in apoptosis induced by ^125I brachytherapy.^99Tc^m-Annexin V combined with MR-DWI could effectively evaluate apoptosis of lung adenocarcinoma cells in a non-invasive wa
出处
《中华核医学与分子影像杂志》
CSCD
北大核心
2014年第5期385-389,共5页
Chinese Journal of Nuclear Medicine and Molecular Imaging
关键词
肺肿瘤
肿瘤移植
细胞凋亡
放射疗法
碘放射性同位素
磁共振成像
膜联蛋白V
Lung neoplasms
Neoplasm transplantation
Cell apoptosis
Radiotherapy
Iodine radioisotopes
Magnetic resonance imaging
Annexin V
