Detection of cell apoptosis induced by 125I brachytherapy in nude mice bearing lung adenocarcinoma using 99Tcm-Annexin V imaging combined with diffusion weighted MRI / 中华核医学与分子影像杂志

ABSTRACT

Objective To detect apoptosis of transplanted lung adenocarcinoma cells in nude mice after 125I brachytherapy by 99Tcm-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 99Tcm-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,x2 test and Pearson correlation analysis were used for data analysis.Results Positive rate of cell apoptosis by 99Tcm-Annexin V imaging was 69.2％(9/13) and 8.3％(1/12) respectively in EG and CG (x2 =12.73,P＜0.01).The uptake ratio of 99Tcm-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 mm2/s and (49± 18) ％,respectively,which were significantly higher than those of CG (1.26 ± 0.37,(1.29 ± 0.21) ×10-3 mm2/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.99Tcm-Annexin V combined with MR-DWI could effectively evaluate apoptosis of lung adenocarcinoma cells in a non-invasive way,thus it might be helpful in evaluation of early efficacy of 125I brachytherapy.