MR扩散加权成像在体评估人钠碘转运体转染鼻咽癌介导^131I治疗效果的实验研究

Evaluation of therapy effect of ^131I treatment of nasopharyngeal carcinoma xenograft mediated by hNIS gene transfection in vivo using diffusion weighted MR

目的探讨人钠碘转运体（hNIS）转染鼻咽癌移植瘤^131I治疗后的DWI特征及肿瘤细胞凋亡和增殖的情况。方法利用转染hNIS的鼻咽癌细胞株CNE-2-hNIS细胞（实验组）和未转染hNIS的CNE-2细胞（对照组）分别建立荷鼻咽癌裸鼠模型，腹膜内注射^131I，MR观察实验组和对照组移植瘤在^131I治疗后3、6、12、18、24d的体积、ADC值的变化，将ADC值与治疗后6、12、18、24d细胞凋亡情况以及半胱氨酸蛋白酶-3（Caspase-3）和增殖指标（Ki-67）的表达情况进行相关性分析。2组间均数比较采用独立样本t检验，相关分析采用Pearson直线相关分析。结果^131I治疗后实验组移植瘤体积较对照组明显缩小（t值为8．27～19．46，P〈0．05）。^131I治疗后第3天，实验组ADC值有增高，第6天和第12天达到高峰，随后ADC值下降。治疗后移植瘤ADC值与细胞凋亡率呈正相关（r=0．72，P〈0．05），与Caspase-3阳性率呈正相关（r=0．65，P〈0．05），与Ki-67标记指数呈负相关（r=-0．71，P〈0．05）。结论ADC值可以反映^131I对hNIS转染鼻咽癌移植瘤生长的抑制情况，DW-MRI技术在早期无创性监测^131I靶向治疗hNIS转染鼻咽癌移植瘤的治疗效果方面具有可能性。

Objective To investigate the imaging characteristic of DWI, tumor cell apoptosis and proliferation of nasopharyngeal carcinoma （NPC） xenograft transfected hNIS gene after 131I treatment. Methods The NPC xenograft models were established with CNE-2-hNIS cells （experimental group） and CNE-2 cells（ control group） respectively. After i.p. injections 131I in the experimental group and control group, the changes of xenograft tumor volume and ADC value were observed in 3, 6, 12, 18, 24 days by MR scan. The correlations of changes of ADC with pathological TUNEL, Caspase-3 immunohistochemistry of apoptosis, and Ki-67 proliferation detection were further investigated. Independent samples t-test were compared between the two groups and Pearson linear correlation analysis was used. Results The tumor volume of the experimental group was significantly reduced compared with that of the control group after 131I treatment （t values ： 8.27-19.46, P 〈 0. 05）. DW-MRI showed that in the 3th day after 131 I treatment, ADC values increased in the experimental group, and ADC values reached the peak in the 6th and 12th day after 131I treatment, then ADC values were decreased. ADC values after treatment was positively correlated with apoptotic index （r =0. 72,P 〈0.05） and caspase-3 positive rate （r =0. 65,P 〈0. 05） and there was a negative correlation with Ki-67 proliferation index （r = - 0. 71, P 〈 0. 05 ）. Conclusion ADC values can reflect growth inhibition of NPC xenograft transfected hNIS gene after 131I treatment. It is possible that DWMRI techniques can be used in early non-invasively monitor the therapy effect of 131I treatment of NPC xenografts transfected hNIS gene.