摘要目的:探讨3′－脱氧－3′－ 18F－氟胸苷(FLT) microPET/CT显像评价沉默乳腺癌易感基因1(shBRCA1)表达对MDA－MB－231乳腺癌裸鼠模型的放疗增敏作用。 方法:将24只BALB/c裸鼠按随机数字表法分为4组(每组6只)，分别为阴性对照(NC)组、NC+放疗组、shBRCA1组、shBRCA1+放疗组，分别于放疗前和4次放疗结束后24 h对裸鼠行 18F－FLT microPET/CT显像。比较4组肿瘤治疗前后SUV max的变化，并分析治疗后各组肿瘤总增殖体积(TPV)。免疫组织化学法分析肿瘤组织细胞增殖核抗原Ki－67的表达情况。采用配对 t检验、单因素方差分析、最小显著差异 t检验和Pearson相关分析数据。 结果:成功构建了靶向BRCA1的乳腺癌细胞。放疗前，NC组、NC+放疗组、shBRCA1组和shBRCA1+放疗组的SUV max分别为1.034±0.137、1.031±0.152、1.028±0.169和1.026±0.156，差异无统计学意义( F＝0.00， P＝0.999)；4次放疗结束后24 h，4组的SUV max分别为1.367±0.100、0.781±0.079、1.306±0.213和0.597±0.129，差异有统计学意义( F＝44.77， P<0.001)，其中shBRCA1+放疗组的SUV max较NC+放疗组更低( t＝2.98， P＝0.014)；NC+放疗组和shBRCA1+放疗组的SUV max均较治疗前降低( t值：5.82、5.44， P值：0.002、0.003)，NC组和shBRCA1组的SUV max则均较治疗前增加( t值：－4.47、－3.98， P值：0.007、0.011)。shBRCA1+放疗组较NC+放疗组相比TPV更小(0.48±0.03和0.61±0.07； F＝25.36， t＝3.82， P＝0.003)。Ki－67在shBRCA1+放疗组中表达少于NC+放疗组(0.286±0.072和0.476±0.093； F＝15.73， t＝3.61， P＝0.007)。Ki－67表达与SUV max呈正相关( r＝0.83， P<0.001)。 结论:18F－FLT microPET/CT显像可以评价shBRCA1表达对MDA－MB－231乳腺癌裸鼠模型的放疗增敏作用。

abstractsObjective:To investigate the radiosensitizing effect of silencing breast cancer susceptibility gene 1 (shBRCA1) expression on MDA-MB-231 breast cancer bearing nude mice by 3′-deoxy-3′- 18F-fluorothymidine ( 18F-FLT) microPET/CT imaging. Methods:Twenty-four BALB/c nude mice were divided into 4 groups ( n=6 in each group) according to the random number table method, namely negative control (NC) group, NC+ radiotherapy group, shBRCA1 group and shBRCA1+ radiotherapy group. 18F-FLT microPET/CT imaging was performed before and 24 h after radiotherapy. The changes of SUV max before and after radiotherapy were compared among 4 groups, and the total proliferative volume (TPV) of tumors in each group after treatment was also analyzed. The expression of Ki-67 in tumor tissues was analyzed by immunohistochemistry. Data were analyzed by paired t test, one-way analysis of variance, least significant difference t test and Pearson correlation analysis. Results:Breast cancer cells targeting the BRCA1 were constructed. Before radiotherapy, the differences of SUV max among the NC group, NC+ radiotherapy group, shBRCA1 group and shBRCA1+ radiotherapy group were not statistically significant (1.034±0.137, 1.031±0.152, 1.028±0.169 and 1.026±0.156; F=0.00, P=0.999). Twenty-four hours after the end of the four times of radiotherapy, the differences of SUV max among the 4 groups were statistically significant (1.367±0.100, 0.781±0.079, 1.306±0.213 and 0.597±0.129; F=44.77, P<0.001), with lower SUV max in the shBRCA1+ radiotherapy group compared with the NC+ radiotherapy group ( t=2.98, P=0.014). The SUV max of the NC+ radiotherapy group and shBRCA1+ radiotherapy group were reduced compared with those before radiotherapy ( t values: 5.82, 5.44, P values: 0.002, 0.003), while SUV max of the NC group and shBRCA1 group increased compared with those before radiotherapy ( t values: -4.47, -3.98, P values: 0.007, 0.011). TPV was smaller in the shBRCA1+ radiotherapy group compared with that in the NC+ radiotherapy group (0.48±0.03 vs 0.61±0.07; F=25.36, t=3.82, P=0.003). Immunohistochemical assays showed that Ki-67 was less expressed in the shBRCA1+ radiotherapy group than that in the NC+ radiotherapy group (0.286±0.072 vs 0.476±0.093; F=15.73, t=3.61, P=0.007). Correlation analysis showed a positive correlation between Ki-67 expression and SUV max ( r=0.83, P<0.001). Conclusion:18F-FLT microPET/CT imaging can evaluate the radiosensitizing effect of shBRCA1 expression on MDA-MB-231 breast cancer bearing nude mice.