18F-FLT microPET/CT显像评价沉默BRCA1表达对MDA-MB-231乳腺癌裸鼠模型的放疗增敏作用  

Radiosensitizing effect of silencing BRCA1 expression on MDA-MB-231 breast cancer bearing nude mice evaluating by 18F-FLT microPET/CT imaging

作　　者：陶伟涛 王思淇 薛杨央[1] 许阿磊 徐慧琴[1] Tao Weitao;Wang Siqi;Xue Yangyang;Xu Alei;Xu Huiqin(Department of Nuclear Medicine,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China)

机构地区：[1]安徽医科大学第一附属医院核医学科,合肥230022

出　　处：《中华核医学与分子影像杂志》2023年第10期609-614,共6页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家自然科学基金(81971643)。

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。ObjectiveTo 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.MethodsTwenty-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 SUVmax 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.ResultsBreast cancer cells targeting the BRCA1 were constructed.Before radiotherapy,the differences of SUVmax 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 SUVmax 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 SUVmax in the shBRCA1+radiotherapy group compared with the NC+radiotherapy group(t=2.98,P=0.014).The SUVmax 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 SUVmax 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

关 键 词：乳腺肿瘤 基因沉默 BRCA1蛋白质 辐射增敏药 双脱氧核苷类 正电子发射断层显像术 体层摄影术 X线计算机 小鼠 裸 

分 类 号：R737.9[医药卫生—肿瘤] R730.44[医药卫生—临床医学]