^(18)F-FLT Micro PET/CT显像评价奥拉帕尼对裸鼠乳腺癌模型的放疗增敏作用

Evaluation of Olaparib radiosensitization for breast cancer in nude mice by^(18)F-FLT Micro PET/CT imaging

目的探讨^(18)F-脱氧胸腺嘧啶核苷(^(18)F-FLT)正电子发射计算机断层显像(PET/CT)评价奥拉帕尼(Olaparib)对裸鼠乳腺癌模型的放疗增敏作用。方法建立24只BALB/C裸鼠MCF-7乳腺癌模型,按随机数字表法分为4组,每组6只,分别为对照组、单纯放疗组、Olaparib组、Olaparib+放疗组,分别于治疗前和治疗后48 h对裸鼠行^(18)F-FLT Micro PET/CT显像。比较4组治疗前后肿瘤最大标准化摄取值(SUV max)、总增殖体积(TPV)及肿瘤体积的变化。显像完成后,取出肿瘤进行称重观察肿瘤质量变化。通过免疫组化法分析肿瘤增殖指数Ki-67及增殖细胞核抗原PCNA的表达情况,并分析肿瘤的SUV max与免疫组化指标Ki-67及PCNA的相关性。结果治疗前,4组肿瘤的SUV max、TPV及肿瘤体积差异无统计学意义(F=0.041、0.061、0.045,P>0.05);治疗结束后48 h,对照组和Olaparib组的肿瘤SUV max较治疗前升高(t=-12.111,P<0.001;t=-3.001,P=0.03);单纯放疗组和Olaparib+放疗组肿瘤的SUV max较治疗前减低(t=5.829,P<0.01;t=4.448,P<0.01),Olaparib+放疗组肿瘤的SUV max、TPV和肿瘤体积均低于单纯放疗组(t=3.388、5.884、5.990,P<0.01)。Olaparib+放疗组瘤体质量明显低于其他3组(F=44.405,P<0.001)。免疫组化检测显示Ki-67及PCNA在Olaparib+放疗组中表达均少于其他3组(F=16.289、39.645,P<0.001)。相关性分析显示SUV max与Ki-67及PCNA表达均呈正相关(r=0.920、0.918,P<0.01)。结论^(18)F-FLT Micro PET/CT显像可以评价Olaparib对裸鼠乳腺癌模型的放疗增敏作用。

Objective To investigate the effect of^(18)F-deoxythymidine nucleoside(^(18)F-FLT)positron emission computed tomography(PET/CT)imaging to evaluate the radiosensitization effect of Olaparib on breast cancer model in nude mice.Methods According to the random number table method,twenty-four BALB/C nude mice MCF-7 breast cancer models were established and divided into four groups with 6 mice in each group,namely the control group,radiotherapy group,Olaparib group and Olaparib+radiotherapy group.^(18)F-FLT micro PET/CT imaging was performed on nude mice before and 48 h after treatment,respectively.The changes of maximum standardized uptake value(SUV max),total proliferation volume(TPV)and tumor volume before and after tumor treatment in four groups were compared.The tumors were extracted and weighed to observe the changes of tumor weight,and the expression of Ki-67 and PCNA was analyzed by immunohistochemistry staining.The correlation of tumor SUV max with Ki-67 and PCNA was analyzed.Results Before treatment,there were no significant differences in SUV max,TPV and tumor volume among the 4 groups(F=0.041,0.061,0.045,P>0.05).48 h after treatment,SUV max in the control and Olaparib groups increased significantly(t=-12.111,P<0.001;t=-3.001,P=0.03),SUV max was reduced in the radiotherapy and Olaparib+radiotherapy groups(t=5.829,P<0.01;t=4.448,P<0.01),while SUV max,TPV and tumor volume of tumors in the Olaparib+radiotherapy group were lower than those in the radiotherapy group(t=3.388,5.884,5.990,P<0.01).Tumor weight was significantly lower in the Olaparib+radiotherapy group than in the other three groups(F=44.405,P<0.001).Immunohistochemical staining showed that Ki-67 and PCNA were the least expressed in the Olaparib+radiotherapy group than in the other three groups(F=16.289,39.645,P<0.001).SUV max was positively correlated with Ki-67 and PCNA expression(r=0.920,0.918,P<0.01).Conclusion^(18)F-FLT Micro PET/CT imaging can evaluate the radiosensitizing effect of Olaparib on nude mouse breast cancer model.