1.Radiosensitizing effect of silencing BRCA1 expression on MDA-MB-231 breast cancer bearing nude mice evaluating by 18F-FLT microPET/CT imaging
Weitao TAO ; Siqi WANG ; Yangyang XUE ; Alei XU ; Huiqin XU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(10):609-614
Objective: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.
2.Evaluation of Olaparib radiosensitization for breast cancer in nude mice by 18 F-FLT Micro PET / CT imaging
Siqi Wang ; Weitao Tao ; Alei Xu ; Yangyang Xue ; Hui Wang
Acta Universitatis Medicinalis Anhui 2023;58(6):930-934
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 ( SUVmax ) ,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 SUVmax with Ki-67 and PCNA was analyzed.
Results :
Before treatment,there were no significant differences in SUVmax , TPV and tumor volume among the 4 groups (F = 0. 041,0. 061,0. 045,P>0. 05) .48 h after treatment,SUVmax in the control and Olaparib groups increased significantly ( t = -12. 111,P <0. 001 ; t = -3. 001,P = 0. 03 ) , SUVmax was reduced in the radiotherapy and Olaparib + radiotherapy groups (t = 5. 829,P<0. 01 ; t = 4. 448,P < 0. 01) ,while SUVmax ,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) .SUVmax 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.