Early Efficacy Of Ursolic Acid On Radiotherapy Sensitization In MCF-7 Breast Cancer Bearing Nude Mice Evaluated By ¹⁸F-FMISO Total-body PET/CT Dynamic Parametric Imaging

Objective¹⁸F-FMISO total-body PET/CT dynamic parameter imaging was used to image the nude mice bearing human MCF-7 breast cancer before and after radiotherapy sensitization treatment.To explore the value of ¹⁸F-FMISO total-body PET/CT dynamic parameter imaging in evaluating the early effect of ursolic acid（UA）on radiotherapy sensitization of MCF-7 breast cancer nude mice.MethodsTwenty-four MCF-7 breast cancer nude mice models were established and divided into four groups according to the random number table method（n=6 for each group）:control group,UA group,radiotherapy group,and UA+radiotherapy group.¹⁸F-FMISO total-body PET/CT dynamic parameter imaging was carried before and 24 h after radiotherapy,the tumor with the most intensive radioactive uptake was selected and the region of interest was outlined to obtain SUV_max-T and SUV_max-M.The ratio of SUV_max of tumor to muscle（T/M）were calculated.And the quantitative parameter—the maximum tracer uptake net inflow constants(Ki_max),was extracted by kinetic modeling.Observation and recording of tumor volume before and after treatment.After imaging,the expression of HIF-1α,GLUT-1,Ki-67 and VEGF were detected by immunohistochemistry.Data were analyzed by paired t-test,one-way ANOVA and Pearson correlation analysis.ResultsBefore radiotherapy,the differences in T/M（1.907±0.239、1.937±0.266、1.988±0.138 and 1.928±0.260;F=0.134）and Ki_max（0.052±0.012、0.053±0.010、0.058±0.015 and 0.058±0.012;F=0.475）between the control group,UA group,radiotherapy group and UA+radiotherapy group were not statistically significant（P=0.938、0.703）.After radiotherapy,T/M（2.823±0.354、2.780±0.367、1.575±0.280and 1.278±0.210;F=40.460）and Ki_max value（0.098±0.019、0.098±0.015、0.033±0.008 and 0.017±0.008;F=60.734）were statistically different（both P<0.001）between the above four groups.After radiotherapy,T/M and Ki_max values in the radiotherapy group and UA+radiotherapy group decreased compared with those before radiotherapy（t=6.499、5.839,P=0.001、0.002;t=10.997、13.558,both P<0.001）.And the difference in T/M between the radiotherapy and UA+radiotherapy groups was not statistically significant（t=1.661,P=0.112）,while the Ki_max was reduced in UA+radiotherapy group compared with radiotherapy group,and the difference was statistically significant（t=2.143,P=0.045）.Through the immunohistochemical results:the expression of HIF-1α,Glut-1,Ki-67,and VEGF were lower in UA+radiotherapy group than the other three groups（F=39.057,28.590、31.902、49.740,both P<0.001）.In addition,T/M values and Ki_max values were positively correlated with HIF-1αexpression（r=0.88,0.94,both P<0.01）.ConclusionUA has a radiosensitizing effect on MCF-7 breast cancer in nude mice,and ¹⁸F-FMISO total-body PET/CT dynamic parameter imaging can make early assessment of tumor hypoxia changes and evaluate the early efficacy of radiotherapy sensitization of breast cancer in nude mice more sensitively than conventional PET/CT static imaging.