Early Evaluation On The Treatment Efficacy Of Tamoxifen On Breast Cancer By PET Imaging

PART ONE:Early Evaluation on the Treatment Efficacy of Tamoxifen on Breast Cancer Cells by 18F-FDG Objective To observe change of 18F-FDG uptake rate, early apoptosis and cell proliferation of MCF-7 cell with Tamoxifen, to analyse the relation between uptake rate of 18F-FDG and cell proliferation, and to assess the feasibility of 18F-FDG in early evaluation of the treatment effect on breast cancer with Tamoxifen. Methods To detect the uptake rate of 18F-FDG and cell proliferation on MCF-7 cell with different doses of TAM(5×10-6, 1×10-5, 1.5×10-5, 2×10-5 and 2.5×10-5mol/L). To assay the early apoptosis and cell cycle in MCF-7 cell by flow cytometry with half maximal inhibitory concentration(IC50) of TAM, and then to detect the expression change of ERα and ERβ. Results(1) The proliferation of MCF-7 cells was inhibited with different TAM doses. The growth inhibition of MCF-7 cell was(7.27±6.35)%,(21.12±7.91)%,(37.60±4.78)%,(42.52±6.20)% and(98.08±0.54)% at 24 h, and was(20.90±8.96)%,(33.01±13.85)%,(69.38±8.44)%,(95.62±1.12)% and(96.52±1.03)% at 48 h, respectively. When the doses of TAM were 5×10-6, 1×10-5, 1.5×10-5, 2×10-5 and 2.5×10-5mol/L, the individually proliferation of MCF-7 cells was negatively correlated with the doses of TAM(24h: P<0.05, r=0.93; 48h: P<0.01, r=0.97). The IC50 of TAM of MCF-7 cells was 1.95×10-5 mol/L at 24 h, and was 1.24×10-5 mol/L at 48 h.(2) The early apoptosis rate of MCF-7 cells with IC50 of TAM was(14.81±1.44)% at 24 h and(20.60±2.38)% at 48 h, higher than those in control group, which was(5.75±1.78)% at 24 h and(8.13±1.95) % at 48h(P<0.05). The percentage of cells in G0/G1 with IC50 of TAM was(57.24±6.90)% at 24 h and(79.36±9.72)% at 48 h, higher than those in control group, which was(29.08±3.09)% at 24 h and(32.64±5.87)% at 48h(P<0.05).(3) The expression of ERα in MCF-7 cells was decreased after they were treated with IC50 of TAM for 24 and 48 h.(4) The uptake rate of 18F-FDG in MCF-7 cells was decreased with different doses of TAM(5×10-6, 1×10-5, 1.5×10-5, 2×10-5, 2.5×10-5mol/L). The uptakes of 18F-FDG was(5.13±0.80)%,(19.73±7.16)%,(53.51±3.21)%,(66.30±8.92)% and(84.93±6.04)% at 24 h, and(9.07±0.63)%,(43.25±7.05)%,(62.53±1.56)%,(77.79±3.68)% and(87.57±4.75)% at 48 h. The uptakes of 18F-FDG in MCF-7 cells was negatively correlated with different doses of TAM(24h: P<0.01, r=0.99; 48h: P<0.01, r=0.97).(5) The proliferate inhibition rate in MCF-7 cells was positively correlated with the uptake inhibition rate of 18F-FDG with different doses of TAM at 24 and 48h(24h: P<0.05, r=0.91; 48h: P<0.05, r=0.96). Conclusions The proliferate inhibition rate of MCF-7 cells was positively correlated with the uptake inhibition rate of 18F-FDG after they were treated with TAM. 18F-FDG could be used to predict the response of TAM in MCF-7 cells. TAM could induce early apoptosis in MCF-7 cells. PART TWO:Early Evaluation on the Treatment Efficacy of Tamoxifen on Breast Cancer by 18F-FDG, 18F-FLT and 18F-FES micro PET Imaging Objective To examine the feasibility of 18F-FDG,18F-FLT and 18F-FES micro PET imaging on evaluation the effect of Tamoxifen on breast cancer, and to explore the imaging mechanism. Methods To establish the model of human breast cancer cell MCF-7 bearing nude mice. 10 tumor-bearing mouse were divided into control group and TAM-treatment group by random. To observe the change of tumor growth after they were treated with TAM. 20 tumor-bearing mouse were randomly divided into Control group, 18F-FDG PET imaging group, 18F-FLT PET imaging group and 18F-FES PET imaging group. 18F-FDG, 18F-FLT and 18F-FES PET Imaging were performed on tumor-bearing mouse after they were treated by TAM. Software was used to analysis the images and to compare the SUV changes oftumor. To analysis the expression changes of ERα, ERβ, GLUT-1, Ki-67 and PCNA of tumor specimen after they were treated by TAM. Results(1) 91% of tumor-bearing mouse were established. The tumor growth speed of mouse in treated group was lower than those in control group.(2) High uptake were shown in tumor sites of tumor-bearing on 18F-FDG, 18F-FLT and 18F-FES micro PET imaging After treatment of TAM, SUV of tumor sites on 18F-FLT and 18F-FES micro PET imaging were decreased. In 18F-FLT imaging: the pre-treatment SUVmax was 0.85±0.09, the post-treatment SUVmax was 0.72±0.08, △SUVmax was 0.13±0.11(t=3.012,P=0.039). In 18F-FES imaging: the pre-treatment SUVmax was 0.64±0.12, the post-treatment SUVmax was 0.64±0.12, △SUVmax was 0.32±0.03(t=12.930, P=0.006). While in 18F-FES imaging: the pre-treatment SUVmax was 1.12±0.16, the post-treatment SUVmax was 1.05±0.11(t=1.033, P=0.378).(3) After treatment, the expression of ERα, GLUT-1, Ki-67 and PCNA was decreased. However, no changes was found of ERβ expression. Conclusions The inhibition effect of TAM was observed on breast cancer tumor. The uptake rates of 18F-FLT and 18F-FES were decreased after treatment. 18F-FLT and 18F-FES micro PET imaging could be used to early predict the response of endocrine therapy on breast cancer.