Guang Ma1,2,3,4,5, Cheng Liu1,2,3,4,5, Weiling Lian1,2,3,4,5, Yongping Zhang1,2,3,4,5, Huiyu Yuan1,2,3,4,5, Yingjian Zhang1,2,3,4,5, Shaoli Song6,7,8,9,10, Zhongyi Yang11,12,13,14,15. 1. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No.270, Dong'an Road, Xuhui District, Shanghai, 200032, China. 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. 3. Center for Biomedical Imaging, Fudan University, Shanghai, 200032, China. 4. Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, 200032, China. 5. Department of Nuclear Medicine, Shanghai Proton and Heavy Ion Center, Shanghai, 201321, China. 6. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No.270, Dong'an Road, Xuhui District, Shanghai, 200032, China. shaoli-song@163.com. 7. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. shaoli-song@163.com. 8. Center for Biomedical Imaging, Fudan University, Shanghai, 200032, China. shaoli-song@163.com. 9. Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, 200032, China. shaoli-song@163.com. 10. Department of Nuclear Medicine, Shanghai Proton and Heavy Ion Center, Shanghai, 201321, China. shaoli-song@163.com. 11. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No.270, Dong'an Road, Xuhui District, Shanghai, 200032, China. yangzhongyi21@163.com. 12. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. yangzhongyi21@163.com. 13. Center for Biomedical Imaging, Fudan University, Shanghai, 200032, China. yangzhongyi21@163.com. 14. Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, 200032, China. yangzhongyi21@163.com. 15. Department of Nuclear Medicine, Shanghai Proton and Heavy Ion Center, Shanghai, 201321, China. yangzhongyi21@163.com.
Abstract
PURPOSE: Our study was to investigate 18F-FLT PET/CT imaging monitor the early response of CDK4/6 inhibitor therapy in triple negative breast cancer (TNBC). METHODS: MDA-MB-231 and MDA-MB-468 cell lines and corresponding subcutaneous tumor models in CB17-SCID mice were used. Cell viability assay, cell-cycle analysis, and western blotting were performed in vitro experiments. 18F-FLT PET/CT imaging was performed and the value of tumor/muscle (T/M) of mice was measured before and 1-3 days after treatment in vivo experiments. Then, the tumor volume was recorded every day for 15 days. RESULTS: In the presence of Palbociclib (CDK4/6 inhibitor), the results of in vitro experiments showed that protein pRB and E2F levels were significantly down-regulated in MDA-MB-231 cells leading to G0/G1 arrest with consumption in S phase compared with MDA-MB-468 cells. In PET/CT imaging, the 18F-FLT T/M ratio of treatment group was a significant and sustained reduction from 1 to 3 days (all p < 0.05) compared with control group in MDA-MB-231 section. However, there was no significant difference between treatment and control groups in MDA-MB-468 section. Compared with the control group, the tumor volume of the treatment group was significantly reduced from the 11th day in MDA-MB-231 section, but not in MDA-MB-468 section until 15 days. CONCLUSION: 18F-FLT PET/CT imaging can immediately and effectively monitor the early treatment response of CDK4/6 inhibitors in TNBC.
PURPOSE: Our study was to investigate 18F-FLT PET/CT imaging monitor the early response of CDK4/6 inhibitor therapy in triple negative breast cancer (TNBC). METHODS:MDA-MB-231 and MDA-MB-468 cell lines and corresponding subcutaneous tumor models in CB17-SCID mice were used. Cell viability assay, cell-cycle analysis, and western blotting were performed in vitro experiments. 18F-FLT PET/CT imaging was performed and the value of tumor/muscle (T/M) of mice was measured before and 1-3 days after treatment in vivo experiments. Then, the tumor volume was recorded every day for 15 days. RESULTS: In the presence of Palbociclib (CDK4/6 inhibitor), the results of in vitro experiments showed that protein pRB and E2F levels were significantly down-regulated in MDA-MB-231 cells leading to G0/G1 arrest with consumption in S phase compared with MDA-MB-468 cells. In PET/CT imaging, the 18F-FLT T/M ratio of treatment group was a significant and sustained reduction from 1 to 3 days (all p < 0.05) compared with control group in MDA-MB-231 section. However, there was no significant difference between treatment and control groups in MDA-MB-468 section. Compared with the control group, the tumor volume of the treatment group was significantly reduced from the 11th day in MDA-MB-231 section, but not in MDA-MB-468 section until 15 days. CONCLUSION: 18F-FLT PET/CT imaging can immediately and effectively monitor the early treatment response of CDK4/6 inhibitors in TNBC.
Entities:
Keywords:
18F-FLT; CDK4/6 inhibitor; Early treatment response; Monitor; Triple negative breast cancer
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