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18F-FLT PET/CT imaging for early monitoring response to CDK4/6 inhibitor therapy in triple negative breast cancer

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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.

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Acknowledgements

We are very grateful for all the authors. And the authors declare that they have no competing interests.

Funding

This study was supported by the Shanghai Committee of Science and Technology Fund (No.19ZR1411300), the Shanghai Engineering Research Center of Molecular Imaging Probes Program (No. 19DZ2282200), the Shanghai Sailing Program (20YF1408500), Shanghai Municipal Health Commission (No. 202040269) and the Science and Technology Development Fund of Shanghai Pudong New Area (PKJ2020-Y54).

Author information

Author notes

  1. Guang Ma, Cheng Liu and Weiling Lian have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, No.270, Dong’an Road, Xuhui District, Shanghai, 200032, China

    Guang Ma, Cheng Liu, Weiling Lian, Yongping Zhang, Huiyu Yuan, Yingjian Zhang, Shaoli Song & Zhongyi Yang

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Guang Ma, Cheng Liu, Weiling Lian, Yongping Zhang, Huiyu Yuan, Yingjian Zhang, Shaoli Song & Zhongyi Yang

  3. Center for Biomedical Imaging, Fudan University, Shanghai, 200032, China

    Guang Ma, Cheng Liu, Weiling Lian, Yongping Zhang, Huiyu Yuan, Yingjian Zhang, Shaoli Song & Zhongyi Yang

  4. Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, 200032, China

    Guang Ma, Cheng Liu, Weiling Lian, Yongping Zhang, Huiyu Yuan, Yingjian Zhang, Shaoli Song & Zhongyi Yang

  5. Department of Nuclear Medicine, Shanghai Proton and Heavy Ion Center, Shanghai, 201321, China

    Guang Ma, Cheng Liu, Weiling Lian, Yongping Zhang, Huiyu Yuan, Yingjian Zhang, Shaoli Song & Zhongyi Yang

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Correspondence to Shaoli Song or Zhongyi Yang.

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Ma, G., Liu, C., Lian, W. et al. 18F-FLT PET/CT imaging for early monitoring response to CDK4/6 inhibitor therapy in triple negative breast cancer. Ann Nucl Med 35, 600–607 (2021). https://doi.org/10.1007/s12149-021-01603-w

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  • DOI: https://doi.org/10.1007/s12149-021-01603-w

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