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The feasibility of 18F-FES and 18F-FDG microPET/CT for early monitoring the effect of fulvestrant on sensitizing docetaxel by downregulating ERα in ERα+ breast cancer

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Abstract

Objective

Our study aimed to investigate the feasibility of PET/CT for monitoring the influence of fulvestrant on sensitizing docetaxel by downregulating ERα in ERα+ breast cancer.

Methods

Docetaxel-insensitive ERα+ breast cancer cells (DIS-ZR751) were established, identified and cultured. ERα expression, toxicity and viability of DIS-ZR751 were analyzed before and after treatment in vitro. DIS-ZR751-bearing nude mice were randomly divided into four groups according to different treatments: blank (DIS-ZR751), docetaxel (DIS-ZR751+DOC), fulvestrant (DIS-ZR751+FUL), and combination treatment (DIS-ZR751+DOC+FUL). 18F-FES and 18F-FDG microPECT/CT scans were performed before and 7, 14 days after treatment. Absolute %ID/gmax was calculated.

Results

ERα expression level and growth rate of DIS-ZR751 were higher than control group and decreased dramatically after docetaxel and fulvestrant combination treatment. 18F-FES and 18F-FDG PET/CT imaging in vivo revealed that ERα expression in DIS-ZR751 treated with fulvestrant, and tumor activity in DIS-ZR751 treated with combination drugs decreased as early as 7 days after treatment.

Conclusions

18F-FES and 18F-FDG PET/CT were feasible for early monitoring the effect of fulvestrant on sensitizing docetaxel by downregulation of ERα in ERα+ breast cancer noninvasively.

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Abbreviations

ER:

Estrogen reporter alpha

ERα+:

Estrogen reporter alpha positive

DIS-ZR751:

Docetaxel-insensitive ERα+ breast cancer cells

DIS-ZR751+FUL:

DIS-ZR751 with fulvestrant treatment

DIS-ZR751+DOC:

DIS-ZR751 with docetaxel treatment

DIS-ZR751+DOC+FUL:

DIS-ZR751 with docetaxel and fulvestrant combination treatment

FBS:

Fetalbovine serum

dNTP:

Deoxy-ribonucleoside triphosphate

RNasin:

RNase inhibitor

CCK8:

Cell counting kit-8

RT-qPCR:

Quantitative reverse transcription PCR

18F-FDG:

2-deoxy-2-[18F]fluoro-d-glucose

18F-FES:

16α-[18F]fluoro-17β-estrogen

PET/CT:

Positron emission tomography/computed tomography

ROC:

Region of interest

%ID/gmax :

The max of percentage injected dose per gram

EGFR:

Epidermal growth factor receptor

TGF-α:

Transforming growth factor alpha

IHC:

Immunohistochemical analysis

GLUT-1:

Glucose transporter-1

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Acknowledgements

We wish to thank Jianmin Luo for excellent technical assistances. This study was funded by the Shanghai Committee of Science and Technology Fund (15ZR1407600) for Zhongyi Yang.

Funding

This study was funded by the Shanghai Committee of Science and Technology Fund (15ZR1407600).

Author information

Author notes

  1. Shuai Liu and Bingxin Gu equally contributed.

Authors and Affiliations

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

    Shuai Liu, Bingxin Gu, Jianping Zhang, Yongping Zhang, Xiaoping Xu, Huiyu Yuan, Yingjian Zhang & Zhongyi Yang

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

    Shuai Liu, Bingxin Gu, Jianping Zhang, Yongping Zhang, Xiaoping Xu, Huiyu Yuan, Yingjian Zhang & Zhongyi Yang

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

    Shuai Liu, Bingxin Gu, Jianping Zhang, Yongping Zhang, Xiaoping Xu, Huiyu Yuan, Yingjian Zhang & Zhongyi Yang

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

    Shuai Liu, Bingxin Gu, Jianping Zhang, Yongping Zhang, Xiaoping Xu, Huiyu Yuan, Yingjian Zhang & Zhongyi Yang

  5. Key Laboratory of Nuclear Physics and Ion-beam Application(MOE), Fudan University, Shanghai, China

    Shuai Liu, Bingxin Gu, Jianping Zhang, Yongping Zhang, Xiaoping Xu, Huiyu Yuan, Yingjian Zhang & Zhongyi Yang

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  1. Shuai Liu
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Correspondence to Zhongyi Yang.

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Liu, S., Gu, B., Zhang, J. et al. The feasibility of 18F-FES and 18F-FDG microPET/CT for early monitoring the effect of fulvestrant on sensitizing docetaxel by downregulating ERα in ERα+ breast cancer. Ann Nucl Med 32, 272–280 (2018). https://doi.org/10.1007/s12149-018-1245-0

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  • DOI: https://doi.org/10.1007/s12149-018-1245-0

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