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).
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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