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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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.
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.
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.
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.
Keywords18F-FES 18F-FDG Estrogen receptor alpha Fulvestrant Docetaxel insensitivity
Estrogen reporter alpha
Estrogen reporter alpha positive
Docetaxel-insensitive ERα+ breast cancer cells
DIS-ZR751 with fulvestrant treatment
DIS-ZR751 with docetaxel treatment
DIS-ZR751 with docetaxel and fulvestrant combination treatment
Cell counting kit-8
Quantitative reverse transcription PCR
Positron emission tomography/computed tomography
Region of interest
The max of percentage injected dose per gram
Epidermal growth factor receptor
Transforming growth factor alpha
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 6.Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, et al. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003;21:976–83.CrossRefPubMedGoogle Scholar
- 9.Ikeda H, Taira N, Nogami T, Shien K, Okada M, Shien T, et al. Combination treatment with fulvestrant and various cytotoxic agents (doxorubicin, paclitaxel, docetaxel, vinorelbine, and 5-fluorouracil) has a synergistic effect in estrogen receptor-positive breast cancer. Cancer Sci. 2011;102:2038–42.CrossRefPubMedGoogle Scholar
- 12.Yang Z, Sun Y, Xue J, Yao Z, Xu J, Cheng J, et al. Can positron emission tomography/computed tomography with the dual tracers fluorine-18 fluoroestradiol and fluorodeoxyglucose predict neoadjuvant chemotherapy response of breast cancer?—a pilot study. PloS one. 2013;8:e78192.CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. (San Diego, Calif) 2001;25:402–8.Google Scholar
- 15.Zhang YPZY., Wang MW, et al. Fully automated synthesis of 16a [18F] fluoro-17b-estrogen using Explora GN/LC dual module (in chinese). Zhonghua He Yi Xue Za Zhi. 2011;31:196–200.Google Scholar
- 21.Martin LA, Pancholi S, Chan CM, Farmer I, Kimberley C, Dowsett M, et al. The anti-oestrogen ICI 182, 780, but not tamoxifen, inhibits the growth of MCF-7 breast cancer cells refractory to long-term oestrogen deprivation through down-regulation of oestrogen receptor and IGF signalling. Endocr Relat Cancer. 2005;12:1017–36.CrossRefPubMedGoogle Scholar
- 24.He S, Wang M, Yang Z, Zhang J, Zhang Y, Luo J, et al. Comparison of 18F-FES, 18F-FDG, and 18F-FMISO pet imaging probes for early prediction and monitoring of response to endocrine therapy in a mouse xenograft model of ER-positive breast cancer. PloS one. 2016;11:e0159916.CrossRefPubMedPubMedCentralGoogle Scholar