The feasibility of 18 F-FES and 18 F-FDG microPET/CT for early monitoring the effect of fulvestrant on sensitizing docet

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ORIGINAL ARTICLE

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 Shuai Liu1,2,3,4,5 · Bingxin Gu1,2,3,4,5 · Jianping Zhang1,2,3,4,5 · Yongping Zhang1,2,3,4,5 · Xiaoping Xu1,2,3,4,5 · Huiyu Yuan1,2,3,4,5 · Yingjian Zhang1,2,3,4,5 · Zhongyi Yang1,2,3,4,5 Received: 15 December 2017 / Accepted: 20 February 2018 © The Japanese Society of Nuclear Medicine 2018

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. Keywords  18F-FES · 18F-FDG · Estrogen receptor alpha · Fulvestrant · Docetaxel insensitivity Abbreviations ER Estrogen reporter alpha ERα+ Estrogen reporter alpha positive Shuai Liu and Bingxin Gu equally contributed. * Zhongyi Yang [email protected] 1



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

2



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

3

Center for Biomedical Imaging, Fudan University, Shanghai, China

4

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

5

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



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 18 F-FDG 2-deoxy-2-[18F] fluoro-d-glucose 18 F-FES 16α-[18F]fluoro-17β-estrogen

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