title: Can fluorine-18 fluoroestradiol positron emission tomography-computed tomography demonstrate the heterogeneity of breast cancer in vivo?
abstract: OBJECTIVE
  Our study was to investigate the heterogeneity of estrogen receptor (ER) expression among tumor sites by using fluorine-18 ((18)F) fluoroestradiol (FES) positron-emission tomography-computed tomography (PET-CT) imaging.
  
  
  METHODS
  Thirty-two breast cancer patients underwent both (18)F-FES and (18)F fluorodeoxyglucose (FDG) PET-CTs from June 2010 to December 2011 in our center (mean age, 53 years; range, 27-77 years). We used the maximum standardized uptake value to quantify ER expression and a cutoff value of 1.5 to dichotomize results into ER(+) and ER(-). The difference of heterogeneity between the initial patients and patients with recurrent or metastatic disease after treatments was assessed by using the χ(2) test. Also, the (18)F-FES uptake was compared with the (18)F-FDG uptake by use of Spearman correlation coefficients.
  
  
  RESULTS
  A total number of 237 lesions in 32 patients were detected. Among them, most lesions (64.1% [152/237]) were bone metastasis. A striking 33.4-fold difference in (18)F-FES uptake was observed among different patients (maximum standardized uptake value range, 0.5 to approximately 16.7), and a 8.2-fold difference was observed among lesions within the same individual (1.0 to approximately 8.2). As for (18)F-FDG uptake, the difference was 11.6-fold (1.3 to approximately 15.1) and 9.9-fold (1.4 to approximately 13.8), respectively. In 28.1% (9/32) of the patients, both (18)F-FES(+) and (18)F-FES(-) metastases were present, which suggests partial discordant ER expression. After treatments, 37.5% (9/24) patients with recurrent or metastatic breast cancer showed heterogeneity, whereas no untreated patient was detected to exist discordant ER expression (χ(2), 4.174; P < .05). In addition, the (18)F-FES uptake showed a weak correlation with the (18)F-FDG uptake (ρ = 0.248; P < .05).
  
  
  CONCLUSIONS
  (18)F-FES and (18)F-FDG uptake varied greatly both within and among patients. (18)F-FES PET-CT demonstrated a conspicuous number of patients with the heterogeneity of ER expression.
authors.affiliation: Department of Nuclear Medicine, Shanghai Cancer Center, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Yang
authors.forename: Yifei
authors.initials: Y
authors.lastname: Sun
authors.forename: Yongping
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.forename: Mingwei
authors.initials: M
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Beiling
authors.initials: B
authors.lastname: Zhu
authors.forename: Silong
authors.initials: S
authors.lastname: Hu
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Yao
authors.forename: Herong
authors.initials: H
authors.lastname: Pan
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology; D004958:Estradiol / Q000031:analogs & derivatives*; D005260:Female; D005462:Fluorine Radioisotopes; D018740:Genetic Heterogeneity; D006801:Humans; D008875:Middle Aged; D064847:Multimodal Imaging; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography / Q000379:methods*; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D005462:Fluorine Radioisotopes; D011960:Receptors, Estrogen; D004958:Estradiol
keywords: Breast cancer; Estrogen receptor; Fluorine-18 fluorodeoxyglucose positron emission tomography; Heterogeneity; fluorine-18 fluoroestradiol positron emission tomography