title: Assessment of estrogen receptor expression in epithelial ovarian cancer patients using 16α-18F-fluoro-17β-estradiol PET/CT.
abstract: The estrogen receptor α (ERα) is expressed in approximately 70% of ovarian cancer tumors. PET of tumor ERα expression with the tracer 16α-(18)F-fluoro-17β-estradiol ((18)F-FES) may be valuable to select ovarian cancer patients for endocrine therapy. The aim of this study was to evaluate the feasibility of (18)F-FES PET to determine tumor ERα expression noninvasively in epithelial ovarian cancer patients.
  
  
  METHODS
  (18)F-FES PET/CT was performed shortly before cytoreductive surgery. Tumor (18)F-FES uptake was quantified for all lesions 10 mm or greater on CT and expressed as maximum standardized uptake value. (18)F-FES PET/CT findings were compared with histology and immunohistochemistry for ERα, ERβ, and progesterone receptor. Receptor expression was scored semiquantitatively using H-scores (percentage of positive tumor cells × staining intensity). The optimum threshold to discriminate ER-positive and -negative lesions was determined by receiver-operating-characteristic analysis.
  
  
  RESULTS
  In the 15 included patients with suspected ovarian cancer, 32 measurable lesions greater than 10 mm were present on CT. Tumor (18)F-FES uptake could be quantified for 28 lesions (88%), and 4 lesions were visible but nonquantifiable because of high uptake in adjacent tissue. During surgery, histology was obtained of 23 of 28 quantified lesions (82%). Quantitative (18)F-FES uptake correlated with the semiquantitative immunoscore for ERα (ρ = 0.65, P < 0.01) and weakly with progesterone receptor expression (ρ = 0.46, P = 0.03) and was not associated with ERβ expression (ρ = 0.21, P = 0.33). The optimum threshold to discriminate ERα-positive and ERα-negative lesions was a maximum standardized uptake value greater than 1.8, which provided a 79% sensitivity, 100% specificity, and area under the curve of 0.86 (95% confidence interval, 0.70-1.00). In 2 of 7 patients with cytology/histology available at primary diagnosis and at debulking surgery, immunohistochemical ERα expression had changed over time. (18)F-FES PET was in accordance with histology at debulking surgery but not at primary diagnosis, indicating that (18)F-FES PET could provide reliable information about current tumor ERα status.
  
  
  CONCLUSIONS
  (18)F-FES PET/CT can reliably assess ERα status in epithelial ovarian cancer tumors and metastases noninvasively. Evaluation of the predictive value of (18)F-FES PET/CT for endocrine therapy in epithelial ovarian cancer patients is warranted.
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Michel
authors.initials: M
authors.lastname: van Kruchten
authors.affiliation: Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Erik F J
authors.initials: EF
authors.lastname: de Vries
authors.affiliation: Gynecology, Division of Gynecological Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Henriette J G
authors.initials: HJ
authors.lastname: Arts
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Neeltina M
authors.initials: NM
authors.lastname: Jager
authors.affiliation: Radiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; and.
authors.forename: Alphons H H
authors.initials: AH
authors.lastname: Bongaerts
authors.affiliation: Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Andor W J M
authors.initials: AW
authors.lastname: Glaudemans
authors.affiliation: Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Hollema
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Geke A P
authors.initials: GA
authors.lastname: Hospers
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands a.k.l.reyners@umcg.nl.
authors.forename: Anna K L
authors.initials: AK
authors.lastname: Reyners
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000077216:Carcinoma, Ovarian Epithelial; D004958:Estradiol / Q000031:analogs & derivatives*; D005240:Feasibility Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D064847:Multimodal Imaging; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D049268:Positron-Emission Tomography; D011960:Receptors, Estrogen / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D011960:Receptors, Estrogen; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol; C043436:16-fluoroestradiol
keywords: FES PET; estrogen receptor; imaging; ovarian cancer