Assessment of Estrogen Receptor Expression in Epithelial Ovarian Cancer Patients Using 16α-18F-Fluoro-17β-Estradiol PET/CT

The estrogen receptor a (ER alpha) is expressed in approximately 70% of ovarian cancer tumors. PET of tumor ER alpha expression with the tracer 16 alpha-F-18-fluoro-17 beta-estradiol (F-18-FES) may be valuable to select ovarian cancer patients for endocrine therapy. The aim of this study was to evaluate the feasibility of F-18-FES PET to determine tumor ERa expression noninvasively in epithelial ovarian cancer patients. Methods: F-18-FES PET/CT was performed shortly before cytoreductive surgery. Tumor F-18-FES uptake was quantified for all lesions 10 mm or greater on CT and expressed as maximum standardized uptake value. F-18-FES PET/CT findings were compared with histology and immunohistochemistry for ER alpha, ER beta, and progesterone receptor. Receptor expression was scored semiquantitatively using H-scores (percentage of positive tumor cells Chi 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 F-18-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 F-18-FES uptake correlated with the semiquantitative immunoscore for ER alpha (rho = 0.65, P < 0.01) and weakly with progesterone receptor expression (rho - 0.46, P - 0.03) and was not associated with ER beta expression (rho = 0.21, P = 0.33). The optimum threshold to discriminate ER alpha-positive and ER alpha-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 ERa expression had changed over time. F-18-FES PET was in accordance with histology at debulking surgery but not at primary diagnosis, indicating that F-18-FES PET could provide reliable information about current tumor ERa status. Conclusion: F-18-FES PET/CT can reliably assess ERa status in epithelial ovarian cancer tumors and metastases noninvasively. Evaluation of the predictive value of F-18-FES PET/CT for endocrine therapy in epithelial ovarian cancer patients is warranted.