18 F-Fluoroestradiol: Current Applications and Future Directions

In the United States, breast cancer is the second leading cause of cancer death in all women and the leading cause of cancer death in Black women. The breast cancer receptor profile, assessed with immunohistochemical staining of tissue samples, allows prediction of outcomes and direction of patient treatment. Approximately 80% of newly diagnosed breast cancers are hormone receptor (HR) positive, which is defined as estrogen receptor (ER) and/or progesterone receptor (PR) positive. Patients with ER-positive disease can be treated with therapies targeting the ER; however, the assessment of ER expression with immunohistochemical staining of biopsy specimens has several limitations including sampling error, false-negative results, challenging or inaccessible biopsy sites, and the inability to synchronously and serially assess all metastatic sites to identify spatial and/or temporal ER heterogeneity. In May 2020, after decades of research, the U.S. Food and Drug Administration approved the PET radiotracer fluorine 18 ( F) fluoroestradiol (FES) for clinical use in patients with ER-positive recurrent or metastatic breast cancer as an adjunct to biopsy. FES binds to the ER in the nucleus of ER-expressing cells, enabling whole-body in vivo assessment of ER expression. This article is focused on the approved uses of FES in the United States, including identification of a target lesion for confirmatory biopsy, in vivo assessment of biopsy-proven ER-positive disease, and evaluation of spatial and temporal ER heterogeneity. FES is an example of precision medicine that has been leveraged to optimize the care of patients with breast cancer. RSNA, 2023 See the invited commentary by Fowler in this issue. Quiz questions for this article are available through the Online Learning Center.