18F-Fluoroestradiol (FES) PET/CT: review of current practice and future directions

Purpose: This expert review describes the development and foundational studies of [¹⁸F]fluoroestradiol (¹⁸F-FES) in the setting of imaging estrogen receptor (ER)-positive breast cancer. We detail the current and emerging clinical applications of ¹⁸F-FES PET/CT, emphasizing the underlying biology of the radiotracer. We conclude with a discussion of future applications of ¹⁸F-FES PET/CT in breast cancer and other malignancies. Methods: This review is based on a selection of foundational and recent publications available on PubMed. Results: Developed in the 1980s, ¹⁸F-FES targets the ER, representing the first receptor-targeted PET radiotracer for oncologic imaging. Over the course of the next few decades, studies established the tracer as an in vivo measure of estrogen expression. In 2016, ¹⁸F-FES was approved for clinical use in France in patients with recurrent, initially ER-positive breast cancer in whom biopsy is deemed impossible. In 2020, ¹⁸F-FES was approved in the USA for the detection of ER-positive lesions as an adjunct to biopsy to help guide management in patients with recurrent or metastatic breast cancer. Numerous clinical trials are currently underway investigating expanded uses for ¹⁸F-FES in breast cancer patients as well as other patient populations. Discussion: Currently approved for clinical use in France and the USA in patients with recurrent or metastatic ER-positive breast cancer, ¹⁸F-FES PET/CT can inform treatment decisions in this patient population. Investigational uses of ¹⁸F-FES PET/CT include answering specific clinical questions in the setting of an equivocal conventional workup, serving as a biomarker to predict treatment response, staging newly diagnosed disease, and assessing ER blockade. Conclusion: As a non-invasive in vivo marker of a biologically relevant structure, and a drug target, ¹⁸F-FES has advanced precision medicine, with potential for an even greater impact in the coming years.