PET Imaging of Estrogen Receptors Using ¹⁸F-Based Radioligands

In vivo molecular imaging of estrogen receptor alpha (ER) can be performed via positron emission tomography (PET) using ER-specific radioligands, such as 16α-[¹⁸F]fluoro-17β-estradiol (¹⁸F-FES). ¹⁸F-FES is a radiopharmaceutical recently approved by the United States Food and Drug Administration for use with PET imaging to detect ER+ lesions in patients with recurrent or metastatic breast cancer as an adjunct to biopsy. ¹⁸F-FES PET imaging has been used in clinical studies and preclinical research to assess whole-body ER protein expression and ligand binding function across multiple metastatic sites, to demonstrate inter-tumoral and temporal heterogeneity of ER expression, to quantify the pharmacodynamic effects of ER antagonist treatment, and to predict endocrine therapy response. ¹⁸F-FES PET has also been studied for imaging ER in endometrial and ovarian cancer. This chapter details the experimental protocol for ¹⁸F-FES PET imaging of ER in preclinical tumor xenograft models. Consistent adherence to key methodologic details will facilitate obtaining meaningful and reproducible ¹⁸F-FES PET preclinical imaging results, which could yield additional insight for clinical trials regarding imaging biomarkers and oncologic therapy.