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Background
18F-Fluoroestradiol (FES) is a newly U.S. Food and Drug Administration (FDA)-approved PET imaging agent. The clinical use of FES-PET imaging for breast cancer evaluation is not yet widespread. To aid adoption and awareness, this presentation educates radiologists and nuclear medicine physicians on the performance and interpretation of FES-PET imaging.

Educational Goals / Teaching Points
After reviewing this presentation, the learner will identify current FDA-approved indications for 18F-Fluoroestradiol (FES) PET imaging, understand the normal biodistribution of FES on PET images, delineate how abnormal FES-PET uptake is determined, and master common pearls and pitfalls for FES-PET/CT imaging interpretation.

Key Anatomic/Physiologic Issues and Imaging Findings/Techniques
Current FDA-approved uses of FES-PET imaging include use as an adjunct to biopsy for identification of estrogen receptor (ER)-positive lesions, identification of biopsy target(s), assessment of ER heterogeneity among sites of malignancy, and to clarify equivocal findings on FDG-PET or other imaging modalities. Important precautions for FES-PET imaging include understanding that FES uptake is reduced when patients are taking drugs that block ERs. FES-PET imaging should not be performed within 8 weeks of tamoxifen use and 28 weeks of fulvestrant use. Aromatase inhibitors do not block ERs, and imaging can be performed while on an aromatase inhibitor. FES does not replace biopsy when biopsy is indicated. Normal biodistribution includes intense physiologic hepatobiliary and urinary uptake, normal venous uptake in extremity on injection side, minimal brain and bone marrow uptake, low-level diffuse physiologic breast uptake, and variable endometrial uptake. Abnormal FES-PET uptake is defined as local uptake above local (organ-specific) background and above blood pool activity. Many clinical trials use a threshold SUVmax of = 1.5 for abnormal FES uptake. Abnormal FES uptake can be faint and often requires windowing to identify disease above normal background uptake levels, especially when evaluating tissues with high physiologic uptake such as the liver. Pearls and pitfalls for FES-PET/CT interpretation will be discussed. Appropriate windowing is required for interpretation (breast = narrow windowing (upper SUVmax ˜ 5 or less) and liver/bowel = wide windowing (upper SUVmax ˜ 20)). Findings of high suspicion for ER+ metastatic disease include focal uptake in axillary lymph nodes above background, focal brain uptake (exception is meningioma), and focal or diffuse bone uptake. Abnormal FES uptake is not expected with inflammation (e.g., post-biopsy change), trauma (e.g., rib fracture), reactive lymph nodes (e.g., following COVID vaccination) and ER-metastases.

Conclusion
FES-PET imaging is FDA approved for in vivo assessment of ERs at sites of breast cancer. This presentation provides an overview of key topics for the performance and interpretation of FES-PET imaging to improve understanding and facilitate use of this imaging agent.