¹⁸F-fluoroestradiol for Molecular Imaging of Estrogen Receptor-Positive Breast Cancer

[¹⁸F]FES is FDA-approved since 2020, and is now distributed in Israel by S.R.Y Medical Services.

[¹⁸F]FES is an analogue of estradiol that binds the estrogen receptor (ER) with high affinity and selectivity¹.

It is indicated for detecting ER-positive lesions, as an adjunct to biopsy, in patients with recurrent or metastatic breast cancer². 

Current SNMMI/ EANM Appropriate Use Criteria for ER-Imaging of Breast Cancer Patients using [¹⁸F]FES deem the following indications as appropriate^3,4:

1. Assess ER status in lesions that are difficult to biopsy or when biopsy is nondiagnostic.
2. Guide therapy at the initial presentation of metastatic disease or after progression of metastatic disease.
3. Detect ER-expressing breast cancer lesions when other imaging tests are equivocal or suggestive.

Emerging indications requiring more evidence^3,4:

• Detect ER-expressing lesions in patients with suspected/ known recurrent or metastatic breast cancer.
• Assess ER status, in lieu of biopsy, in lesions that are easily accessible for biopsy.
• Stage invasive lobular breast cancer (ILC) and low-grade ER-expressing invasive ductal cancer.
• Routinely stage ER-expressing extra-axillary nodes and distant metastases.

PET images of two patients with metastatic invasive lobular carcinoma responding (A-C) and not responding (D-F) to palbociclib + letrozole  

^{Adapted with permission from Boers, J., et al. European Journal of Cancer. 2020; 126: 11-20}

Upper row responder: (A) Baseline [¹⁸F]FDG-PET shows pathological uptake in axillary lymph nodes (right side) and in nearly all vertebrae and pelvic bones. (B) Baseline [¹⁸F]FES-PET with pathological ER expression in the axial skeleton (vertebrae, pelvic bones, proximal humeri and femora) and in axillar lymph nodes. (C) [¹⁸F]FDG-PET after 8 weeks shows almost complete metabolic response. The patient has been on treatment for more than 70 weeks.

Lower row non-responder: (D) Baseline [¹⁸F]FDG-PET shows pathological uptake in multiple skeletal lesions. (E) Baseline [¹⁸F]FES-PET with only some increased ER expression in thoracic vertebrae. (F) [¹⁸F]FDG-PET after 8 weeks shows no metabolic response, with some increase in the pathologic uptake in the multiple skeletal lesions.

1. Katzenellenbogen, J. A., et al. Nucl Med Biol. 2021; 92: 24
2. https://www.gehealthcare.com/-/jssmedia/GEHC/US/Files/Products/Nuclear-Imaging-Agents/Cerianna/cerianna-pi
3. Ulaner, G. A., et al. J Nucl Med. 2023; 64: 351
4. Mankoff, D., Balogová, S., et al. J Nucl Med. 2024; 65: 221