European Nuclear Medicine Guide
16α-[18F]fluoro-17β-estradiol ([18F]FES) is an oestradiol analogue with high binding affinity for oestrogen receptors (ER) and the steroid transport protein, sex hormone-binding globulin (SHBG). It is currently the only ER-targeted PET tracer approved for clinical use.
[18F]FES is a close analogue of oestradiol and has high binding affinity for the ER and SHBG. After injection, [18F]FES promptly accumulates in ER-expressing tissue in the first 20–30 minutes, with uptake plateauing at approximately 60 minutes post-injection. Like other steroids, [18F]FES is rapidly metabolized by the liver into sulphate and glucuronide conjugates that are excreted in bile and enter enterohepatic circulation. Local saturation of SHBG at the injection site affects uptake along the injecting vein.
Primary indications for [18F]FES PET in breast cancer patients include:
Assessment of lesions that are difficult to biopsy or where biopsy is nondiagnostic
Guiding therapy after the progression of metastatic disease
Guiding therapy at the initial presentation of metastatic disease
Detection of ER-expressing breast cancer sites when other imaging tests are equivocal
Emerging indications include:
Detection of ER-expressing lesions in suspected/known recurrent or metastatic breast cancer
Assessment of ER status instead of biopsy for easily accessible lesions
Staging of invasive lobular breast cancer and low-grade ER-expressing invasive ductal cancer
Staging of ER-expressing extra-axillary nodes and distant metastases
Pregnancy; breastfeeding interruption for at least 4 hrs
Current use of ER-blocking medications (requires a washout period):
Tamoxifen: minimum 6-week withdrawal
Fulvestrant: 28-week withdrawal recommended
Novel oral SERDs:
Elacestrant: has a half-life of 27–47 hours, optimal withdrawal period to be determined
Rintodestrant: FES uptake is restored ≥ 5 days after treatment withdrawal
Diagnostic Accuracy:
High sensitivity (86%) and specificity (85%) for detecting ER-expressing lesions [414]
Better accuracy in bone metastases compared to lymph node metastases
Limited accuracy for liver metastases due to high physiological uptake
Primary Tumour Detection:
Role in primary tumour identification remains controversial
Limited specificity for distinguishing between neoplastic and benign pathological conditions
Not recommended for routine primary tumour staging
Lymph Node Staging:
Limited spatial resolution may result in false negatives for micrometastases
Lymph nodes with SUVmax 1.5–2.5 show relatively high false-positive rates
Value in detecting extra-axillary nodal involvement in selected cases
Metastatic Disease:
High clinical utility in the metastatic setting, particularly for bone metastases
Can detect ER-expressing brain metastases due to low background uptake
Valuable for characterizing equivocal findings on conventional imaging
Can demonstrate heterogeneity of ER expression across metastatic sites
Treatment Response Prediction:
High negative predictive value – lesions without FES uptake (SUVmax <1.5) typically lack response to hormone treatment [415]
Heterogeneous [18F]FES uptake is associated with poorer survival and shorter treatment response
Serial [18F]FES PET can assess the adequacy of ER blockade during treatment
Impact on Patient Management:
Valuable for guiding therapy decisions in the metastatic setting
Can help identify patients likely to benefit from endocrine therapy [397]
Valuable for selecting biopsy sites in cases of suspected disease progression
Comparison with Other Modalities [398]:
Complementary to [18F]FDG PET in characterizing disease phenotype
Can detect lesions missed by conventional imaging in some cases
Valuable for invasive lobular carcinoma and low-grade ER+ invasive ductal carcinoma [399]
Combined interpretation with [18F]FDG PET can help differentiate between indolent and aggressive disease
Recommended activity: 111–280 MBq (3–7.6 mCi)
Single IV injection of ≤10 mL
Slow administration over 1–2 minutes is recommended
Use of a larger gauge IV catheter (20G or larger) is recommended
The effective dose for [18F]FES is approximately 0.022-0.025 mSv/MBq. The organs receiving the highest doses are: [416]
Liver: 0.13 mGy/MBq
Gallbladder: 0.10 mGy/MBq
Urinary bladder: 0.05 mGy/MBq
Normal biodistribution includes:
High uptake in the liver
Biliary excretion with activity in the small bowel
Moderate renal/bladder activity
Physiological uptake in uterus, pituitary, ovaries
Potential retention in the injection site veins
Positive findings:
Extrahepatic lesions with uptake greater than local tissue/vascular background
SUVmax ≥ 1.5 suggests ER expression
Consider higher thresholds for certain regions (e.g., lumbar spine)
False positives can occur in:
Post-radiation changes (particularly in lung [400])
Bone conditions (e.g., fibrous dysplasia, insufficiency fractures)
Benign ER-expressing lesions (e.g., meningiomas, uterine leiomyomas)
Physiological uptake sites
Other ER-expressing malignancies (e.g., endometrial and ovarian cancer)
False negatives can occur due to:
Small lesion size (partial volume effects)
Proximity to high physiological uptake
Recent ER-blocking therapy
Liver metastases (masked by normal liver uptake)
No fasting required
Pregnancy test if indicated
Documentation of menopausal status
Review and documentation of current/prior ER-targeted therapies
Review of the most recent conventional imaging
Uptake time: 20–80 minutes post-injection (60 minutes recommended)
Imaging range: vertex to mid-thigh or toes
Patient position: supine, arms overhead
Total scan time: approximately 20–30 minutes
CT parameters as per institutional protocol for PET/CT imaging
The detailed recommendations are available in the SNMMI Procedure Standard/EANM Practice Guideline for Estrogen Receptor Imaging of Patients with Breast Cancer Using 16a-[18F]Fluoro-17b-Estradiol PET