The Role of Estrogen Receptor–Targeted PET with 16α-(18)F-Fluoro-17β-Estradiol in Predicting Response to Endocrine Therapies in Metastatic Breast Cancer - A Metaanalysis

Sep 29, 2026

Estrogen receptor–targeted PET/CT using 16α-[18F]fluoro-17β-estradiol (FES) supports whole-body assessment of functional ER expression in metastatic breast cancer. Identifying imaging biomarkers to forecast endocrine therapy response remains critical. A systematic review and metaanalysis through April 2024 included 10 quantitative SUV-based studies correlating FES PET/CT with outcomes in ER-positive metastatic patients receiving endocrine therapy. Baseline SUVmean/SUVmax and interlesional FES heterogeneity were evaluated versus progression-free survival and response.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Background and Objective

Imaging biomarker need in metastatic breast cancer

Study objective and endpoints

Methods

Systematic review and metaanalysis design

Inclusion criteria and patient characteristics

Imaging stratification (SUV thresholds and heterogeneity)

Results

Predictive value of baseline SUVmean and SUVmax

Impact of interlesional and lesion-level heterogeneity on PFS

Prognostic threshold analysis

Conclusion

Clinical implications for personalized endocrine therapy

The Role of Estrogen Receptor–Targeted PET with 16a-18F-Fluoro-17b-Estradiol in Predicting Response to Endocrine Therapies in Metastatic Breast Cancer: A Metaanalysis Jennifer M. Specht1, Jasper J.L. van Geel2, Shaoli Song3, Cheng Liu3, Daniel S. Hippe4, Nicholas A. DiGregorio5, Christine J. Brand5, and Hannah M. Linden1 1Division of Medical Oncology, Fred Hutchinson Cancer Center Clinical Research Division, Department of Medicine, University of Washington, Seattle, Washington; 2Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; 3Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; 4Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington; and 5Medical Affairs, GE HealthCare, Chicago, Illinois [18F]16a-ﬂuoro-17b-ﬂuoroestradiol ([18F]FES) PET/CT imaging enables whole-body assessment of functional estrogen receptor (ER) expression in metastatic breast cancer (mBC) . Identifying imaging biomarkers that predict endocrine therapy (ET) response remains a critical need in optimizing treatment selection. Our objective was to assess the predictive utility of [18F]FES PET/CT imaging in determining response to ET, with a focus on interlesional heterogeneity and individual patient outcomes. Methods: A systematic literature review and metaanalysis were conducted using 6 major databases through April 2024 . Ten studies met inclusion criteria based on quantitative SUV reporting, use of FES PET/CT in mBC, and correlation with clinical outcomes. All patients had ER-positive mBC and received ET. Primary endpoints included progression-free survival (PFS) and response to ET. Patients were stratiﬁed by baseline [18F]FES PET/CT SUVmean or SUVmax thresholds (including 1 .8) and by interlesional [18F]FES heterogeneity (presence of both [18F]FES-positive and [18F]FES-negative lesions) . Results: Responders had a signiﬁcantly higher baseline SUVmean than nonresponders (standardized mean difference, 0.91; 95% CI, 0.49– 1.34; P , 0.001) . Patients with a baseline SUVmax below 1.5 were signiﬁcantly less likely to respond (odds ratio, 0.11; 95% CI, 0.02–0.72; P 5 0.02) . Across 5 studies, patients with heterogeneous [18F]FES uptake had a shorter median PFS (2.4–12.4 mo) than did those with all [18F]FES-positive lesions (14 .6–23.6 mo), a statistically signiﬁcant difference (ratio of median PFS, 0.25; 95% CI, 0.17–0.36; P , 0.001). In an individual-level analysis (n 5 101), lesion-level [18F]FES-heterogeneous uptake was associated with a PFS of 5.5 versus 21.6 mo and a hazard ratio of 5.4 (95% CI, 3.2–9.4; P , 0.001). An [18F]FES SUVmax threshold of at least 1.8 was more prognostic of PFS than were higher SUVmax thresholds. Conclusion: [18F]FES PET/CT imaging provides prognostic insight beyond static ER testing by identifying functional heterogeneity in mBC. Lesion-level FES heterogeneity based on an SUVmax threshold of 1.8 may help stratify patients unlikely to beneﬁt from ET, guiding more personalized treatment strategies. Received Jul. 7, 2025; revision accepted Oct. 15, 2025 . For correspondence, contact Hannah M Linden ([hmlinden@uw.edu](hmlinden@uw.edu)) . Published online Dec. 4, 2025 . Immediate Open Access: Creative Commons Attribution 4.0 International License (CC BY) allows users to share and adapt with attribution, excluding materials credited to previous publications. License: [https://creativecommons](https://creativecommons). org/licenses/by/4.0/. Details: [https://jnm.snmjournals.org/page/permissions](https://jnm.snmjournals.org/page/permissions). COPYRIGHT 􀀁 2026 by the Society of Nuclear Medicine and Molecular Imaging. Key Words: radiopharmaceuticals; 16a-18 F-ﬂuoro-17b-estradiol; estrogen receptor; ﬂuoroestradiol; metastatic breast cancer;PET imaging J Nucl Med 2026; 67:36–42 DOI: 10.2967/jnumed.125.270763 treasghoutt ca

FAQs

What is the study’s primary goal regarding FES PET/CT in metastatic breast cancer?

To evaluate whether FES PET/CT can predict response to endocrine therapies in ER-positive metastatic breast cancer, with emphasis on interlesional heterogeneity and individual patient outcomes.

How were patients stratified for FES PET/CT analysis?

By baseline FES PET/CT SUVmean or SUVmax thresholds, and by interlesional FES heterogeneity defined by the presence of both FES-positive and FES-negative lesions.

What imaging findings were associated with better progression-free survival?

Responders showed higher baseline SUVmean than nonresponders, patients with baseline SUVmax below 1.5 were less likely to respond, and heterogeneous FES uptake was associated with shorter median PFS. A lesion-level SUVmax threshold of at least 1.8 was more prognostic for PFS.

Sep 29, 2026

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