Dynamic and Test-retest Whole Body [18F]FES PET Imaging in Patients With Metastatic ER+ Breast Cancer (FEStastic)

16a-18F-fluoro-17b-estradiol ([18F]FES) is radioactive labeled estradiol, developed for in vivo visualization of the estrogen receptor (ER) using positron emission tomography (PET). To date, [18F]FES PET has been mainly explored as a diagnostic imaging tool to assess ER expression, thereby identifying locations of disease and their potential sensitivity to endocrine therapy, respectively. The primary aim of this project is to extend the application of [18F]FES PET as a baseline diagnostic imaging biomarker for ER expression to use it as an (early) treatment response marker. However, for such an application, visual assessment alone may not be sufficient and a more rigorous quantitative image analysis is needed. Therefore, in this project we shall first derive the optimal pharmacokinetic model for full quantitative analysis of [18F]FES uptake and, subsequently, we shall assess the validity of simplified, clinically feasible, quantitative parameters of [18F]FES uptake in 5 patients with metastatic estrogen receptor positive (ER+) breast cancer (part A). In addition, the repeatability of these simplified parameters will then be investigated in another 10 patients (part B).

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: FES

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1081 HV
      • Amsterdam UMC - location VUMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically proven metastatic ER+ (>10% positive stained cells using immunohistochemistry) breast cancer on the latest biopsy

• Postmenopausal females aged 18 years or older at screening. Postmenopausal status is defined as one of the following:

  1. age ≥60 years
  2. age <60 years and amenorrhea for >12 months in the absence of interfering hormonal therapies (such as LH-RH agonists and ER-antagonists)
  3. patient age <60 years using LH-RH agonists should continue LH- RH-agonists until after the PET procedures
  4. previous bilateral oophorectomy or medically confirmed ovarian failure
• [18F]FDG PET, CT and/or a bone scan should be performed as part of routine clinical staging (≤4 weeks prior to screening)
• Patients should have metastases in the scanning field of view, all located outside of the liver
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2
• Estimated glomerular filtration rate (eGFR) ≥30 ml/min
• Written and signed informed consent

Exclusion Criteria:

• History with another cancer within the last 5 years, except cancer treated with curative intent and no evidence of disease as judged by the treating physician
• Use of selective estrogen receptor modulators (SERMs) or downregulators (SERDs) for current breast cancer such as Tamoxifen/Fulvestrant (≤5 weeks prior to screening) or investigational drug therapy
• Pregnancy or lactating women
• Any medical, psychological or social condition that may interfere with the subject's safety and participation in the study, will lead to exclusion from this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: dynamic FES PET imaging; All patients included in part A will receive a dynamic FES PET/CT scan.	Drug: FES; [18F]FES PET imaging.
Experimental: Part B: whole body static FES PET imaging; All patients included in part B will receive a whole body static FES PET/CT scan twice within 1 week.	Drug: FES; [18F]FES PET imaging.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FES uptake in lesions: Ki (net influx rate) or VT (volume of distribution) values	FES uptake in lesions will be expressed as Ki or VT values	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SUV and TBR values	Quantification of FES uptake in lesions will be assessed by determining standardized uptake values and tumor-to-blood ratios.	1 year.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
SUV and TBR values	Repeatability of standardized uptake values and tumor-to-blood ratios will be assessed.	1 year.

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 7, 2021
• First Submitted That Met QC Criteria: October 8, 2021
• First Posted (Actual): October 22, 2021

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: NL76658.029.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No