A Phase 2 Study of 16α-[18F]-fluoro-17β-estradiol Positron Emission Tomography (FES-PET) as a Marker of Hormone Sensitivity in Metastatic Breast Cancer (MBC)

Abstract

Purpose 16α-[18F]-fluoro-17β-estradiol positron emission tomography (FES-PET) quantifies estrogen receptor (ER) expression in tumors and may provide diagnostic benefit. Procedures Women with newly diagnosed metastatic breast cancer (MBC) from an ER-positive primary tumor were imaged before starting endocrine therapy. FES uptake was evaluated qualitatively and quantitatively, and associated with response and with ER expression. Results Nineteen patients underwent FES imaging. Fifteen had a biopsy of a metastasis and 15 were evaluable for response. Five patients had quantitatively low FES uptake, six had at least one site of qualitatively FES-negative disease. All patients with an ER-negative biopsy had both low uptake and at least one site of FES-negative disease. Of response-evaluable patients, 2/2 with low FES standard uptake value tumors had progressive disease within 6 months, as did 2/3 with qualitatively FES-negative tumors. Conclusions Low/absent FES uptake correlates with lack of ER expression. FES-positron emission tomography can help identify patients with endocrine resistant disease and safely measures ER in MBC.

18F-Fluoroestradiol PET: Current Status and Potential Future Clinical Applications

“…Although it is currently considered an investigational drug in the United States, several American academic centers hold Investigational New Drug approvals that support studies involving 18 F-FES PET and 18 F-FES PET/CT. The National Cancer Institute also holds an Investigational New Drug approval (79,005)-enabled by a University of Washington study (16)-that can support multicenter trials in National Cancer Institute-supported clinical trial networks. There has been discussion in Europe and the United States of seeking regulatory approval for 18 F-FES on the basis of published studies and accruing data from prospective multicenter trials.…”

“…Among multiple metastatic sites in individual patients, 18 F-FES uptake was concordant with in vitro ER expression (33). Patients with discordant in vitro ER expression and 18 F-FES uptake (i.e., ER-positive but 18 F-FES-negative) tended to have a decreased response to hormone therapy, suggesting that 18 F-FES PET may identify tumor sites that are ER-positive by in vitro assay but functionally hormone therapy-resistant (16,33,34).…”

“…Several studies have demonstrated that although a primary tumor may have been ER-positive, its metastatic lesions may no longer express ER or may express only nonfunctional ERs (16,33,34). Because it is clinically infeasible to biopsy all sites of disease to determine overall ER expression, or to make a patient undergo repeated biopsies to evaluate tumor phenotype evolution, 18 F-FES PET imaging could represent an important adjunct for monitoring ER expression at the time of disease progression or throughout a treatment course.…”

Translation of New Molecular Imaging Approaches to the Clinical Setting: Bridging the Gap to Implementation

“…Predicting the response to endocrine therapy was examined in 8 trials comprising 240 patients. Absence of 18 F-FES uptake predicted the failure of endocrine therapy (38,39), and a decrease in uptake during therapy indicated a response to the antihormonal drugs tamoxifen and fulvestrant (40)(41)(42)(43).…”

Synthesis and pre-clinical evaluation of a [18F]fluoromethyl-tanaproget derivative for imaging of progesterone receptor expression

“…The use of the ER-targeted radioligand, 16α- involving primary and metastatic breast cancer. [8][9][10][11][12][13][14][15][16][17][18] Further integration of […”