[18F]FDG and [18F]FES PET/CT Imaging as a Biomarker for Therapy Effect in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant

Ramsha Iqbal*, Maqsood Yaqub, Husseyin O Bektas, Daniela E Oprea-Lager, Elisabeth G E de Vries, Andor W J M Glaudemans, Philippe Aftimos, Géraldine Gebhart, Andrew P Beelen, Robert C Schuit, Albert D Windhorst, Ronald Boellaard, C Willemien Menke-van der Houven van Oordt*

*Corresponding author for this work

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Abstract

PURPOSE: Positron emission tomography (PET) with 16α-[18F]-fluoro-17β-estradiol ([18F]FES) allows assessment of whole body estrogen receptor (ER) expression. The aim of this study was to investigate [18F]fluorodeoxyglucose ([18F]FDG) and [18F]FES PET/CT imaging for response prediction and monitoring of drug activity in patients with metastatic ER+ breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant.

PATIENTS AND METHODS: In this trial (NCT03455270), PET/CT imaging was performed at baseline ([18F]FDG and [18F]FES), during treatment and at time of progression (only [18F]FES). Visual, quantitative and mutational analysis was performed to derive a heterogeneity score (HS) and assess tracer uptake in lesions, in relation to the mutation profile. The primary outcome was progression-free survival (PFS).

RESULTS: The HS and PFS in the entire group did not correlate (n=16, Spearman's rho, P=0.06), but patients with a low HS (<25.0%, n=4) had a PFS of >5 months whereas patients with no [18F]FES uptake (HS 100.0%, n =3) had a PFS of <2 months. [18F]FES uptake was not affected by ESR1 mutations. On-treatment [18F]FES PET/CT scans showed no [18F]FES uptake in any of the baseline [18F]FES positive lesions. At progression, [18F]FES uptake remained blocked in patients scanned ≤1-2 half-lives of rintodestrant whereas it restored in patients scanned ≥5 days after end of treatment.

CONCLUSION: Absence of ER expression on [18F]FES PET is a predictor for no response to rintodestrant. [18F]FES uptake during treatment and at time of progression is useful to monitor the (reversible) effect of therapy and continued mode of action of SERDs.

Original languageEnglish
Pages (from-to)2075–2084
Number of pages37
JournalClinical Cancer Research
Volume29
Issue number11
Early online date3-Feb-2023
DOIs
Publication statusPublished - 1-Jun-2023

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