[18F]FDG and [18F]FES PET/CT Imaging as a Biomarker for Therapy Effect in Patients with Metastatic ERþ 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, Huseyyin O. Bektas

Research output: Contribution to journalArticleAcademicpeer-review


Purpose: PET with 16a-[ 18F]-fluoro-17b-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-positive breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant. Experimental Design: 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 ¼ 16, Spearman's rho, P ¼ 0.06), but patients with a low HS (< 25.0%, n ¼ 4) had a PFS of > 5 months whereas patients with no [ 18F]FES uptake (HS 100.0%, n ¼ 3) had a PFS of < 2 months. [ 18F]FES uptake was not affected by estrogen receptor 1 (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. Conclusions: 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 pages10
JournalClinical cancer research : an official journal of the American Association for Cancer Research
Issue number11
Early online date3 Feb 2023
Publication statusPublished - 1 Jun 2023

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