[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

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-positive breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant.

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).

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 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.

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.