Biodistribution of 18F-FES in patients with metastatic ER+ breast cancer undergoing treatment with Rintodestrant (G1T48), a novel selective estrogen receptor degrader.

16α-18F-fluoro-17β-estradiol (18F-FES) is a positron emission tomography (PET) tracer characterizing the expression of the estrogen receptor (ER). As therapy can interfere with the kinetics and biodistribution of 18F-FES, the aim of this study was to describe the biodistribution of 18F-FES in patients with metastatic ER+ breast cancer undergoing treatment with rintodestrant (G1T48), a novel selective ER degrader. Methods: Eight patients underwent 18F-FES PET/CT imaging at baseline, 4-6 weeks during treatment with rintodestrant (interim) and after treatment. After intravenous administration of 200 MBq (+/- 10%) 18F-FES, a 50-min dynamic PET/CT scan of the thorax was performed, followed by a whole body PET/CT scan 60 min post-injection. Blood samples were drawn for measuring whole blood and plasma activity concentration and the parent fraction of 18F-FES. Volumes of interest (VOIs) were placed in the aorta ascendens and in healthy tissues on both dynamic and whole body PET scans. Standard uptake values (SUVs) and target-to-blood ratios (TBR) were calculated. Area under the curves (AUCs) of input functions and time-activity curves were calculated as a measure of uptake in different regions. Results: 18F-FES concentration in whole blood (and plasma) significantly (P <0.05) increased at interim with median AUCs of 96.6, 116.6 and 110.3 at baseline, interim and after treatment, respectively. In ER expressing tissues, i.e. the uterus and the pituitary gland, both SUV and TBR showed high 18F-FES uptake at baseline, followed by a decrease in uptake at interim (uterus: SUV -50.6% and TBR -58.5%, pituitary gland: SUV -39.0% and TBR -48.3%) which tended to return to baseline values after treatment (uterus: SUV -21.5% and TBR -37.9%, pituitary gland: SUV -14.2% and TBR -26.0%, compared to baseline). In other healthy tissues, tracer uptake remained stable over the 3 time-points. Conclusion: The biodistribution of 18F-FES is altered in blood and in ER expressing healthy tissues during therapy with rintodestrant. This indicates that rintodestrant alters the kinetics of the tracer which could affect interpretation and quantification of 18F-FES uptake. Of note, ≥6 days after ending treatment with rintodestrant, the biodistribution returned to baseline values, consistent with recovery of ER availability after wash-out of the drug.