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16α- 18 F-fluoro-17β-estradiol ( 18 F-FES) is a PET tracer characterizing the expression of the estrogen receptor (ER). Because therapy can interfere with the kinetics and biodistribution of 18 F-FES, the aim of this study was to describe the biodistribution of 18 F-FES in patients with metastatic ER-positive (ER+) breast cancer undergoing treatment with rintodestrant (G1T48), a novel selective ER degrader. Methods: Eight patients underwent 18 F-FES PET/CT imaging at baseline, 4-6 wk during treatment with rintodestrant (interim), and after treatment. After intravenous administration of 200 MBq (±10%) of 18 F-FES, a 50-min dynamic PET/CT scan of the thorax was obtained, followed by a whole-body PET/CT scan 60 min after injection. Blood samples were drawn for measuring whole blood and plasma activity concentration and the parent fraction of 18 F-FES. Volumes of interest were placed in the aorta ascendens and in healthy tissues on both dynamic and whole-body PET scans. SUVs and target-to-blood ratios (TBRs) were calculated. Areas under the curve (AUCs) of input functions and time-activity curves were calculated as a measure of uptake in different regions. Results:  18 F-FES concentration in whole blood (and plasma) significantly ( P &lt; 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, that is, the uterus and the pituitary gland, both SUV and TBR showed high 18 F-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 with baseline). In other healthy tissues, tracer uptake remained stable over the 3 time points. Conclusion: The biodistribution of 18 F-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, possibly affecting interpretation and quantification of 18 F-FES uptake. Of note, 6 d or more after treatment with rintodestrant ended, the biodistribution returned to baseline values, consistent with recovery of ER availability after washout of the drug.

the journal of nuclear medicine

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

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

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