Assessment of Human Biodistribution and Dosimetry of 4-Fluoro-11β-Methoxy-16α-18F-Fluoroestradiol Using Serial Whole-Body PET/CT

4-Fluoro-11β-methoxy-16α-18F-fluoroestradiol (4FMFES) is a newly developed radiolabeled estradiol analog for PET imaging of estrogen receptors (ERs) that shows improved target-to-background ratios, compared with 16α-18F-fluoroestradiol (FES), in small-animal models. The aim of this study was to assess the biodistribution, dosimetry, and safety of 4FMFES in healthy women. Methods: Ten healthy subjects (6 pre- and 4 postmenopausal women) who had fasted were injected with 66–201 MBq of 4FMFES at a high effective specific activity (median, 251 GBq/μmol). During a 2-h period, each subject underwent 4 serial rapid PET acquisitions and 2 low-dose CT acquisitions on a PET/CT camera. Volumes of interest were drawn over source organs for each PET acquisition, allowing the calculation of time–activity curves, residence times, and radiation dosimetry estimates. Serial blood samples were obtained to measure blood and plasma activity clearance. 4FMFES safety was assessed by blood and urine analyses and vital-sign monitoring. Results: A 4FMFES injection was well tolerated in all subjects. The liver showed high uptake, and the hepatobiliary excretion was massive. Little urinary excretion occurred. Uterus uptake was visualized in all subjects and remained relatively constant over time (maximum and mean standardized uptake values at 60 min were 5.34 ± 3.32 and 2.68 ± 1.89, respectively). Background activity was low and decreased over time, resulting in an increasing uterus-to-background ratio (12.1 ± 2.2 at 60 min). The critical organ was the gallbladder (0.80 ± 0.51 mGy/MBq), followed by the upper large intestine (0.13 ± 0.04 mGy/MBq), small intestine (0.12 ± 0.04 mGy/MBq), and liver (0095 ± 0.019 mGy/MBq). For a typical 4FMFES dose of 185 MBq, the effective dose was calculated at 4.82 ± 0.70 mSv. Conclusion: 4FMFES is considered safe for use in humans, and its effective dose remains well within acceptable limits. The absorbed dose to the gallbladder was relatively high and could potentially be reduced by injecting 4FMFES in patients who had not fasted. 4FMFES showed a significant, potentially estrogen receptor–mediated uterus uptake in both pre- and postmenopausal subjects.