Pharmacokinetic Analysis of [18F]FES PET in the Human Brain and Pituitary Gland

• Published in: Molecular imaging and biology Vol. 26; no. 2; pp. 351 - 359
• Main Authors: Ghazanfari, Nafiseh, Doorduin, Janine, van der Weijden, Chris W. J., Willemsen, Antoon T. M., Glaudemans, Andor W. J. M., van Waarde, Aren, Dierckx, Rudi A. J. O., de Vries, Erik F. J.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2024; Springer Nature B.V
• Subjects: 17β-Estradiol; Binding; Brain; Brain - metabolism; Correlation; Estradiol; Estrogen receptors; Estrogens; Female; Fluorine isotopes; Humans; Imaging; Medicine; Medicine & Public Health; Mental disorders; Metabolites; Parameter estimation; Pharmacokinetics; Pituitary; Pituitary gland; Pituitary Gland - metabolism; Positron emission; Positron emission tomography; Positron-Emission Tomography - methods; Radiology; Receptors, Estrogen - metabolism; Research Article; Sex hormones; Standard error; Neuroimaging; Estrogen receptor; Receptor density; Kinetic modeling; Positron emission tomography
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-023-01880-z

Purpose Estrogen receptors (ER) are implicated in psychiatric disorders. We assessed if ER availability in the human brain could be quantified using 16α-[ 18 F]-fluoro-17β-estradiol ([ 18 F]FES) positron emission tomography (PET). Procedures Seven post‑menopausal women underwent a dynamic [ 18 F]FES PET scan with arterial blood sampling. A T1-weighted MRI was acquired for anatomical information. After one week, four subjects received a selective ER degrader (SERD), four hours before the PET scan. Pharmacokinetic analysis was performed using a metabolite-corrected plasma curve as the input function. The optimal kinetic model was selected based on the Akaike information criterion and standard error of estimated parameters. Accuracy of Logan graphical analysis and standardized uptake value (SUV) was determined via correlational analyses. Results The reversible two-tissue compartment model (2T4k) model with fixed K 1 /k 2 was preferred. The total volume of distribution (V T ) could be more reliably estimated than the binding potential (BP ND ). A high correlation of V T with Logan graphical analysis was observed, but only a moderate correlation with SUV. SERD administration resulted in a reduced V T in the pituitary gland, but not in other regions. Conclusions The optimal quantification method for [ 18 F]FES was the 2T4k with fixed K 1 /k 2 or Logan graphical analysis, but specific binding was only observed in the pituitary gland.