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

Estrogen receptors (ER) are implicated in psychiatric disorders. We assessed if ER availability in the human brain could be quantified using 16α-[¹⁸F]-fluoro-17β-estradiol ([¹⁸F]FES) positron emission tomography (PET).

Seven post‑menopausal women underwent a dynamic [¹⁸F]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.

The reversible two-tissue compartment model (2T4k) model with fixed K₁/k₂ 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.

The optimal quantification method for [¹⁸F]FES was the 2T4k with fixed K₁/k₂ or Logan graphical analysis, but specific binding was only observed in the pituitary gland.