Quantitative and simplified [18F] fluoroestradiol positron emission tomography (PET) measures of brain estrogen...

Positron emission tomography (PET) with 16α-[¹⁸F]fluoro-17β-estradiol (¹⁸F-FES) allows for the in vivo assessment of brain estrogen receptor (ER) expression. This study examines brain ¹⁸F-FES uptake to define an optimal acquisition time for static late images suitable for clinical application.

Fifty-five healthy, 40-65-year-old women at different endocrine aging stages (n = 18 premenopause, n = 18 perimenopause, and n = 19 postmenopause) underwent dynamic 90-minute ¹⁸F-FES PET imaging. We obtained regional brain distribution volume ratios (DVR) based on Logan graphical analysis and standardized uptake value ratios (SUVR) at five 20 min increments (30-50, 40-60, 50-70, 60-80 and 70-90 min post-injection), using the cerebellar gray matter as the reference. We used reliability analysis and automated variable selection procedures to identify the most consistent SUVR time windows relative to DVR. In sensitivity analyses, we tested for group differences and associations with cognitive performance in these SUVR time frames. Analysis focused on the pituitary gland, which has demonstrated specific binding. Exploratory ER-rich regions of interest (ROI) included hypothalamus, hippocampus, amygdala, caudate, frontal and cingulate cortex.

SUVR measurements exhibited stronger associations with DVR at earlier compared to later time frames. Specifically, the optimal SUVR time frames in pituitary, and in most exploratory ROIs, were predominantly within the 30-50 and 40-60 min intervals. Both intervals were effective at differentiating postmenopausal versus premenopausal groups, and the 30-50 min window showed more significant associations with cognitive scores.

Examination of quantitative and simplified methods for analysis of brain ¹⁸F-FES PET uptake identified the 30-60 min SUVR window as performing optimally relative to DVR measures. This provides a practical method for quantifying relative pituitary tracer retention in clinical populations.