In vivo imaging of brain estrogen receptors in rats: a 16α-18F-fluoro-17β-estradiol PET study.

UNLABELLED The steroid hormone estrogen is important for brain functioning and is thought to be involved in brain diseases, such as Alzheimer disease and depression. The action of estrogen is mediated by estrogen receptors (ERs). To understand the role of estrogens in brain functioning, it is important to study ERs in the brain. The aims of the present study were to determine whether ERs could be measured in the rat brain by PET with the ER ligand 16α-(18)F-fluoro-17β-estradiol ((18)F-FES) and to evaluate whether tracer uptake was affected by endogenous estrogen. METHODS Small-animal PET was used to determine (18)F-FES uptake in female rats in the diestrous phase of the estrous cycle, the proestrous phase, and after ovariectomy. Coinjection of (18)F-FES with 17β-estradiol was performed to determine whether tracer binding was specific for ERs. Additionally, (18)F-FES uptake was quantified with kinetic modeling in female rats in the proestrous phase and after ovariectomy and in male rats. RESULTS The highest levels of uptake of (18)F-FES were found (in descending order) in the pituitary, hypothalamus, bed nucleus of the stria terminalis, and amygdala. Other brain regions showed low levels of brain uptake. The level of (18)F-FES uptake was higher in the pituitary and hypothalamus in rats after ovariectomy than in rats in the proestrous phase. Coinjection with 17β-estradiol resulted in a decrease in (18)F-FES uptake in the pituitary and hypothalamus. The volume of distribution and binding potential determined with kinetic modeling were higher in the pituitary than in the other brain regions in all 3 groups. No differences were found among the groups. CONCLUSION (18)F-FES PET imaging of ER availability in the rat brain is feasible for brain regions with high ER densities.