Systemic and Cerebral Kinetics of 16α[ 18 F]Fluoro-17β-Estradiol: A Ligand for the in vivo Assessment of Estrogen Receptor Binding Parameters

Estrogen receptors are expressed in several brain areas of various animal species, and steroid hormones exert physiologic and biochemical effects on the central nervous system. The aim of the present study was to evaluate in female adult rats, the suitability of 16α[¹⁸F]fluoro-17β-estradiol ([¹⁸F]FES), a selective estrogen receptor ligand, for the in vivo assessment of brain estrogen receptors. This was considered to be a preliminary step in evaluating the potential usefulness of [¹⁸F]FES for studies of cerebral estrogen receptors with positron emission tomography (PET) in nonhuman primates and human subjects. We evaluated (a) the time course of the metabolic degradation of [¹⁸F]FES in blood; (b) the time course of distribution of the tracer in discrete cerebral areas; (c) the inhibitory effect of increasing doses of cold estradiol on cerebral [¹⁸F]FES uptake; and (d) the possibility of in vivo quantification of estrogen receptor binding parameters using both equilibrium and dynamic kinetic analyses. We quantified [¹⁸F]FES binding to estrogen receptors using both equilibrium and dynamic kinetic analyses. The results of this study indicate that [¹⁸F]FES is a suitable tracer for the measurement of estrogen receptors in the pituitary and hypothalamus, using either the equilibrium or the kinetic analysis. However, [¹⁸F]FES is inadequate for the in vivo investigation of estrogen binding sites in brain areas with low receptor density, such as the hippocampus.