SYSTEMIC AND CEREBRAL KINETICS OF 16-ALPHA[F-18]FLUORO-17-BETA-ESTRADIOL - A LIGAND FOR THE IN-VIVO ASSESSMENT OF ESTROGEN-RECEPTOR BINDINGPARAMETERS

Estrogen receptors are expressed in several brain areas of various ani mal species, and steroid hormones exert physiologic and biochemical ef fects on the central nervous system. The aim of the present study was to evaluate in female adult rats, the suitability of 16 alpha[F-18]flu oro-17 beta-estradiol ([F-18]FES), a selective estrogen receptor ligan d, for the in vivo assessment of brain estrogen receptors, This was co nsidered to be a preliminary step in evaluating the potential usefulne ss of [F-18]FES for studies of cerebral estrogen receptors with positr on emission tomography (PET) in nonhuman primates and human subjects. We evaluated (a) the time course of the metabolic degradation of [F-18 ]FES in blood; Cbf the time course of distribution of the tracer in di screte cerebral areas; (c) the inhibitory effect of increasing doses o f cold estradiol on cerebral [F-18]FES uptake; and (d) the possibility of in vivo quantification of estrogen receptor binding parameters usi ng both equilibrium and dynamic kinetic analyses. We quantified [F-18] FES binding to estrogen receptors using both equilibrium and dynamic k inetic analyses. The results of this study indicate that [F-18]FES is a suitable tracer for the measurement of estrogen receptors in the pit uitary and hypothalamus, using either the equilibrium or the kinetic a nalysis. However, [F-18]FES is inadequate for the in vivo investigatio n of estrogen binding sites in brain areas with low receptor density, such as the hippocampus.