title: Imaging of aromatase distribution in rat and rhesus monkey brains with [11C]vorozole.
abstract: Aromatase is an enzyme that converts androgens to estrogens and may play a role in mood and mental status. The aim of this study was to demonstrate that brain aromatase distribution could be evaluated with a novel positron emission tomography (PET) tracer [(11)C]vorozole. Vorozole is a nonsteroidal aromatase inhibitor that reversibly binds to the heme domain of aromatase. In vitro experiments in rat brain, using frozen section autoradiography, illustrated specific binding in the medial amygdala (MA), the bed nucleus of stria terminalis (BST) and the preoptic area (POA) of male rat brain. Specific binding in female rat brain was found in the MA and the BST; however, the signals were lower than those of males. The K(d) of [(11)C]vorozole binding to aromatase in MA was determined to be 0.60+/-0.06 nM by Scatchard plot analysis using homogenates. An in vivo PET study in female rhesus monkey brain demonstrated the uptake of [(11)C]vorozole in the amygdala, where the uptake was blocked by the presence of excess amounts of unlabeled vorozole. Thus, this tracer has a high affinity for brain aromatase and could have a potential for in vivo aromatase imaging. This technique might enable the investigation of human brain aromatase in healthy and diseased persons.
authors.affiliation: Division of Pharmacology, Department of Neuroscience, Uppsala University, Uppsala SE-75124, Sweden. kayo.takahashi@uppsala.imanet.se
authors.forename: Kayo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Mats
authors.initials: M
authors.lastname: Bergström
authors.forename: Pernilla
authors.initials: P
authors.lastname: Frändberg
authors.forename: Eva-Lotta
authors.initials: EL
authors.lastname: Vesström
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Bengt
authors.initials: B
authors.lastname: Långström
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D008253:Macaca mulatta; D008297:Male; D008657:Metabolic Clearance Rate; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014018:Tissue Distribution; D014230:Triazoles / Q000493:pharmacokinetics*
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D014230:Triazoles; C060523:vorozole; D001141:Aromatase