title: Evaluation of the binding characteristics of [18F]fluoroproxyfan in the rat brain for in vivo visualization of histamine H3 receptor.
abstract: Histamine H3 receptors play an important role in biological functions. The aim of this research was to examine whether histamine H3 receptors can be visualized in vivo and in vitro with [18F]3-(1H-imidazol-4-yl)propyl 4-fluorobenzyl ether (fluoroproxyfan). [18F]Fluoroproxyfan was synthesized with high specific activity using [18F]benzyl bromide. The binding of [18F]fluoroproxyfan to rat brain homogenates was higher in the striatum and thalamus and was lowest in the cerebellum. The in vitro autoradiographic study successfully demonstrated the specific binding of [18F]fluoroproxyfan to the H3 receptor in the rat brain. In accordance with the in vitro bindings, the in vivo distribution of [18F]fluoroproxyfan was heterogeneous in the rat brain. In the blocking experiments, the heterogeneous distribution disappeared in the presence of large amounts of fluoroproxyfan. These data suggest that [18F]fluoroproxyfan can be potentially useful to image histamine H3 receptor noninvasively in the human brain by positron emission tomography.
authors.affiliation: Department of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai 980-8578, Japan. zen@cyric.tohoku.ac.jp
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Funaki
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Sato
authors.forename: Motohisa
authors.initials: M
authors.lastname: Kato
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Ren
authors.initials: R
authors.lastname: Iwata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D007093:Imidazoles / Q000737:chemistry / Q000493:pharmacokinetics*; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D007093:Imidazoles; D019275:Radiopharmaceuticals; D018100:Receptors, Histamine H3; C526998:fluoroproxyfan