title: Biological evaluation of 2'-[18F]fluoroflumazenil ([18F]FFMZ), a potential GABA receptor ligand for PET.
abstract: [(11)C]Flumazenil, a highly selective benzodiazepine antagonist is the most extensively used GABA(A) ligand for PET so far. To overcome half life disadvantages of (11)C a [(18)F]-labeled flumazenil derivative, 2'-[(18)F]fluoroflumazenil (FFMZ) was developed and biologically evaluated with respect to the GABA(A) receptor. Organ with the highest uptake was the pituitary gland. Brain uptake was high and followed the order cortex>thalamus>cerebellum>rest brain. Fluoroflumazenil displaced [(3)H]flumazenil binding from membrane GABA(A) receptors with an IC(50)value (3.5 nM) comparable to that of Flumazenil (2.8 nM). The presented data confirm the potential of [(18)F]FFMZ for PET imaging of the GABA-ergic system.
authors.affiliation: Institute for Brain Research, University of Vienna, and Hospital Pharmacy of the General Hospital, Austria. markus.mitterhauser@akh-wien.ac.at
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.forename: Leila
authors.initials: L
authors.lastname: Wabnegger
authors.forename: Leonhard-Key
authors.initials: LK
authors.lastname: Mien
authors.forename: Stefan
authors.initials: S
authors.lastname: Tögel
authors.forename: Oliver
authors.initials: O
authors.lastname: Langer
authors.forename: Werner
authors.initials: W
authors.lastname: Sieghart
authors.forename: Helmut
authors.initials: H
authors.lastname: Viernstein
authors.forename: Kurt
authors.initials: K
authors.lastname: Kletter
authors.forename: Robert
authors.initials: R
authors.lastname: Dudczak
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D005442:Flumazenil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D008024:Ligands; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: C483765:2'-fluoroflumazenil; D005462:Fluorine Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D005442:Flumazenil