Biological evaluation of 2'-[18F]fluoroflumazenil ([18F]FFMZ), a potential GABA receptor ligand for PET.
[(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.
Mitterhauser
Markus
M
Institute for Brain Research, University of Vienna, and Hospital Pharmacy of the General Hospital, Austria. markus.mitterhauser@akh-wien.ac.at
Wadsak
Wolfgang
W
Wabnegger
Leila
L
Mien
Leonhard-Key
LK
Tögel
Stefan
S
Langer
Oliver
O
Sieghart
Werner
W
Viernstein
Helmut
H
Kletter
Kurt
K
Dudczak
Robert
R
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
C483765:2'-fluoroflumazenil; D005462:Fluorine Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D005442:Flumazenil