Improved work-up procedure for the production of [(18)F]flumazenil and first results of its use with a high-resolution research tomograph in human stroke.
BACKGROUND
The central benzodiazepine receptor (cBZR)-gamma-aminobutyric acid (GABA(A)) receptor complex in the human brain plays an important role in many neurological and psychiatric disorders. (18)F-Labeled flumazenil ([(18)F]FZ) provides a potentially useful tracer to investigate those disorders by means of positron emission tomography (PET).


METHODS
[(18)F]Flumazenil was synthesized from its nitro-precursor Ro 15-2344 in DMF at high temperatures between 150 degrees C and 160 degrees C. Other solvents like acetonitrile and dimethylsulfoxide were also investigated as reaction media. A new HPLC method for the final purification of [(18)F]FZ was developed to circumvent some difficulties associated with a previously published procedure sometimes led to a contamination of [(18)F]FZ with Ro 15-2344. The final purification of the radiotracer was achieved using a Waters Symmetry Prep C18 HPLC column with elution with 0.05 M sodium acetate (NaOAc) buffer (pH 5)/THF/MeOH (80:10:10).


RESULTS
[(18)F]FZ could be synthesized in reproducible radiochemical yields (RCYs) of 15-20% (decay corrected to EOB) after 80 min overall synthesis time. The synthesized [(18)F]FZ was applied for the first time in a human PET study in a patient with ischemic right middle cerebral artery stroke using the HRRT high-resolution research scanner (Siemens Medical Solution, Knoxville, TN, USA).


CONCLUSIONS
[(18)F]FZ is a potentially useful GABA receptor-binding PET ligand. A modified procedure for its preparation in reproducibly high radiochemical yields has been described and the [(18)F]FZ thus produced has been used successfully in a pilot clinical study.
Massaweh
Gassan
G
McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Schirrmacher
Esther
E
la Fougere
Christian
C
Kovacevic
Miriam
M
Wängler
Carmen
C
Jolly
Dean
D
Gravel
Paul
P
Reader
Andrew J
AJ
Thiel
Alexander
A
Schirrmacher
Ralf
R
D002545:Brain Ischemia / Q000150:complications; D005442:Flumazenil / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D011854:Radiochemistry
D005462:Fluorine Radioisotopes; D005442:Flumazenil