Development of microwave-based automated nucleophilic [(18)F]fluorination system and its application to the production of [(18)F]flumazenil.
BACKGROUND
This study presents the development of an automated radiosynthesis system integrating a microwave reactor and its subsequent application in the synthesis of [(18)F]flumazenil, a potentially useful compound in the evaluation of central benzodiazepine receptor density.


METHODS
Preparation of dry [K/K(222)](+18)F(-) complex and radiofluorination of the nitro-flumazenil precursor were achieved using the developed microwave-based radiosynthesis system. The crude product was prepurified in a C18 cartridge followed by reversed-phase preparative high-performance liquid chromatography. The isolated [(18)F]flumazenil was evaporated in vacuo and reconstituted in an ethanol-free solution.


RESULTS
Optimum incorporation of (18)F(-) in the nitro-precursor was achieved in 5 min time utilizing 2 mg of precursor in N,N-dimethylformamide reacted at 160 degrees C which gave an incorporation yield of 40+/-5%. The radiochemical yield obtained at the end of synthesis was 26+/-4% (EOB) with a radiochemical purity of >99% and a total synthesis time of about 55-60 min. The produced [(18)F]flumazenil was observed to be stable for at least 8 h.


CONCLUSIONS
The developed [(18)F]flumazenil radiosynthesis system offers shorter reaction time, simplicity in operation and applicability for use in routine clinical practice.
Mandap
Katheryn S
KS
Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193, Japan.
Ido
Tatsuo
T
Kiyono
Yasushi
Y
Kobayashi
Masato
M
Lohith
Talakad G
TG
Mori
Tetsuya
T
Kasamatsu
Shingo
S
Kudo
Takashi
T
Okazawa
Hidehiko
H
Fujibayashi
Yasuhisa
Y
D000818:Animals; D001331:Automation; D000431:Ethanol / Q000737:chemistry; D005442:Flumazenil / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D054879:Halogenation; D006358:Hot Temperature; D007267:Injections; D008297:Male; D008872:Microwaves; D049268:Positron-Emission Tomography; D051381:Rats; D012995:Solubility; D012996:Solutions; D012997:Solvents / Q000737:chemistry; D013194:Staining and Labeling
D005462:Fluorine Radioisotopes; D012996:Solutions; D012997:Solvents; D000431:Ethanol; D005442:Flumazenil