Synthesis and Biodistribution of Flumazenil Derivative F-18(3-(2-Fluoro) flumazenil for Imaging Benzodiazepine Receptor.
- Author:
Sung Hyun HONG
;
Jae Min JEONG
;
Young Soo CHANG
;
Dong Soo LEE
;
June Key CHUNG
;
Jung Hyuck CHO
;
Sook Ja LEE
;
Sam Sik KANG
;
Myung Chul LEE
- Publication Type:Original Article
- Keywords:
PET;
Benzodiazepine receptor
- MeSH:
Animals;
Benzodiazepines*;
Brain;
Ethanol;
Flumazenil*;
Injections, Intravenous;
Mice;
Receptors, GABA-A*
- From:Korean Journal of Nuclear Medicine
1999;33(6):527-536
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Radiotracers that bind to the central benzodiazepine receptor are useful for the investigation of various neurological and psychiatric diseases. [C-11]Flumazenil, a benzodiazepine antagonist, is the most widely used radioligand for central benzodiazepine receptor imaging by PET. We synthesized 3-(2-[F- 18]fluoro)flumazenil, a new fluorine-18 (t1/2=110 min) labeled analogue of benzodiazepine receptor imaging agent, and evaluated in vivo for biodistribution in mice. MATERIALS AND METHODS: Flumazenil (Ro 15-1788) was synthesized by a modification of the reported method. Precursor of 3-(2-[F-18]fluoro)flumazenil, the tosylated flumazenil derivative was prepared by the tosylation of the ethyl ester by ditosylethane. [F-18] labeling of tosyl substitued flumazenil precursor was performed by adding F-18 ion at 85 degree C in the hot cell for 20 min. The reaction mixture was trapped by C18 cartridge, washed with 10% ethanol, and eluted by 40% ethanol. Bidistribution in mice was determined after intravenous injection. RESULTS: The total chemical yield of tosylated flumazenil derivative was ~40%. The efficiency of labeling 3-(2-[F-18]fluoro)flumazenil was 66% with a total synthesis time of 50 min. Brain uptakes of 3-(2-[F-18]fluoro)flumazenil at 10, 30, 60 min after injection, were 2.5+/-0.37, 2.2+/-0.26, 2.1+/-0.11 and blood activities were 3.7+/-0.43, 3.3+/-0.07, 3.3+/-0.09%ID/g, respectively. CONCLUSION: We synthesized a tosylated flumazenil derivative which was successfully labeled with no-carrier-added F-18 by nucleophilic substitution.
