Method for preparation of fluorine-18-labeled flumazenil using diaryliodonium salt precursor
Disclosed is the synthesis of [ 18 F]flumazenil that is useful in imaging epileptic lesions by PET (positron emission tomography). A method for preparing [ 18 F]flumazenil by reacting a diaryliodonium salt precursor with the positron-emitting radionuclide fluorine-18. [ 18 F]flumazenil can be prepared from the diaryliodonium salt precursor in the presence of kryptofix 2.2.2. /potassium carbonate(K 2.2.2. /K 2 CO 3 ) and TEMPO in dimethylformamide (DMF) at a high yield.
1. A method for preparing fluorine-18-labeled flumazenil, comprising reacting a diaryliodonium salt precursor with fluorine-18 at 130 to 160° C. in the presence of a phase transition catalyst which is selected from the group consisting of kryptofix 2.2.2. /potassium carbonate (K 2.2.2. /K 2 CO 3 ), tetrabutylammonium hydroxide (TBAOH), tetrabutylammonium bicarbonate (TBAHCO 3 ), cesium hydroxide (CsOH), and a combination thereof,
wherein the diaryliodonium salt precursor is represented by the following Chemical Formula 1:
wherein Ar− is selected from the group consisting of the following aryl (Ar−) radicals:
and X − is selected from among trifluoromethane sulfonate), perfluoro C 2 -C 10 alkyl sulphonate, trifluoroacetate, tetraphenylborate), toluene sulfonate), Br − , and Cl − .
2. The method of claim 1 , wherein the reacting is carried out in the presence of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) in a reaction solvent.
3. A method for preparing fluorine-18-labeled flumazenil, comprising reacting a diaryliodonium salt precursor with fluorine-18, wherein the diaryliodonium salt precursor is represented by the following Chemical Formula 2:
wherein —Ar is
R 1 ˜R 3 independently selected from among H, C 1 alkyl, C 2 alkyl, C 1 haloalkyl, and C 2 haloalkyl, and X − is selected from among trifluoromethane sulfonate, perfluoro C 2 -C 10 alkyl sulphonate, trifluoroacetate, tetraphenylborate, toluene sulfonate, Br − , and Cl − .