간질 PET영상을 위한 플루마제닐(벤조디아제핀 수용체)유도체의 신속하고 간단한 합성방법 소개

A Fast and Simple Synthesizing Method of ¹⁸F-Flumazenil as Derivative Benzodiazepine Receptor for Epilepsy PET Imaging

Department of Nuclear Medicine in Seoul National University Hospital (SNUH) had developed ¹⁸FFlumazenil as Benzodiazepine receptor imaging agent for PET diagnosis of Epilepsy. But production Activity of ¹⁸F-Flumazenil is decreased owing to this method has difficult synthesis procedures and pretty long synthesis time. In this study, we can modify synthesizing method to have more simple procedure and less spend time and help to increase production Activity. Old method: Radioactivity was produced by cyclotron was captured by QMA cartridge that was activated. Captured radioactivity was eluted into the reaction vial by using kryptofix solution and delivered. After evaporation of eluent, the azeotrophic drying step repeated two times. tosylflumazenil in anhydrous Acetonitrile was added to a reaction vial while bubbling. The reaction mixture was evaporated until the mixture volume was 0.5 mL. Reaction vial washed with 20 % Acetonitrile and that solution went into the reaction vial. The reaction mixture was loaded to the HPLC loop by hand and purified ¹⁸F-Flumazenil by HPLC column. New method: We used TBAHCO3 solution as a eluent. After the eluent was evaporated, tosylflumazenil in anhydrous acetonitrile was added to a reaction vial and the reaction mixture was bubbled for 15 minutes. It was evaporated until the mixture volume became 0.5 mL. It was loaded to the HPLC loop. In old method, ¹⁸F-Flumazenil was synthesized via 6 steps synthesis procedures in 105 minutes with 30~35% synthesizing yield (non-decay correction) and specific activity was about 0.5~2×105 Ci/mole. In new method, It had 3 steps synthesis procedures in 53 minutes with 40~45% synthesizing yield and specific activity was about 3~8×105 Ci/mole. This method leads to improve of minimizing synthesis time, increasing synthesis yield and specific activity. While we can load reaction mixture to the HPLC loop, we can expose high radiation field thanks to used by hand.