RPRD | A Fast and Simple Synthesizing Method of 18F-Flumazenil as Derivative …

Yong-Hyun Cho*, Hyung Woo Kim, Ki-Young Hwang, Jin-Koon Lim, Hong-Jae Lee, Jae-Ryong Woo, Hyun-Ju Kim

Pet center, Nuclear Medicine, Seoul National University Hospital, Seoul, Korea

Purpose

Department of Nuclear Medicine in Seoul National University Hospital (SNUH) had developed 18F-Flumazenil 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.

Materials and Methods

Old method : Radioactivity was produced by cyclotron was captured by QMA cartridge that had activated with 0.5M K2CO3 and water. Captured radioactivity was eluted into the reaction vial by using 0.8 mL kryptofix solution and go. After evaporation of eluent, the azeotrophic drying step repeated two times. 10 mg tosylflumazenil in 4 mL anhydrous Acetonitrile was added to a reaction vial while bubbling at 85℃. The reaction mixture was bubbling for 20 minutes and evaporating 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 2 mL HPLC loop by hand and purified 18F-Flumazenil by HPLC column. New method : We used 0.8 mL TBAB solution as a eluent. After the eluent was evaporated, 6.25 mg tosylflumazenil in 2.5 mL anhydrous acetonitrile was added to a reaction vial and the reaction mixture was bubbled for 15 minutes at 85℃. It was evaporated until the mixture volume became 0.5 mL. It was loaded to the 2 mL HPLC loop by automatic injector.

Results

In old method, FFMZ was synthesized via 6 steps synthesis procedure in 105 minutes with 30 ~ 35 % synthesizing yield (non-decay correction) and specific activity was about 0.5~2 x 105 Ci/mole. In new method, It has 3 steps synthesis procedure in 53 minutes with 40 ~ 45 % synthesizing yield and specific activity was about 3~8 x 105 Ci/mole.

Conclusion

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. But as we used to automatic injector, we can sharply decrease expose time.

Key words: 18F-Flumazenil, Benzodiazepine receptor, tosylflumazenil, synthesis method