RPRD | Facile synthesis of 6-[18F]FDOPA using electrophilic substitution reac…

Yong-Hyun Cho², Yun-Sang Lee¹, Jae Hyung Lee², Yong-Seok Lee², Hong-Jae Lee², Jin-Eui Kim², Keon-Wook Kang¹, Jae Min Jeong¹*

¹Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea

²Nuclear Medicine, Seoul National University Hospital, Seoul, Korea

Purpose

[18F]FDOPA has been synthesized using CFCl3 as a solvent for electrophilic substitution reaction because of high yield and convenience. However, many laboratories replaced CFCl3 with other solvents such as CHCl3, CDCl3, CH2Cl2, or CD2Cl2 since the effect of Montreal Protocol [1-3]. We tried to set up a procedure for the most simple and high yield using CDCl3 as a solvent.

Materials and Methods

We used an automated synthesizer Fx-Fn (GE, U.S.A.) for production. [18F]F2 gas was produced by 20Ne(d,α)18F reaction in the presence of 0.1% F2 gas using a cyclotron and was passed through the reaction vial containing 30 mg precursor in 1 mL CDCl3 at room temperature. After purging for 10 min, solvent was evaporated by raising temperature to 130 °C and further 30 sec purging. Hydrolysis was performed using 0.6 mL HBr (48%) at 130°C for 10 min. The reaction mixture was neutralized with 0.6 mL NH4OH (28%), and then was injected into the HPLC equipped with a semi-prep reverse phase column (Fig. 1).

Results

Synthesis time including purification was less than 35 min and final yield was 19.3 ± 3.1% (no decay corrected). Specific activity was 20.2 ± 4.6 GBq/ mmol. HPLC eluent was in 0.5% acetic acid. We added 0.5 mL 8.6% NaHCO3 to neutralize it before injection into the patients. [18F]FDOPA was stable for at least 2 h at room temperature.

Conclusion

We successfully developed a high yield, simple and fast electrophilic synthesis method for [18F]FDOPA.