Aspects of 6-[18F]fluoro-L-DOPA preparation

Abstract

Replacement of the ecologically harmful solvent Freon 11 (CFCl(3)) by chloroform for the module-assisted preparation of 6-[(18)F]fluoro-L-DOPA based on the electrophilic radiofluorodestannylation of the precursor N-formyl-3,4-di-tert-butoxycarbonyloxy-6-(trimethylstannyl)-L-phenylalanine ethyl ester. The TRACERlab Fx FDOPA module (GE Medical Systems) was used for the preparation of 6-[(18)F]fluoro-L-DOPA. Cyclotron-produced [(18)F]F(2) gas (5 GBq) was passed through a cooled solution (5 degrees C) of the stannyl precursor (45 mg) in CDCl(3) (10 ml). After the [(18)F]fluorination step, HCl (2 ml, 6 mol/l) was added to the solution. Then the reaction mixture was heated at 80 degrees C for 5 min under vacuum to evaporate the chloroform. The hydrolysis to remove the protecting groups was completed by heating the closed reactor at 130 degrees C for 8 min. After cooling to 20 degrees C the reaction mixture was purified by HPLC with two polymer-based RP columns (PRP-1, 7 microm, 10 x 250 mm, Hamilton) using a solution of AcOH/AcONa (pH 4.7) as eluent. The 6-[(18)F]fluoro-L-DOPA fraction was collected and sterile filtrated. Three types of stabilised chloroform were tested for the radiofluorination of the precursor. Only by use of deuterochloroform stabilised with silver no significant losses of radioactivity were observed. Thus, 6-[(18)F]fluoro-L-DOPA purified by HPLC was obtained in decay-corrected radiochemical yields of 25+/-3%, ready for human use. CDCl(3) has proved to be a convenient solvent for the module-assisted preparation of 6-[(18)F]fluoro-L-DOPA. In this way the use of the polluting Freon 11 can be avoided.