Aspects of 6-[¹⁸F]fluoro-L-DOPA preparation: Deuterochloroform as a substitute solvent for Freon 11

Aim:

Replacement of the ecologically harmful solvent Freon 11 (CFCl₃) by chloroform for the module-assisted preparation of 6-[¹⁸F]fluoro-L-DOPA based on the electrophilic radiofluorodestannylation of the precursor N-formyl-3,4-di-tert-butoxycarbonyloxy-6-(trimethylstannyl)-L-phenylalanine ethyl ester.

Materials and methods:

The TRACERlab Fx _FDOPA module (GE Medical Systems) was used for the preparation of 6-[¹⁸F]fluoro-L-DOPA. Cyclotron-produced [¹⁸F]F₂ gas (5 GBq) was passed through a cooled solution (5°C) of the stannyl precursor (45 mg) in CDCl₃ (10 ml). After the [¹⁸F]fluorination step, HCl (2 ml, 6 M) was added to the solution. Then the reaction mixture was heated at 80°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°C for 8 min. After cooling to 20°C the reaction mixture was purified by HPLC with two polymer-based RP columns (PRP 1, 7 μm, 10×250 mm, Hamilton) using a solution of AcOH/AcONa (pH 4.7) as eluent. The [¹⁸F]fluoro-L-DOPA fraction was collected and sterile filtrated.

Results:

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 [¹⁸F]fluoro-L-DOPA purified by HPLC was obtained in decay-corrected radiochemical yields of 25±3%, ready for human use.

Conclusion:

CDCl₃ has proved to be a convenient solvent for the module-assisted preparation of 6-[¹⁸F]fluoro-L-DOPA. In this way the use of the polluting Freon 11 can be avoided.