High yield 18F-FDOPA using nucleophilic synthesis in a PET clinical study

Objectives To evaluate the high activity production of 18F-FDOPA using a cassette based nucleophilic radiosynthesis and HPLC purification using the Trasis AllinOne automated synthesizer for clinical PET imaging.

Methods 18F-Fluoride was produced in the Siemens Eclipse-HP cyclotron by bombardment of 18O-water in a tantalum target for a total of 2 hours of using dual beam irradiation. Approximately 0.5 ml of irradiated 18O-water was sent to the Trasis AllinOne automated synthesizer equipped with a commercially available cassette system and reagents for chemical synthesis where 6-nitroveratraldehyde is converted into 18F-FDOPA and purified by a reversed phase semi preparative HPLC. The 18F-FDOPA final product was tested for quality control which included chemical, radiochemical, enantiomeric and radionuclidic purity, as well as bacterial endotoxin and sterility, before release for clinical use.

Results Two hours of dual-beam irradiation produced 215 GBq of 18F-fluoride that was sent to the automated synthesizer. After 75 minutes of synthesis, over 82 GBq of 18F-FDOPA was produced, which gives an uncorrected yield of 38%. This product was stored at room temperature for 12hours and tested for stability. The product was found to be stable. The residual impurities were well under the accepted USP limits for residual solvents methanol, ethanol and dichloromethane. The product was still enantiomerically pure.

Conclusions Production of 18F-FDOPA in very high activity has always been difficult until automated synthesizer such as the Trasis AllinOne were available. Usually it has been produced using electrophilic 18F-fluorination, where stability has also been an issue. This study has demonstrated that high activity of 18F-FDOPA can be produced and that the product is stable for 12hours after production. This permits the shipments of high activity of 18F-FDOPA to the PET facilities at 5hour distance from the production facility.