Fastlab cassette-based automated production of [18F]FDOPA

1202 Introduction: Radiotracer 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine ([18F]FDOPA) is widely used for PET imaging of dopamine metabolism in several diseases including Parkinson’s Disease, brain tumor, neuroendocrine tumors, and focal hyperinsulinism of infancy, especially, [18F]FDOPA has been approved by US FDA in 2019 for detection of dopaminergic nerve terminals in the striatum in adult patients with suspected Parkinsonian Syndromes. A high-yield automated method for routine GMP-compliant [18F]FDOPA production is desired to meet increasing clinical need. In this study, we reported a cassette-based automated production of [18F]FDOPA in GE Fastlab 2 module and the quality control testing under fully cGMP compliant environment. Methods: Automated production of [18F]FDOPA was processed via nucleophilic radio-fluorination using FDOPA cassette (ABX, Germany) and purified via solid phase extraction. Specifically, [18F]fluoride was delivered directly into the FASTlab unit, trapped on an anion exchange cartridge (QMA), eluted with TBAHCO3, and followed by azeotropic drying. Radiofluorination of the precursor in DMSO was achieved by heating at 130°C for 8 minutes to form intermediate compound, which was purified on a C18 EC cartridge, oxidized by m-CPBA oxidation, and hydrolyzed with 30% HCl. The yielded product was further purified via C18 Sep-Pak and HR-P cartridges separation. The [18F]FDOPA product was then eluted from the cartridges with a phosphate buffer solution, and passed through a WAX cartridge, a Light Alumina N cartridge and a sterilizing 0.22 µm filter into the product vial. The quality control (QC) tests of [18F]FDOPA, including appearance, pH, half-life, radiochemical purity and identity, enantiomeric purity, chemical impurities, molecular activity, radioactive concentration, filter integrity, endotoxin and sterility, were conducted at end of synthesis (EOS) and 8 h after EOS during the production validation runs. Results: Three consecutive batches of [18F]FDOPA were successfully completed within defined specifications. The uncorrected radiochemical yields of [18F]FDOPA were 9.3 - 9.8% with a total synthesis time of ~140 min. Both the radiochemical and enantiomeric purities of [18F]FDOPA were >99.9% and the molar activities were 2.1 - 3.9 Ci/µmole at EOS. The full QC results at EOS and 8h showed that the produced [18F]FDOPA met all the release criteria for clinical use within 8 hours of expiration time. Conclusions: The cassette-based productions of [18F]FDOPA were reliably achieved with desired radiochemical yield and high radiochemical/ enantiomeric purities and molar activity. Three production validation runs and QC results demonstrated the efficacy of method for routine clinical use.