HPLC-free and cassette-based nucleophilic production of [18F]FDOPA for clinical use.

Abstract

Radiotracer 3,4-dihydroxy-6-[¹⁸F]fluoro-L-phenylalanine (L-6-[¹⁸F]fluorodopa or [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. In 2019, [¹⁸F]FDOPA was approved by US FDA for detection of dopaminergic nerve terminals in the striatum of adult patients with suspected Parkinsonian Syndromes. A convenient and reliable method is desired for fully automated production of [¹⁸F]FDOPA under cGMP compliance to meet the increasing clinical need. In this study, we reported a cassette-based automated production of [¹⁸F]FDOPA using a GE Fastlab 2 module and the quality control (QC) under fully cGMP compliant environment. Briefly, automated radiosynthesis of [¹⁸F]FDOPA was processed via nucleophilic radio-fluorination using FDOPA Fastlab cassette and solid phase extraction (SPE) purification. The 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 the end of synthesis (EOS) and 8 h after EOS during the validation runs. Three consecutive productions of [¹⁸F]FDOPA were reliably achieved with desired radiochemical yield and high radiochemical/enantiomeric purities and molar activity. The uncorrected radiochemical yields of [¹⁸F]FDOPA were 9.3-9.8% with a total synthesis time of ~140 min. Both 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 8 h after EOS showed that the produced [¹⁸F]FDOPA met all release criteria for clinical use within 8 hours of expiration time. Three consecutive validation runs and QC results demonstrated the efficacy of cassette-based production of [¹⁸F]FDOPA for routine clinical use.