¹⁸F-L-FDOPA Automated Production via the Nucleophilic Route

Objectives ¹⁸F-L-FDOPA (FDOPA) is a diagnostic tracer used in the imaging of Parkinson disease, head and neck cancers and, most recently, Neuroendocrine Tumors (NET). The aim of this work is to describe the fully automated synthesis of FDOPA on IBA’s Synthera^® platform via the nucleophilic method.

Methods The process, based on the nucleophilic method developed by Coenen et al [1] using the new non-carrier-added precursor (ABX 1336), takes place within a disposable cassette (IFP). The synthesis includes trapping of the fluoride/elution/drying, nucleophilic ¹⁸F-fluorination, oxidation of the intermediate and hydrolysis. The purification is carried out in a set of cartridges and the final product is formulated in citrate buffer.

Results The trapping of the ¹⁸F on the anion exchange cartridge, its elution with Tetrabutylammoniumhydrogen carbonate (TBA) solution followed by azeotropic drying and fluorination of the precursor in DMSO are accomplished on the first IFP (Figure 1). The intermediate compound is then purified on a reversed-phase cartridge and eluted with m-Chloroperoxybenzoic acid (m-CPBA) in acetonitrile to the second IFP, where the oxidation takes place at 60°C for 20 min. The hydrolysis is performed with HCl at 40°C. The crude mixture is diluted with the citrate buffer (pH 4.5-5.5) and purified via solid phase extraction. Total synthesis time is < 90 minutes and the quality control is within Eur. Pharmacopoeia limits.

Conclusions Reproducible and reliable FDOPA production via the nucleophilic route is achieved on commercial automated synthesizer resulting in final product of high radiochemical and chemical purity (> 95%) and high enantiomeric purity (> 98%) with n.d.c. yields > 10%.