Full Automated Synthesis of ¹⁸F-FDOPA and Preliminary PET/CT Imaging

¹⁸F-fluoro-L-dihydroxyphenylalanine (¹⁸F-FDOPA) as a dopamine neurotransmitter imaging agent has been widely used for diagnosis and therapy evaluation of Parkinson's disease, brain tumors and neuroendocrine diseases with positron emission tomography (PET) imaging in clinical setting and research. To meet the increasing clinical demand in oncology and neurology, a routine protocol for the automated synthesis of ¹⁸F-FDOPA with a disposable cassette system on an imported multifunctional synthesizer was studied and discussed. ¹⁸F-FDOPA was automatically synthesized via a multiple-step reaction, including fluorination, reduction, iodization alkylation and hydrolysis, following purification by using a semi-preparative high-performance liquid chromatography (HPLC) system which was built in the multifunctional synthesizer. After HPLC purification, the purified ¹⁸F-FDOPA solution was collected and passed through a sterilizing filter into a collection bottle. The final ¹⁸F-FDOPA injection was obtained for quality control (QC) determination. The QC indexes of the final products were detected： the injection was colorless and transparent, pH value was at 4 to 5.5, radiochemical purity >98%, radionuclide purity >99%, specific activity >1.9 GBq/μmol, K_2.2.2 content <50 mg/L, methanol content <0.01%, alcohol content <0.01%, dichloromethane content <0.01 mg/L, dimethylformamide content <15 mg/L, bacterial endotoxin test <0.100 EU/mL, sterility test 0 cfu/mL,and abnormal toxicity test was negative. PET/CT imaging of rats was performed by intravenous injection of ¹⁸F-FDOPA half an hour after the intraperitoneal injection of carbidopa, PET/CT scan was performed after 100 min post-injection. The imaging of ¹⁸F-FDOPA showed symmetry high uptake in the bilateral striatum of normal rats. The decay-corrected radiochemical yield of ¹⁸F-FDOPA from the ¹⁸F-fluoride was (63.1±3.8)% (n=10) at the end of synthesis (EOS), the radiochemical purity was no less than 98%, and the total radiosynthesis time was within 80 min. The quality control results demonstrated that the quality indexes of the final injection solution met the relevant requirements of radiopharmaceutlcals, which were well-suited for clinical application. An efficient and high reproducible automatic method for the radiosynthesis of ¹⁸F-FDOPA with high radiochemical yields and good radiochemical purity is obtained and performed via a multi-step reaction on the multifunctional synthesizer. ¹⁸F-FDOPA can be used for animal and human PET imaging.