Synthesis of high specific activity [18F]FDOPA using a synthesizing device with a user-configurable cassette

1812 Objectives 6-[18F]fluoro-L-DOPA ([18F]FDOPA) is a useful PET tracer for the evaluation of presynaptic dopaminergic function in diagnosis and research. [18F]FDOPA can be synthesized via electrophilic or nucleophilic routes. In recent years the nucleophilic synthesis route starting from no-career-added 18F has drawn attention of the researchers because of its high specific activity (>50 MBq/nmol), which may visualize presynaptic dopaminergic function in more detail. CFN-MPS200 (MPS200, Sumitomo Heavy Industries, Japan) is a PET drug synthesizing device for research use, in which cassettes can be designed and assembled by the user with sequence programming also being open to users, and fluoride-free materials can be used for tubes and connectors. Our previous experiments showed that specific activity of [18F]fluorothymidine (FLT) was >1000 MBq/nmol using fluoride-free materials on MPS200, while it was Methods [18F]FDOPA was synthesized with the known three-pot reaction (B. Shen et al. Appl. Radiat. Isot., 2009, 1650-1653) on MPS200 together with a solid extraction unit. The cassette for FDOPA synthesis was designed with compact and efficient routing, and the programs were developed to control the synthesis. Fluoride-free materials, such as silicon tubes and polypropylene connectors, were used for the cassette. After the synthesis of [18F]FDOPA, the product was purified by HPLC and sterilized by filtration. The quality of [18F]FDOPA was tested for conformity to the specifications of our facility. Results The specific activity was 4037 ± 1472 MBq/nmol, which is 100,000 times higher than the synthesis method via electrophilic route, and more than twice the previous reports via nucleophilic routes. This was realized by avoiding fluoride containing materials (e.g. Teflon, PTFE etc.) that would reduce the specific activity of 18F products via 18F-19F exchange. The amount of [18F]FDOPA was 4.9 ± 2.5 GBq at the end of synthesis. The synthesis time was 91 ± 8 min, and the yield was 9.1 ± 2.3% (decay corrected). The radiochemical purify (RCP) was 97 ± 2%, and the enantiomeric excess was 97 ± 3%. It is stable for more than 4 hours at room temperature (RCP >90%). The quality of [18F]FDOPA (e.g. appearance, radiochemical identity, radionuclidic identity, pH, residual solvents, bacterial endotoxin, sterility etc.) all conformed to the quality specifications. This synthesis method was approved for human use by the institutional PET drug committee and IRB, and is now used for clinical research. Conclusions In this study, we created a synthesis method of high specific activity [18F]FDOPA on the synthesizer MPS200 by developing a cassette and programs. The [18F]FDOPA had a high specific activity and sufficient quality and practicability for clinical research use. This new method of cassette and program on MPS200 provides reliable production of high specific activity [18F]FDOPA and may further be potentially developed into a commercial synthesis system.