Synthesis of high-molar-activity [18F]6-fluoro-l-DOPA suitable for human use via Cu-mediated fluorination of a BPin precursor
- 8 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Protocols
- Vol. 15 (5), 1742-1759
- https://doi.org/10.1038/s41596-020-0305-9
Abstract
[18F]6-fluoro-l-DOPA ([18F]FDOPA) is a diagnostic radiopharmaceutical for positron emission tomography (PET) imaging that is used to image Parkinson’s disease, brain tumors, and focal hyperinsulinism of infancy. Despite these important applications, [18F]FDOPA PET remains underutilized because of synthetic challenges associated with accessing the radiotracer for clinical use; these stem from the need to radiofluorinate a highly electron-rich catechol ring in the presence of an amino acid. To address this longstanding challenge in the PET radiochemistry community, we have developed a one-pot, two-step synthesis of high-molar-activity [18F]FDOPA by Cu-mediated fluorination of a pinacol boronate (BPin) precursor. The method is fully automated, has been validated to work well at two separate sites (an academic facility with a cyclotron on site and an industry lab purchasing [18F]fluoride from an outside vendor), and provides [18F]FDOPA in reasonable radiochemical yield (2.44 ± 0.70 GBq, 66 ± 19 mCi, 5 ± 1%), excellent radiochemical purity (>98%) and high molar activity (76 ± 30 TBq/mmol, 2,050 ± 804 Ci/mmol), n = 26. Herein we report a detailed protocol for the synthesis of [18F]FDOPA that has been successfully implemented at two sites and validated for production of the radiotracer for human use.Funding Information
- U.S. Department of Health & Human Services | National Institutes of Health (R01EB021155, R01EB021155)
- U.S. Department of Energy (DE-SC0012484)
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