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Review
. 2021 Mar 10;6(1):11.
doi: 10.1186/s41181-021-00126-z.

Advances in the automated synthesis of 6-[18F]Fluoro-L-DOPA

Ângela C B Neves  1 , Ivanna Hrynchak  1 , Inês Fonseca  1 , Vítor H P Alves  1 , Mariette M Pereira  2 , Amílcar Falcão  1   3 , Antero J Abrunhosa  4
Affiliations
Review

Advances in the automated synthesis of 6-[18F]Fluoro-L-DOPA

Ângela C B Neves et al. EJNMMI Radiopharm Chem. .

Erratum in

Abstract

The neurotracer 6-[18F] FDOPA has been, for many years, a powerful tool in PET imaging of neuropsychiatric diseases, movement disorders and brain malignancies. More recently, it also demonstrated good results in the diagnosis of other malignancies such as neuroendocrine tumours, pheochromocytoma or pancreatic adenocarcinoma.The multiple clinical applications of this tracer fostered a very strong interest in the development of new and improved methods for its radiosynthesis. The no-carrier-added nucleophilic 18F-fluorination process has gained increasing attention, in recent years, due to the high molar activities obtained, when compared with the other methods although the radiochemical yield remains low (17-30%). This led to the development of several nucleophilic synthetic processes in order to obtain the product with molar activity, radiochemical yield and enantiomeric purity suitable for human PET studies.Automation of the synthetic processes is crucial for routine clinical use and compliance with GMP requirements. Nevertheless, the complexity of the synthesis makes the production challenging, increasing the chance of failure in routine production. Thus, for large-scale clinical application and wider use of this radiopharmaceutical, progress in the automation of this complex radiosynthesis is of critical importance.This review summarizes the most recent developments of 6-[18F]FDOPA radiosynthesis and discusses the key issues regarding its automation for routine clinical use.

Keywords: 6-[18F]FDOPA; Automated synthesis; Nonproteinogenic amino acid; PET; Radiochemistry.

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Conflict of interest statement

The authors declared no potential conflicts of interest with respect to the authorship or publication of this article.

Figures

Fig. 1
Fig. 1
6-[18F]FDOPA, 1
Fig. 2
Fig. 2
Isotopic Exchange reaction pathway for the synthesis of 5-[18F]FDOPA, 5 (Firnau & CSG, 1973)
Fig. 3
Fig. 3
Isotopic Exchange reaction for the synthesis of 6-[18F]FDOPA 1 (Wagner et al., 2009)
Fig. 4
Fig. 4
Electrophilic synthesis of 6-[18F]FDOPA (Diksic & Farrokhzad, ; Adam & Jivan, ; Luxen et al., ; Bishop et al., ; Chaly et al., ; Namavari et al., ; Dolle et al., ; Füchtner et al., ; Füchtner & Steinbach, 2003)
Fig. 5
Fig. 5
Synthesis of 6-[18F]FDOPA 1 starting from aryltrimethylammonium precursor, using chiral auxiliaries (Lemaire et al., 1994)
Fig. 6
Fig. 6
Synthesis of in 6-[18F]FDOPA by enzymatic alkylation (Kaneko et al., 1999)
Fig. 7
Fig. 7
Catalysts. 21, 22, 23 e 24
Fig. 8
Fig. 8
Synthesis of 6-[18F]FDOPA starting from trimethylammonium veratraldehyde triflate precursor, using a cPTC strategy (Libert et al., 2013)
Fig. 9
Fig. 9
Generic structure of diaryliodonium salts
Fig. 10
Fig. 10
Diaryliodonium triflate precursor for the synthesis of 6-[18F]FDOPA by anion exchange followed by thermal decomposition (Edwards & Wirth, 2015)
Fig. 11
Fig. 11
Nickel-mediated synthesis of protected 6-[18F]fluoro-3,4-dihydroxy-L-phenylalanine (Lee et al., 2012)
Fig. 12
Fig. 12
Cooper-mediated synthesis of protected 6-[18F]fluoro-3,4-dihydroxy-L-phenylalanine (Makaravage et al., 2016)
Fig. 13
Fig. 13
Copper-mediated synthesis of protected 6-[18F]fluoro-3,4-dihydroxy-L-phenylalanine starting from an aryl boronic derivative precursor (Tredwell et al., 2014)
Fig. 14
Fig. 14
Automated multistep synthesis of 6-[18F]FDOPA by Trasis®
Fig. 15
Fig. 15
ABX method for automated synthesis of 6-[18F]FDOPA (Rene-Martin et al., 2013)
See this image and copyright information in PMC

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