Trifluoromethanesulfonic acid, an alternative solvent medium for the direct electrophilic fluorination of DOPA: New syntheses of 6-[18F]fluoro- L-DOPA and 6-[18F]fluoro-D-DOPA

Babak Behnam Azad, Raman Chirakal, Gary J. Schrobilgen

Research output: Contribution to journalArticle

Abstract

Previous work from this laboratory has shown that the direct fluorination of 3, 4-dihydroxy-phenyl-L-alanine (L-DOPA) in anhydrous HF (aHF) or BF 3/HF with F2 is an efficient method for the synthesis of 6-fluoro-L-DOPA. Since then, 18F-labeled 6-fluoro-L-DOPA ([ 18F]6-fluoro-L-DOPA) has been used to study presynaptic dopaminergic function in the human brain and to monitor gastrointestinal carcinoid tumors. This work demonstrates that the reactivity and selectivity of F2 toward L-DOPA in CF3SO3H is comparable with that in aHF. This new synthetic procedure has led to the production of [18F] fluoro-L-DOPA and [18F]fluoro-L-DOPA isomers in 17 ± 2% radiochemical yields (decay corrected with respect to [18F]F 2). The 2- and 6-FDOPA isomers were separated by HPLC and subsequently characterized by 19F NMR spectroscopy. The corresponding [18F]-FDOPA enantiomers have been obtained in clinically useful quantities by a synthetic approach that avoids the use of aHF.

Original languageEnglish (US)
Pages (from-to)1236-1242
Number of pages7
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume50
Issue number14
DOIs
StatePublished - Dec 2007
Externally publishedYes

Fingerprint

Fluorination
Halogenation
Isomers
Enantiomers
Alanine
Nuclear magnetic resonance spectroscopy
Tumors
Brain
Carcinoid Tumor
Magnetic Resonance Spectroscopy
High Pressure Liquid Chromatography
trifluoromethanesulfonic acid
fluorodopa F 18

Keywords

  • Cyclotron
  • DOPA
  • Electrophilic fluorination
  • Fluorine-18
  • PET
  • Radiolabeling

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Radiology Nuclear Medicine and imaging
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

Cite this

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title = "Trifluoromethanesulfonic acid, an alternative solvent medium for the direct electrophilic fluorination of DOPA: New syntheses of 6-[18F]fluoro- L-DOPA and 6-[18F]fluoro-D-DOPA",
abstract = "Previous work from this laboratory has shown that the direct fluorination of 3, 4-dihydroxy-phenyl-L-alanine (L-DOPA) in anhydrous HF (aHF) or BF 3/HF with F2 is an efficient method for the synthesis of 6-fluoro-L-DOPA. Since then, 18F-labeled 6-fluoro-L-DOPA ([ 18F]6-fluoro-L-DOPA) has been used to study presynaptic dopaminergic function in the human brain and to monitor gastrointestinal carcinoid tumors. This work demonstrates that the reactivity and selectivity of F2 toward L-DOPA in CF3SO3H is comparable with that in aHF. This new synthetic procedure has led to the production of [18F] fluoro-L-DOPA and [18F]fluoro-L-DOPA isomers in 17 ± 2{\%} radiochemical yields (decay corrected with respect to [18F]F 2). The 2- and 6-FDOPA isomers were separated by HPLC and subsequently characterized by 19F NMR spectroscopy. The corresponding [18F]-FDOPA enantiomers have been obtained in clinically useful quantities by a synthetic approach that avoids the use of aHF.",
keywords = "Cyclotron, DOPA, Electrophilic fluorination, Fluorine-18, PET, Radiolabeling",
author = "{Behnam Azad}, Babak and Raman Chirakal and Schrobilgen, {Gary J.}",
year = "2007",
month = "12",
doi = "10.1002/jlcr.1454",
language = "English (US)",
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pages = "1236--1242",
journal = "Journal of Labelled Compounds and Radiopharmaceuticals",
issn = "0362-4803",
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TY - JOUR

T1 - Trifluoromethanesulfonic acid, an alternative solvent medium for the direct electrophilic fluorination of DOPA

T2 - New syntheses of 6-[18F]fluoro- L-DOPA and 6-[18F]fluoro-D-DOPA

AU - Behnam Azad, Babak

AU - Chirakal, Raman

AU - Schrobilgen, Gary J.

PY - 2007/12

Y1 - 2007/12

N2 - Previous work from this laboratory has shown that the direct fluorination of 3, 4-dihydroxy-phenyl-L-alanine (L-DOPA) in anhydrous HF (aHF) or BF 3/HF with F2 is an efficient method for the synthesis of 6-fluoro-L-DOPA. Since then, 18F-labeled 6-fluoro-L-DOPA ([ 18F]6-fluoro-L-DOPA) has been used to study presynaptic dopaminergic function in the human brain and to monitor gastrointestinal carcinoid tumors. This work demonstrates that the reactivity and selectivity of F2 toward L-DOPA in CF3SO3H is comparable with that in aHF. This new synthetic procedure has led to the production of [18F] fluoro-L-DOPA and [18F]fluoro-L-DOPA isomers in 17 ± 2% radiochemical yields (decay corrected with respect to [18F]F 2). The 2- and 6-FDOPA isomers were separated by HPLC and subsequently characterized by 19F NMR spectroscopy. The corresponding [18F]-FDOPA enantiomers have been obtained in clinically useful quantities by a synthetic approach that avoids the use of aHF.

AB - Previous work from this laboratory has shown that the direct fluorination of 3, 4-dihydroxy-phenyl-L-alanine (L-DOPA) in anhydrous HF (aHF) or BF 3/HF with F2 is an efficient method for the synthesis of 6-fluoro-L-DOPA. Since then, 18F-labeled 6-fluoro-L-DOPA ([ 18F]6-fluoro-L-DOPA) has been used to study presynaptic dopaminergic function in the human brain and to monitor gastrointestinal carcinoid tumors. This work demonstrates that the reactivity and selectivity of F2 toward L-DOPA in CF3SO3H is comparable with that in aHF. This new synthetic procedure has led to the production of [18F] fluoro-L-DOPA and [18F]fluoro-L-DOPA isomers in 17 ± 2% radiochemical yields (decay corrected with respect to [18F]F 2). The 2- and 6-FDOPA isomers were separated by HPLC and subsequently characterized by 19F NMR spectroscopy. The corresponding [18F]-FDOPA enantiomers have been obtained in clinically useful quantities by a synthetic approach that avoids the use of aHF.

KW - Cyclotron

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