The fate of perfluoro-tagged metabolites of L-DOPA in mice brains

Sherry Dingman, David Mack, Sara Branch, Rhys Thomas, Congyuan Guo, Craig A. Branch

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A novel compound for use in magnetic resonance (MR) imaging was created by covalently bonding multiple 19F atom tags to L-DOPA. Tagging L-DOPA permits bypassing the rate-limiting factor in the biosynthesis of dopamine (DA), the conversion of tyrosine into L-DOPA. The next step in the biosynthetic pathway, the removal of the carboxyl group on the molecule by the enzyme L-aromatic acid decarboxylase (AADC), happens rapidly after L-DOPA is taken up into neurons. In order to be useful as a tool in MR imaging, the novel compound and/ or its perfluoro-tagged metabolites must accumulate in vesicles in dopaminergic neurons. We administered L-DOPA with a nine 19F atom tag (250 mg/kg) to mice pups, waited 1.5 or 3 hr, and used high pressure liquid chromatography (HPLC) to examine neural tissue samples for tagged L-DOPA and tagged DA. The isomer of L-DOPA with the tag bonded at the 5 position yielded the highest conversion to tagged DA at 1.5 hr after an i.p. injection. This study provides the first direct evidence that L-DOPA, tagged with nine fluorine atoms, is taken up into mammalian brain dopaminergic neurons where it is converted to perfluro-tagged DA. The use of these tagged compounds may make it feasible to investigate the uptake and conversion of important neurotransmitter in vivo with fluorine imaging.

Original languageEnglish (US)
Pages (from-to)359-370
Number of pages12
JournalJournal of Immunoassay and Immunochemistry
Volume25
Issue number4
DOIs
StatePublished - 2004
Externally publishedYes

Fingerprint

Metabolites
Dopamine
Brain
Neurons
Fluorine
Dopaminergic Neurons
Magnetic resonance
Imaging techniques
Atoms
Magnetic Resonance Imaging
High pressure liquid chromatography
Carboxy-Lyases
Biosynthesis
Biosynthetic Pathways
Carboxylic acids
Isomers
Neurotransmitter Agents
Tyrosine
High Pressure Liquid Chromatography
Tissue

Keywords

  • DOPA
  • Dopamine
  • Fluorine imaging
  • HPLC
  • Mice
  • Neurotransmitter

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

The fate of perfluoro-tagged metabolites of L-DOPA in mice brains. / Dingman, Sherry; Mack, David; Branch, Sara; Thomas, Rhys; Guo, Congyuan; Branch, Craig A.

In: Journal of Immunoassay and Immunochemistry, Vol. 25, No. 4, 2004, p. 359-370.

Research output: Contribution to journalArticle

Dingman, Sherry ; Mack, David ; Branch, Sara ; Thomas, Rhys ; Guo, Congyuan ; Branch, Craig A. / The fate of perfluoro-tagged metabolites of L-DOPA in mice brains. In: Journal of Immunoassay and Immunochemistry. 2004 ; Vol. 25, No. 4. pp. 359-370.
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