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 language | English (US) |
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Pages (from-to) | 359-370 |
Number of pages | 12 |
Journal | Journal of Immunoassay and Immunochemistry |
Volume | 25 |
Issue number | 4 |
DOIs | |
State | Published - 2004 |
Externally published | Yes |
Keywords
- DOPA
- Dopamine
- Fluorine imaging
- HPLC
- Mice
- Neurotransmitter
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Clinical Biochemistry
- Medical Laboratory Technology