The fate of perfluoro-tagged metabolites of L-DOPA in mice brains.
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.
Dingman
Sherry
S
Marist College, Poughkeepsie, New York 12601, USA. sherry.dingman@marist.edu
Mack
David
D
Branch
Sara
S
Thomas
Rhys
R
Guo
Congyuan
C
Branch
Craig
C
D000818:Animals; D000831:Animals, Newborn; D001682:Biological Availability; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism; D005461:Fluorine; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice
D005461:Fluorine; D004295:Dihydroxyphenylalanine; D004298:Dopamine