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A probe for intracerebral aromatic amino‐acid decarboxylase activity: Distribution and kinetics of [ 18 F]6‐fluoro‐ L ‐ m ‐tyrosine in the human brain
Author(s) -
Nahmias Claude,
Wahl Lindi,
Chirakal Raman,
Firnau Gunter,
Garnett E. Stephen
Publication year - 1995
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.870100312
Subject(s) - kinetics , tyrosine , aromatic l amino acid decarboxylase , chemistry , human brain , distribution (mathematics) , biochemistry , stereochemistry , neuroscience , enzyme , biology , physics , mathematical analysis , mathematics , quantum mechanics
Positron tomography, using [ 18 F]6‐fluoro‐ L ‐dopa as a tracer, has been used for the study of Parkinson's disease. Unfortunately, the analysis of data obtained with this agent is bedeviled because it readily forms labeled methylated metabolites that enter the brain. We have evaluated [ 18 F]6‐fluoro‐ L ‐ m ‐tyrosine (FmT) as an alternative tracer to study intracerebral dopamine metabolism with positron tomography. Imaging studies in humans showed specific accumulation of this tracer in the dopamine‐rich striatal regions. Reduced striatal uptake of the tracer was demonstrated in a patient suffering from Parkinson's disease. Increased retention of the tracer was demonstrated in a subject pretreated with the peripheral decarboxylase inhibitor carbidopa. Analysis of plasma samples for labeled metabolites of FmT revealed no methylated metabolites. Results of compartmental analysis showed that a twocompartment three rate constant model described adequately the time course of radioactivity in the striatum after an injection of FmT. decarboxylation rate constant (k 21 ) was found to be 0.0108 min −1 . Because the peripheral metabolism of FmT is simpler than that of [ 18 F]6‐fluoro‐ L ‐dopa, we propose FmT as a superior agent with which to study intracerebral dopamine metabolism in health and disease in humans.