A probe for intracerebral aromatic amino-acid decarboxylase activity: distribution and kinetics of [18F]6-fluoro-L-m-tyrosine in the human brain.
Positron tomography, using [18F]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 [18F]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 two-compartment three rate constant model described adequately the time course of radioactivity in the striatum after an injection of FmT. The FmT decarboxylation rate constant (k21) was found to be 0.0108 min-1. Because the peripheral metabolism of FmT is simpler than that of [18F]6-fluoro-L-dopa, we propose FmT as a superior agent with which to study intracerebral dopamine metabolism in health and disease in humans.
Nahmias
C
C
Department of Nuclear Medicine, McMaster University Medical Centre, Hamilton, Ontario, Canada.
Wahl
L
L
Chirakal
R
R
Firnau
G
G
Garnett
E S
ES
D000293:Adolescent; D000328:Adult; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000201:enzymology; D002230:Carbidopa / Q000009:adverse effects / Q000627:therapeutic use; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000201:enzymology; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000201:enzymology; D011877:Radionuclide Imaging; D012016:Reference Values; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D005462:Fluorine Radioisotopes; C080704:6-fluoro-3-tyrosine; D014443:Tyrosine; D001142:Aromatic-L-Amino-Acid Decarboxylases; D002230:Carbidopa; D004298:Dopamine