Movement Disorders zyxwvutsrqponm Vol. 10, No. 3, zyxwvutsrqponm 1995,.pp. 298-304 zyxwvutsrqpon 0 zyxwvutsrq 1995 Movement Disorder Society A Probe for Intracerebral Aromatic Amino-Acid Decarboxylase Activity: Distribution and Kinetics of z [ IsF]6-fluoro-~-m-Tyrosine in the Human Brain Claude Nahmias, Lindi Wahl, Raman Chirakal, Gunter Firnau, and E. Stephen Garnett Department of Nuclear Medicine, McMaster University Medical Centre, Hamilton, Ontario, Canada Summary: Positron tomography, using ['8F]6-fluoro-~-dopaas 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 ['sF16-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. Re- duced 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. Anal- ysis of plasma samples for labeled metabolites zyxwv 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 decarbox- ylation rate constant (k2J was found to be 0.0108 min-'. Because the periph- eral metabolism of FmT is simpler than that of ['8F]6-fluoro-~-dopa, we pro- pose FmT as a superior agent with which to study intracerebral dopamine metabolism in health and disease in humans. Key Words: Fluoro-meta- tyrosine-Compartmental analysis-Aromatic amino acid decarboxylase ac- tivity-Positron tomography. Positron tomography has been used to study do- pamine metabolism in humans and so gain new in- sights into Parkinson's disease (1,2), To study the integrity of the dopaminergic pathway in humans, a labeled analogue of p-tyrosine would ideally be used. However, once p-tyrosine has crossed the blood-brain barrier, it is incorporated mostly into proteins or converted to dopamine by the sequential action of tyrosine hydroxylase and aromatic amino acid decarboxylase (AADC). Para-tyrosine, labeled with '*F in the 2- position, is almost quantitatively Accepted November 20, 1994. Address correspondence and reprint requests to Dr. C. Nahmias at Department of Nuclear Medicine, McMaster Uni- versity Medical Centre, 1200 Main Street West, Hamilton, On- tario, Canada L8N 325. incorporated into proteins in the brain (3) and there- fore cannot be used to study dopamine metabolism in vivo. An alternative approach has been to use labeled analogs of dopa to study the dopamine path- way during life zyxw (43, although it is recognized that this approach bypasses the rate-limiting hydroxyl- ation step in dopamine synthesis and depends solely on the activity of AADC. Unfortunately, the use of ['8F]6-fluoro-~-dopa (F- dopa) with positron tomography to quantitate stri- atal AADC activity is complicated by the presence of methylated metabolites of F-dopa. These are formed in peripheral organs and the red blood cells. They are carried into the brain by the large neutral amino acid transport mechanism and contribute to the radioactivity measured by the tomograph (6,7). 298