A PROBE FOR INTRACEREBRAL AROMATIC AMINO-ACID DECARBOXYLASE ACTIVITY - DISTRIBUTION AND KINETICS OF [F-18] 6-FLUORO-L-M-TYROSINE IN THE HUMAN BRAIN

Positron tomography, using [F-18]6-fluoro-L-dopa as a tracer, has been used for the study of Parkinson's disease. Unfortunately, the analysi s of data obtained with this agent is bedeviled because it readily for ms labeled methylated metabolites that enter the brain. We have evalua ted [F-18]6-fluoro-L-m-tyrosine (FmT) as an alternative tracer to stud y intracerebral dopamine metabolism with positron tomography. Imaging studies in humans showed specific accumulation of this tracer in the d opamine-rich striatal regions. Reduced striatal uptake of the tracer w as demonstrated in a patient suffering from Parkinson's disease. Incre ased retention of the tracer was demonstrated in a subject pretreated with the peripheral decarboxylase inhibitor carbidopa. Analysis of pla sma samples for labeled metabolites of FmT revealed no methylated meta bolites. Results of compartmental analysis showed that a two-compartme nt three rate constant model described adequately the time course of r adioactivity in the striatum after an injection of FmT. The FmT decarb oxylation rate constant (k(21)) was found to be 0.0108 min(-1). Becaus e the peripheral metabolism of FmT is simpler than that of [F-18]6-flu oro-L-dopa, we propose FmT as a superior agent with which to study int racerebral dopamine metabolism in health and disease in humans.