Metabolism and blood-brain clearance of l-3,4-dihydroxy-[³H]phenylalanine ([³H]DOPA) and 6-[¹⁸F]fluoro-l-DOPA in the rat

6-[¹⁸F]fluoro-l-DOPA (FDOPA) has been used as a tracer for the cerebral activity of l-3,4-dihydroxyphenylalanine (DOPA)-decarboxylase in studies of positron emission tomography (PET). However, the substitution of fluorine on the aromatic ring may alter the disposition and metabolism of FDOPA from that of endogenous DOPA. In the present study, the kinetics of the peripheral metabolism and the facilitated unidirectional blood-brain clearance of [³H]DOPA and FDOPA were compared in Wistar rats pretreated with carbidopa. In arterial plasma, FDOPA was O-methylated with an apparent rate constant (0.031 min^-1) 3-fold that of [³H]DOPA in the same rats. The O-methylated metabolite of FDOPA (OMe-FDOPA) was eliminated from plasma at a rate constant (0.018 min^-1) 3-fold that of OMe-[³H]DOPA. The mean unidirectional blood-brain clearance of FDOPA (4.5 mL · hg^-1 · min^-1) in six brain regions was 60% higher than that of [³H]DOPA.