In vivo brain microdialysis was used to monitor 6-[F-18]fluoro-L-m-tyr
osine (FMT) uptake and metabolism in the striatum of conscious freely
moving rats for 3 hours after FMT injection (25 mg/kg, iv). Microdialy
sate collected 20 to 120 min post-dose, contained FMT at a concentrati
on (0.2 to 0.3 nM) approximately ten-fold below that of its metabolite
[F-18]fluoro-3-hydroxyphenylacetic acid (FPAC; 3.2 to 3.3 nM). D-amph
etamine (2.5 mg/kg, i.p.) injected 120 min after significantly increas
ed microdialysate FPAC (3.27 +/- 0.31 nM to 4.51 +/- 0.45 nM) in contr
ol but not reserpinized rats. Taken together these data demonstrate FM
T is heavily metabolized following its entry into the striatum yieldin
g FPAC which appears to be stored, at least in part, in reserpine sens
itive cytoplasmic vesicles. Presynaptic retention of FPAC may contribu
te to the preferential accumulation of FMT positron emission tomograph
y (PET) signaling in dopaminergic brain areas.