An in vivo microdialysis study of striatal 6-[18F]fluoro-L-m-tyrosine metabolism.
In vivo brain microdialysis was used to monitor 6-[18F]fluoro-L-m-tyrosine (FMT) uptake and metabolism in the striatum of conscious freely moving rats for 3 hours after FMT injection (25 mg/kg, i.v.). Microdialysate collected 20 to 120 min post-dose, contained FMT at a concentration (0.2 to 0.3 nM) approximately ten-fold below that of its metabolite [18F]fluoro-3-hydroxyphenylacetic acid (FPAC; 3.2 to 3.3 nM). D-amphetamine (2.5 mg/kg, i.p.) injected 120 min after significantly increased microdialysate FPAC (3.27 +/- 0.31 nM to 4.51 +/- 0.45 nM) in control but not reserpinized rats. Taken together these data demonstrate FMT is heavily metabolized following its entry into the striatum yielding FPAC which appears to be stored, at least in part, in reserpine sensitive cytoplasmic vesicles. Presynaptic retention of FPAC may contribute to the preferential accumulation of FMT positron emission tomography (PET) signaling in dopaminergic brain areas.
Jordan
S
S
Center for Functional Imaging, Lawrence Berkeley Laboratory, University of California, Berkeley 94720, USA. jorda02@aa.wl.com
Bankiewicz
K S
KS
Eberling
J L
JL
VanBrocklin
H F
HF
O'Neil
J P
JP
Jagust
W J
WJ
D000818:Animals; D001692:Biological Transport; D001711:Biotransformation; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D007700:Kinetics; D008297:Male; D017551:Microdialysis / Q000379:methods; D010648:Phenylacetates / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D005462:Fluorine Radioisotopes; D010648:Phenylacetates; C107830:3-fluoro-alpha-fluoromethyltyrosine; D014443:Tyrosine; C112330:3-fluoro-4-hydroxyphenylacetic acid; D012110:Reserpine; D003913:Dextroamphetamine