An in vivo microdialysis study of striatal 6-[18F]fluoro-L-m-tyrosine metabolism

被引:11
作者
Jordan, S
Bankiewicz, KS
Eberling, JL
Vanbrocklin, HF
O'Neil, JP
Jagust, WJ
机构
[1] Univ Calif Berkeley, Lawrence Berkeley Lab, Ctr Funct Imaging, Berkeley, CA 94720 USA
[2] Somatix Therapy Corp, Alameda, CA 94501 USA
[3] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA
关键词
amphetamine; 6-[F-18]fluoro-L-m-tyrosine; metabolism; microdialysis; PET; striatum;
D O I
10.1023/A:1022478417383
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In vivo brain microdialysis was used to monitor 6-[F-18]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, iv). 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 [F-18]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.
引用
收藏
页码:513 / 517
页数:5
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