BLOOD-BRAIN TRANSFER AND METABOLISM OF 6-[F-18]FLUORO-L-DOPA IN RAT

被引:52
|
作者
REITH, J
DYVE, S
KUWABARA, H
GUTTMAN, M
DIKSIC, M
GJEDDE, A
机构
[1] MCGILL UNIV,MONTREAL NEUROL INST,MCCONNELL BRAIN IMAGING CTR,MONTREAL H3A 2B4,QUEBEC,CANADA
[2] MCGILL UNIV,DEPT NEUROL & NEUROSURG,MONTREAL H3A 2B4,QUEBEC,CANADA
来源
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 1990年 / 10卷 / 05期
关键词
Amino acids; Blood-brain barrier; Catechol-O-methyltransferase; DOPA decarboxylase; Dopamine; Fluoro-3,4-dihydroxyphenylalanine; Positron emission tomography; Striatum;
D O I
10.1038/jcbfm.1990.124
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In a study designed to reveal the rates of blood-brain transfer and decarboxylation of fluoro-L-3,4-dihydroxyphenylalanine (FDOPA), we discovered a major discrepancy between the DOPA decarboxylase activity reported in the literature and the rate of FDOPA decarboxylation measured in the study. "Donor" rats received intravenous injections of 6 mCi fluorine-18-labeled FDOPA. The donor rats synthesized methyl-FDOPA. Arterial plasma, containing both FDOPA and methyl-FDOPA, was sampled from the donor rats at different times and reinjected into "recipient" rats in which it circulated for 20 s. The blood-brain clearance of the mixture of labeled tracers in the plasma was determined by an integral method. The individual permeabilities were determined by linear regression analysis, according to witch the average methyl-FDOPA permeability in the blood-brain barrier was twice that of FDOPA, which av-eraged 0.037 ml g-1 min-1. The permeability ratio was used to determine the fractional clearance from the brain of FDOPA (and hence of methyl-FDOPA), which averaged 0.081 min-1. In the striatum, the measured average FDOPA decarboxylation rate constant (k3D) was 0.010 min-1, or no more than 1% of the rate of striatal decarboxylation of DOPA measured in vitro and in vivo. We interpreted this finding as further evidence in favor of the hypothesis that striatum has two dopamine (DA) pools, of which only DA in the large pool is protected from metabolism. Hence, no more than 1% of the quantity of fluoro-DA theoretically synthesized was actually retained in striatum.
引用
收藏
页码:707 / 719
页数:13
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