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A Kinetic Analysis of 6‐[ 18 F]Fluoro‐ l ‐Dihydroxyphenylalanine Metabolism in the Rat
Author(s) -
Cumming Paul,
Kuwabara Hiroto,
Gjedde Albert
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.63051675.x
Subject(s) - chemistry , striatum , reaction rate constant , elimination rate constant , carbidopa , decarboxylation , distribution volume , dihydroxyphenylalanine , metabolism , metabolite , volume of distribution , monoamine oxidase , dopamine , kinetics , biochemistry , endocrinology , medicine , pharmacokinetics , levodopa , enzyme , biology , physics , disease , quantum mechanics , parkinson's disease , catalysis
A previous study of the metabolism of 6‐[ 18 F]‐fluoro‐ l ‐3,4‐dihydroxyphenylalanine (FDOPA) in rats pretreated with carbidopa contained information amenable to kinetic analysis. Using these data, tracer transfer coefficients and metabolic rate constants were estimated. After intravenous injection, FDOPA in circulation was O ‐methylated ( k D 0 = 0.055 min −1 ), and the metabolite ( O ‐methyl‐FDOPA) escaped from plasma with a rate constant ( k M −1 ) of 0.01 min −1 . The initial clearance of FDOPA to striatum ( K D 1 ) was 0.07 ml g −1 min −1 , and the equilibrium distribution volume ( V D e ) was 0.67 ml g −1 . The initial clearance of O ‐methyl‐FDOPA to striatum ( K M 1 ) was 0.08 ml g −1 min −1 , and the equilibrium distribution volume ( V M e ) was 0.75 ml g −1 . The rate constant of FDOPA decarboxylation ( k D 3 ) was 0.17 min −1 in striatum. The elimination of 6‐[ 18 F]fluorodopamine (FDA) from striatum suggested an apparent rate constant for monoamine oxidase activity ( k ′ 7 ) of 0.055 min −1 . 6‐[ 18 F]Fluorohomovanillic acid (FHVA) was formed from 6‐[ 18 F]fluoro‐ l ‐3,4‐dihydroxyphenylacetic acid with a rate constant ( k 11 ) of 0.083 min −1 , and FHVA was eliminated from striatum ( k 9 ) with a rate constant of 0.12 min −1 . The steady‐state concentration ratios of FDA and its metabolites were shown to be functions of these rate constants.