Pharmacokinetics of plasma 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA) in humans

Paul Cumming, Gabriel C. Léger, Hiroto Kuwabara, Albert Gjedde

Research output: Contribution to journalArticle

Abstract

Like native DOPA, [18F]-6-fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA) is subject to methylation and decarboxylation. To determine the rates of formation and elimination of [18F]FDOPA metabolites, plasma from human subjects undergoing positron emission tomographic (PET) studies was analyzed by high-performance liquid chromatography (HPLC). In addition to the principal metabolite O-methyl-[18F]FDOPA (OMe-[18F]FDOPA), two decarboxylated metabolites were detected in plasma from carbidopa pretreated subjects. The concentrations of each metabolite during 90 min following tracer injection could be described as a function of the concentration of [18F]FDOPA, and two rate constants; k0, the rate of formation, and k-1, the rate of clearance. Plasma metabolite time series generated from total plasma activity curves and measured rate constants were in close agreement with the actual concentrations determined by HPLC fractionation. Population means for k0 (0.011 ± 0.002 min-1) and K-1 (0.010 ± 0.003 min-1) were used to generate "simulated" plasma curves. The measured and generated plasma curves were used as inputs for estimation of partition and decarboxylation coefficients of [18F]FDOPA in brain. The use of generated input functions from normal population means of transfer coefficients did not introduce a systematic error into the estimate of the enzyme activity. However, the high variability of these estimates in patients precludes the use of this technique as an alterative to individual HPLC measurements.

Original languageEnglish (US)
Pages (from-to)668-675
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume13
Issue number4
DOIs
StatePublished - Jan 1 1993

Keywords

  • 6-[F]Fluoro-L-DOPA
  • Metabolism
  • Modeling
  • O-Methyl-6-[F]Fluoro-L-DOPA
  • Positron emission tomography

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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