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

P Cumming, G C Léger, H Kuwabara, A Gjedde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 1993-Jul
OriginalsprogEngelsk
TidsskriftJournal of Cerebral Blood Flow and Metabolism
Vol/bind13
Udgave nummer4
Sider (fra-til)668-75
Antal sider7
ISSN0271-678X
StatusUdgivet - 1993
Udgivet eksterntJa

Fingeraftryk

Pharmacokinetics
Decarboxylation
High Pressure Liquid Chromatography
Population
Electrons
Enzymes

Citer dette

@article{022b14ebed7d4f4e9866a70837fa4876,
title = "Pharmacokinetics of plasma 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]Fdopa) in humans.",
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.",
author = "P Cumming and L{\'e}ger, {G C} and H Kuwabara and A Gjedde",
year = "1993",
language = "English",
volume = "13",
pages = "668--75",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "SAGE Publications",
number = "4",

}

Pharmacokinetics of plasma 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]Fdopa) in humans. / Cumming, P; Léger, G C; Kuwabara, H; Gjedde, A.

I: Journal of Cerebral Blood Flow and Metabolism, Bind 13, Nr. 4, 1993, s. 668-75.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Pharmacokinetics of plasma 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]Fdopa) in humans.

AU - Cumming, P

AU - Léger, G C

AU - Kuwabara, H

AU - Gjedde, A

PY - 1993

Y1 - 1993

N2 - 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.

AB - 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.

M3 - Journal article

VL - 13

SP - 668

EP - 675

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 4

ER -