A two-compartment description and kinetic procedure for measuring regional cerebral [11C]nomifensine uptake using positron emission tomography.

Détails

ID Serval
serval:BIB_917A8D27F2A4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A two-compartment description and kinetic procedure for measuring regional cerebral [11C]nomifensine uptake using positron emission tomography.
Périodique
Journal of Cerebral Blood Flow and Metabolism
Auteur⸱e⸱s
Salmon E., Brooks D.J., Leenders K.L., Turton D.R., Hume S.P., Cremer J.E., Jones T., Frackowiak R.S.
ISSN
0271-678X (Print)
ISSN-L
0271-678X
Statut éditorial
Publié
Date de publication
1990
Volume
10
Numéro
3
Pages
307-316
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
S-[11C]Nomifensine (S-[11C]NMF) is a positron-emitting tracer suitable for positron emission tomography, which binds to both dopaminergic and noradrenergic reuptake sites in the striatum and the thalamus. Modelling of the cerebral distribution of this drug has been hampered by the rapid appearance of glucuronide metabolites in the plasma, which do not cross the blood--brain barrier. To date, [11C]NMF uptake has simply been expressed as regional versus nonspecific cerebellar activity ratios. We have calculated a "free" NMF input curve from red cell activity curves, using the fact that the free drug rapidly equilibrates between red cells and plasma, while glucuronides do not enter red cells. With this free [11C]NMF input function, all regional cerebral uptake curves could be fitted to a conventional two-compartment model, defining tracer distribution in terms of [11C]NMF regional volume of distribution. Assuming that the cerebellar volume of distribution of [11C]NMF represents the nonspecific volume of distribution of the tracer in striatum and thalamus, we have calculated an equilibrium partition coefficient for [11C]NMF between freely exchanging specific and nonspecific compartments in these regions, representing its "binding potential" to dopaminergic or noradrenergic uptake sites (or complexes). This partition coefficient was lower in the striatum when the racemate rather than the active S-enantiomer of [11C]NMF was administered. In the striatum of patients suffering from Parkinson's disease and multiple-system atrophy, the specific compartmentation of S-[11C]NMF was significantly decreased compared with that of age-matched volunteers.
Mots-clé
Brain/metabolism, Carbon Radioisotopes/diagnostic use, Caudate Nucleus/metabolism, Cerebellum/metabolism, Cerebral Cortex/metabolism, Humans, Models, Theoretical, Nomifensine/blood, Nomifensine/pharmacokinetics, Parkinson Disease/metabolism, Putamen/metabolism, Shy-Drager Syndrome/metabolism, Thalamus/metabolism, Tissue Distribution, Tomography, Emission-Computed
Pubmed
Web of science
Création de la notice
08/10/2011 13:42
Dernière modification de la notice
20/08/2019 14:54
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