A two-compartment description and kinetic procedure for measuring regional cerebral ( sup 11 C)nomifensine uptake using positron emission tomography

Journal Article · Tue May 01 04:00:00 EDT 1990 · Journal of Cerebral Blood Flow and Metabolism; (USA)

DOI:https://doi.org/10.1038/jcbfm.1990.59· OSTI ID:7044920

Salmon, E; Brooks, D J; Leenders, K L; Turton, D R; Hume, S P; Cremer, J E; Jones, T; Frackowiak, R S ^[1]

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1. Hammersmith Hospital, London (England)

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.

• OSTI ID: 7044920
• Journal Information: Journal of Cerebral Blood Flow and Metabolism; (USA), Journal Name: Journal of Cerebral Blood Flow and Metabolism; (USA) Vol. 10:3; ISSN 0271-678X; ISSN JCBMD
• Country of Publication: United States
• Language: English

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550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
BRAIN
CARBON 11
CARBON ISOTOPES
CENTRAL NERVOUS SYSTEM
CEREBELLUM
CEREBRAL CORTEX
CEREBRUM
COMPUTERIZED TOMOGRAPHY
DIAGNOSIS
DIAGNOSTIC TECHNIQUES
DISEASES
DISTRIBUTION
DRUGS
EMISSION COMPUTED TOMOGRAPHY
EVEN-ODD NUCLEI
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
NUCLEI
ORGANS
POSITRON COMPUTED TOMOGRAPHY
RADIOISOTOPES
RADIOPHARMACEUTICALS
THALAMUS
TISSUE DISTRIBUTION
TOMOGRAPHY