Positron emission tomography quantification of [11C]-(+)-PHNO binding in the human brain.
J Cereb Blood Flow Metab
; 27(4): 857-71, 2007 Apr.
Article
em En
| MEDLINE
| ID: mdl-17033687
ABSTRACT
The kinetic modeling of [11C]-(+)-PHNO binding to the dopamine D2/3 receptors in six human volunteers using positron emission tomography (PET) is described. [11C]-(+)-PHNO is the first agonist radioligand for the D2/3 in humans and as expected showed high uptake in caudate, putamen, globus pallidus (GP) and ventral striatum, and low uptake in cerebellum. A two-tissue compartment model (2CM) with four parameters was necessary to adequately fit time-activity data in all regions. Although a 2CM provided an excellent estimation of total distribution volumes, which were highly correlated with those obtained with the invasive Logan approach, it provided a poor identification of the k3/k4 ratios. Coupling K1/k2 between brain regions (Method C) or fixing K1/k2 to the value obtained in cerebellum (Method D) enabled more stable estimates of k3/k4 as compared with an unconstrained 2CM. The k3/k4 obtained with Method D ranged from 0.12+/-0.03 in cerebellum to 3.93+/-0.77 in GP and were similar to those obtained when coupling K1/k2. Binding potentials (BPs) obtained using the simplified reference tissue model (BP(SRTM)) ranged from 2.08+/-0.34 in caudate to 3.55+/-0.78 in GP and were highly correlated with k3/k4 estimates obtained with Method D (r=0.98). However, BP(SRTM) were 11%+/-5% lower than values obtained with Method D. BPs derived using the noninvasive Logan approach were slightly lower but not significantly different than BP(SRTM). This study demonstrates that [11C]-(+)-PHNO can be used for the quantitative measurement of D2/3 densities and should enable further studies of potential D2/3 dysregulation in several important psychiatric and neurologic illnesses.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxazinas
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Encéfalo
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Compostos Radiofarmacêuticos
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Cereb Blood Flow Metab
Ano de publicação:
2007
Tipo de documento:
Article