Kinetic Analysis of Central [11C]Raclopride Binding to D2-Dopamine Receptors Studied by PET—A Comparison to the Equilibrium Analysis
Abstract
[11C]Raclopride binding to central D2-dopamine receptors in humans has previously been examined by positron emission tomography (PET). Based on the rapid occurrence of binding equilibrium, a saturation analysis has been developed for the determination of receptor density (Bmax) and affinity (Kd). For analysis of PET measurements obtained with other ligands, a kinetic three-compartment model has been used. In the present study, the brain uptake of [11C]raclopride was analyzed further by applying both a kinetic and an equilibrium analysis to data obtained from four PET experiments in each of three healthy subjects. First regional CBV was determined. In the second and third experiment, [11C]-raclopride with high and low specific activity was used. In a fourth experiment, the [11C]raclopride enantiomer [11C]FLB472 was used to examine the concentration of free radioligand and nonspecific binding in brain. Radio-activity in arterial blood was measured using an automated blood sampling system. Bmax and Kd values for [11C]raclopride binding could be determined also with the kinetic analysis. As expected theoretically, those values were similar to those obtained with the equilibrium analysis. In addition, the kinetic analysis allowed separate determination of the association and dissociation rate constants, kon and koff, respectively. Examination of [11C]raclopride and [11C]FLB472 uptake in brain regions devoid of specific D2-dopamine receptor binding indicated a fourth compartment in which uptake was reversible, nonstereoselective, and nonsaturable in the dose range studied.
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Article first published: October 1989
Issue published: October 1989
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Manuscript received: December 22, 1988
Revision received: April 17, 1989
Manuscript accepted: April 20, 1989
Published online: October 1, 1989
Issue published: October 1989
PubMed: 2528555
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