Accuracy of in vivo neuroreceptor quantification by PET and review of steady-state, transient, double injection, and equilibrium models

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Abstract
The accuracy of in vivo dopamine D2 receptor quantification by positron emission tomography (PET) was determined for several models by means of singular-value decomposition, and some of the model assumptions were reviewed. These include steady-state, transient, double injection, and equilibrium approaches. All four modes are augmented by including a realistic kinetic interaction of the radioligand with the striatal serotonin S2 receptor. When a set of parameters derived specifically with reference to the equilibrium model was applied, it was found that a reversible radioligand used in conjunction with the equilibrium model permits accurate quantification. However, an assumption of the equilibrium model-that equilibrium is achieved during the time of measurement-is shown to be unsupported by the published experimental data. These results indicate that the equilibrium approach can provide an alternative to the kinetic approaches, but that additional experimental evidence is required to demonstrate the validity of the equilibrium assumption.