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The in vivo tracer kinetics of 3-(2apos;-[ 18 F]fluoroethyl)spiperone (FESP) in the caudate/striatum and cerebellar regions of the human and monkey brain were studied with positron emission tomography (PET). The minimal model configuration that can describe the kinetics was determined statistically. Three two-compartment model configurations were found to be suitable for describing the kinetics in caudate/striatum and cerebellum: (1) a nonlinear model (five parameters) applicable to studies using nontracer (partially saturating) quantities of FESP in monkey striatum, (2) a linear four-parameter model applicable to the caudate/striatal and cerebellar kinetics in human and monkey studies with tracer quantities of FESP, and (3) a linear three-parameter model derived from the four-parameter model by assuming irreversible binding applicable to tracer studies of the human caudate. In the human studies, when the caudate kinetics ( n = 4) were fit by model 2 (with four parameters), the value of the in vivo ligand dissociation constant k d  was found to be 0.0015 ± 0.0032/min. The three-parameter model (model 3) was found to fit the data equally well; this model is equivalent to model 2 with k d  set to zero. In the monkey studies, it was found that for short (90 min) studies using tracer quantities of FESP, model 2 fit the striatal kinetics better than model 3. The parameters estimated using model 2 (four parameters) were in better agreement with those estimated by the nonlinear model (model 1) than those estimated using model 3 (three parameters). The use of a graphical approach gives estimates of the plasma–tissue fractional transport rate constant K 1  and the net uptake constant K 3  comparable to estimates using model 3 for both human and monkey studies.

journal of cerebral blood flow and metabolism

Models for in vivo Kinetic Interactions of Dopamine D2-Neuroreceptors and 3-(2'-[<sup>18</sup>F]Fluoroethyl)Spiperone Examined with Positron Emission Tomography

Models for in vivo Kinetic Interactions of Dopamine D2-Neuroreceptors and 3-(2'-[18F]Fluoroethyl)Spiperone Examined with Positron Emission Tomography

Models for in vivo Kinetic Interactions of Dopamine D2-Neuroreceptors and 3-(2'-[¹⁸F]Fluoroethyl)Spiperone Examined with Positron Emission Tomography