Quantification of baboon cortical S2 serotonin receptors in vivo with 3-N-(2'-F18)fluoroethylspiperone and positron emission tomography.

We used the ligand 3-N-(2'-F18)fluoroethylspiperone (FESP) and positron emission tomography (PET) to quantify in vivo serotonin S2 neuroreceptor density and affinity in the baboon frontal cortex. In the cortex, FESP binds specifically and exclusively to S2 receptors, and an equilibrium is reached when the rate of ligand-receptor association and dissociation become equal. Using multiple studies in the same baboon, an equilibrium (saturation) analysis approach provided a linear Hill plot with a slope of 1.02 (r2 = 0.988, P less than 0.0001), indicative of ligand binding to a single receptor class. Using serial PET scans, a dynamic approach was also used to quantify S2 receptors in the frontal cortex of the baboon, which provided an estimate of receptor density Bmax = 35.6 +/- 10.9 pmol/g. The rate constants corresponding to transport into and out of tissue were K1* = 0.2720 +/- 0.0299 mol/min.g and k2* = 0.0786 +/- 0.0315 min-1, respectively. The ligand-receptor dissociation constant was k4* = 0.0154 +/- 0.0109 min-1.