Quantification of baboon cortical S₂ serotonin receptors in vivo with 3-N-(2′-Fl8)fluoroethylspiperone and positron emission tomography

Abstract

We used the ligand 3-N-(2′-F 18)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 (r ² =0.988,P <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 densityB _max =35.6 ± 10.9 pmol/g. The rate constants corresponding to transport into and out of tissue wereK ¹_* = 0.2720 ± 0.0299 mol/min ⁗ g andk ²_* = 0.0786 ± 0.0315 min⁻¹, respectively. The ligand-receptor dissociation constant wask ⁴_* = 0.0154 ± 0.0109 min⁻¹.