Kinetic compartment modeling of [11C]-5-hydroxy-L-tryptophan for positron emission tomography assessment of serotonin synthesis in human brain

The substrate for the second enzymatic step in serotonin synthesis, 5-hydroxy-L-tryptophan, labeled in the beta-position ([11C]-HTP), was used for positron emission tomography (PET) measurements in six healthy human participants, examined on two occasions. One- and two-tissue kinetic compartment modeling of time-radioactivity curves was performed, using arterial, metabolite-corrected [11C]-HTP values as input function. The availability of unchanged tracer in arterial blood plasma was > or = 80% up to 60 minutes after injection, while [11C]-hydroxyindole acetic acid and [11C]-serotonin accounted for the remaining radioactivity, amounting to < or = 16% and < or = 4%, respectively. Compartment modeling was performed for brain stem, putamen, caudate nucleus, anterior cingulate, white matter, and superior occipital, occipitotemporal, and temporal cortices. The average biologic half-life for plasma-to-tissue equilibrium was 7 to 12 minutes, and the volume of distribution was 0.2 to 0.5 microL.mL(-1). In all regions except white matter, the kinetic compartment model that included irreversible [11C]-HTP trapping showed significantly improved model fits with respect to a one-tissue compartment model. The [11C]-HTP trapping rate constant depended on the estimated tissue availability of the serotonin precursor tryptophan, known to reflect serotonin synthesis in healthy individuals, and correlated with serotonin tissue concentration and synthesis rates reported previously in literature. These findings suggest the use of [11C]-HTP PET measurements to investigate serotonin synthesis