Summary:The substrate for the second enzymatic step in serotonin synthesis, 5-hydroxy-L-tryptophan, labeled in the -position ([ 11 C]-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 [11 C]-HTP values as input function. The availability of unchanged tracer in arterial blood plasma was Ն 80% up to 60 minutes after injection, while [ 11 C]-hydroxyindole acetic acid and [ 11 C]-serotonin accounted for the remaining radioactivity, amounting to Յ16% and Յ4%, 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 L·mL