Fig. 3.

Metabolism of [¹¹C]5-HTP. Most of 5-HT synthesis takes place in the terminal areas. Tryptophan is acquired through the diet and is transported across the blood-brain barrier (BBB) by the large amino acid transporter (LAT). Within neurons Trp is catabolized by tryptophan hydroxylase (TPH) to 5-HTP. Subsequently, 5-HTP is converted to 5-HT by AADC. PCPA and NSD 1015 can block TPH and AADC, respectively. 5-HT is taken up and stored in vesicles by the vesicular monoamine transporter (VMAT). When neurons fire, the vesicles fuse with the synaptic membrane whereafter 5-HT is released within the synaptic cleft. The serotonin transporter (SERT) causes reuptake of 5-HT that can either be restored into vesicles or be broken down by monoamine oxidase (MAO) to 5-HIAA. Eventually, 5-HIAA is released into the bloodstream and excreted by the kidneys. A similar process takes place in peripheral organs. Radiolabelled 5-HTP undergoes the same conversions as endogenous 5-HTP and is therefore a suitable tracer for 5-HT synthesis. A two-tissue compartment model with irreversible tracer trapping can be used for modelling [¹¹C]5-HTP kinetics. The rate constant for transport from plasma to brain is indicated by K ₁, k ₂ represents efflux of the tracer back into the bloodstream and k ₃ is the irreversible trapping constant