HUMAN BRAIN-SEROTONIN SYNTHESIS CAPACITY MEASURED IN-VIVO WITH ALPHA-[C-11]METHYL-L-TRYPTOPHAN

Local cerebral serotonin synthesis capacity was measured with alpha-[C -11]methyl-L-tryptophan ([C-11]AMT) in normal adult human brain (n = 1 0; five males, five females; age range, 18-38 years, mean 28.3 years) by using positron emission tomography (PET). [C-11]AMT is an analog of tryptophan, the precursor for serotonin synthesis, and is converted t o alpha-[C-11]methyl-serotonin ([C-11]AM-5HT), which is trapped in ser otonergic neurons because [C-11]AM-5HT is not degraded by monoamine ox idase. Kinetic analysis of [C-ll] activity in brain after injection of [C-11]AMT confirmed the presence of a compartment with unidirectional uptake that represented approximately 40% of the activity in the brai n at 50 min after tracer administration. The undirectional rate consta nt K, which represents the uptake of [C-11]AMT from the plasma to brai n tissue followed by the synthesis and physiologic trapping of [C-11]A M-5HT, was calculated using the Patlak graphic approach on a pixel-by- pixel basis, thus creating parametric images. The rank order of K valu es for different brain regions corresponded well to the regional conce ntrations of serotonin in human brain (P <.0001). High serotonin synth esis capacity values were measured in putamen, caudate, thalamus, and hippocampus. Among cortical regions, the highest values were measured in the rectal gyrus of the inferior frontal lobe, followed by transver se temporal gyrus; anterior and posterior cingulate gyrus; middle, sup erior, and inferior temporal gyri; parietal cortex; occipital cortex, in descending order. Values in women were 10-20% higher (P <.05, MANOV A) throughout the brain than those measured in men. Differences in the serotonin synthesis capacity between men and women measured in this s tudy may reflect gender differences of importance to both normal and p athologic behavior. This study demonstrates the suitability of [C-11]A MT as a tracer for PET scanning of serotonin synthesis capacity in hum an brain and provides normal adult values for future comparison with p atient groups. (C) 1998 Wiley-Liss, Inc.