Human brain serotonin synthesis capacity measured in vivo with ?-[C-11]methyl-L-tryptophan

Abstract

Local cerebral serotonin synthesis capacity was measured with alpha-[C-11]methyl-L-tryptophan ([C-11]AMT) in normal adult human brain (n = 10; 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 to alpha-[C-11]methyl-serotonin ([C-11]AM-5HT), which is trapped in serotonergic neurons because [C-11]AM-5HT is not degraded by monoamine oxidase. Kinetic analysis of [C-11] 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 brain at 50 min after tracer administration. The undirectional rate constant K, which represents the uptake of [C-11]AMT from the plasma to brain tissue followed by the synthesis and physiologic trapping of [C-11]AM-5HT, was calculated using the Patlak graphic approach on a pixel-by-pixel basis, thus creating parametric images. The rank order of K values for different brain regions corresponded well to the regional concentrations of serotonin in human brain (P < .0001). High serotonin synthesis 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 transverse temporal gyrus; anterior and posterior cingulate gyrus; middle, superior, and inferior temporal gyri; parietal cortex; occipital cortex, in descending order. Values in women were 10-20% higher (P < .05, MANOVA) throughout the brain than those measured in men. Differences in the serotonin synthesis capacity between men and women measured in this study may reflect gender differences of importance to both normal and pathologic behavior. This study demonstrates the suitability of [C-11]AMT as a tracer for PET scanning of serotonin synthesis capacity in human brain and provides normal adult values for future comparison with patient groups.

Study of the brain serotonergic system with labeled α‐methyl‐l‐tryptophan

“…In this study, females were found to have a lower mean rate of 5‐HT synthesis, an effect caused by lower free‐plasma Trp rather than a lower value of K . This contrasts with the results of Chugani et al . (1998c), who reported that K was on average 15% higher in women, but did not report on free‐plasma Trp or on the rate of 5‐HT synthesis.…”

Postnatal maturation of human GABAA receptors measured with positron emission tomography

“…In the present study, all brain regions studied showed the highest value for FMZ VD at two years of age, which was the youngest age measured, and the FMZ VD values subsequently decreased exponentially with age. Gender differences, which showed approximately 10% higher FMZ VD in women than in men, are consistent with similar gender differences previously reported for glucose metabolism,48 cerebral blood flow,49 and serotonin synthesis capacity 50. During development, medial temporal lobe structures, primary visual cortex, and thalamus showed larger differences between two years of age (α) and adult (C adult; approximately 50% decrease) than did basal ganglia, cerebellum, and other cortical regions (25–40%).…”

Quantification of Tryptophan Transport and Metabolism in Lung Tumors Using PET

“…Moreover, both these values were higher than previously determined in normal brain tissue (0.014 ± 0.003, [25]), consistent with a lack of a blood-tissue barrier, such as the blood-brain barrier in the brain. In one patient (patient #5) visual inspection of lung tissue time-activity curves suggested possible metabolic retention of AMT, thus we applied both a two- and three-compartment model to this patient's lung tissue curve.…”