Alpha[C-11]methyl-L-tryptophan PET maps brain serotonin synthesis and kynurenine pathway metabolism

Abstract

Alpha[C-11]methyl-L-tryptophan (AMT) is an analog of tryptophan used with positron emission tomography for the measurement of serotonin synthesis in humans. Several attempts have been made to estimate the serotonin synthesis rate from plasma and brain kinetic data of AMT using the same model as that applied for the measurement of the glucose metabolic rate with 2-deoxyglucose. However, although AMT is similar to 2-deoxyglucose with regard to an irreversible pool of tracer uptake, there are important differences between the two tracers and how the model can be applied. These differences include transport at the blood-brain barrier and the presence of a large unmetabolized pool of AMT, precluding the method from providing the absolute serotonin synthesis rate. Despite this limitation, the unidirectional uptake rate constant (K-complex) values have been found to be stable within an individual, and the rank order of regional brain values for K-complex are consistent with the rank order for serotonin content in human brain. Furthermore, changes in K-complex with age, gender, and disease states are consistent with previously reported biochemical measurements of serotonin in brain tissue. The authors suggest, therefore, that the K-complex is an index of serotonin synthesis which they have termed the "serotonin synthesis capacity." The authors argue that AMT is a useful tracer for study of serotonergic mechanisms, and under certain pathologic states, of metabolism by means of the kynurenine pathway.