The suitability of [11C]-α-methyl-L-tryptophan as a tracer for serotonin synthesis:: Studies with dual administration of [11C] and [14C] labeled tracer

The tracer [C-11]-alpha-methyl-L-tryptophan (alpha MTP) has been used to measure brain serotonin synthesis rates with positron emission tomography (PET). To address questions about the accuracy of the kinetic model, [C-14]alpha MTP was used to directly measure conversion to [C-14]-alpha-methyl-serotonin (alpha M5HT) in monkeys that had been previously studied with PET and [C-11]alpha MTP. Four male, fasted, isonurane-anesthetized rhesus monkeys were studied with [C-11]aMTP and PET. Immediately after the initial 3-hour scan, a second dose of [C-11]alpha MTP was coinjected with 1 mCi of [C-14]alpha MTP, and additional PET data were collected. Approximately 90 minutes after the second aMTP administration. the animals were killed with an overdose of phenobarbital. and brain samples from 21 regions were taken and analyzed by HPLC. Minimal conversion of alpha MTP to alpha M5HT occurred; HPLC analysis of C-14 radioactivity showed that greater than 96% of the total counts were in fractions corresponding to the alpha MTP peak. Brain concentrations of serotonin, tryptophan, 5-hydroxyindole-3-acetic acid, and alpha MTP also were determined fluorometrically using exernal quantification. Patlak plots generated from PET images acquired over 3 hours showed no time period of linear increase, and final slopes were not significantly different from zero, consistent With the finding of minimal conversion to [C-14]alpha M5HT. These data indicate that in the 3-hour period after injection, [C-11]alpha MTP is acting predominantly as a tracer of tryptophan uptake, not serotonin synthesis.