C-11 alpha-methyl-L-tryptophan (AMT) is being used to assess the turnover of serotonin, a major transmitter in the brain that is linked to depression and impulsive behavior. Studies are being conducted with the tracer in monkeys before its use in humans. The monkeys being studied have high or low levels of aggressive behavior, and it is hoped that they will show differences in AMT uptake. A chiral precursor to [C-11]AMT is commercially available. Several procedures have been reported utilizing this material for the synthesis of [C-11]AMT. Although the methylation reaction using [C11]methyl iodide are similar in these procedures, the hydrolysis steps leading to [C-11]AMT are different. In our attempts to synthesize [C-11]AMT, we did not obtain reproducible results by the method of hydrolysis using hydrogen iodide. More consistent results were obtained by the method of hydrolysis using trifluoroacetic acid/ION sodium hydroxide. We obtained [C-11]AMT with a radiopurity greater than 99 percent and a radiochemical yield of about 40 percent. No D-isomer could be detected. [C-11]AM4T (1.5 to 5 mCi) was injected in three monkeys to determine the brain uptake and absorbed radiation dose. Whole-body scans were obtained using the General Electric Advance. The average residence times for lung, liver, kidney, brain, and heart were 0.67, 1.44, 1.52, 0.22, and 0.21, respectively. The kidney is the critical organ at 0.022 mGy/mBy (0.083 rad/mCi). Time-activity curves in monkey brain were determined for cortical gray matter, subcortical gray matter, and white matter.
