The Suitability of [ C]-α-Methyl-L-tryptophan as a Tracer for Serotonin Synthesis: Studies With Dual Administration of [ C] and [ C] Labeled Tracer

• Published in: Journal of cerebral blood flow and metabolism Vol. 20; no. 2; pp. 244 - 252
• Main Authors: Shoaf, Susan E., Carson, Richard E., Hommer, Daniel, Williams, Wendol A., Higley, J. Dee, Schmall, Bernard, Herscovitch, Peter, Eckelman, William C., Linnoila, Markku
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-02-2000; Lippincott Williams & Wilkins
• Subjects: Animals; Biological and medical sciences; Brain - diagnostic imaging; Brain - metabolism; Brain Chemistry; Carbon Radioisotopes; Cerebrovascular Circulation; Hydroxyindoleacetic Acid - analysis; Hydroxyindoleacetic Acid - metabolism; Investigative techniques, diagnostic techniques (general aspects); Macaca mulatta; Male; Medical sciences; Osteoarticular system. Muscles; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Serotonin - analysis; Serotonin - biosynthesis; Serotonin - metabolism; Tomography, Emission-Computed - methods; Tryptophan - analogs & derivatives; Tryptophan - analysis; Tryptophan - blood; Tryptophan - pharmacokinetics; Brain; Serotonin; Pharmacokinetics; Positron emission tomography; Rhesus monkeys; α-Methyl-L-tryptophan; Radionuclide study; Radiolabelling; Central nervous system; Monkey; Radioisotope; Metabolism; Vertebrata; Mammalia; Protein synthesis; Animal; Primates; Kinetics; Technique; Brain (vertebrata); Positron; Emission tomography
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1097/00004647-200002000-00004

The tracer [11C]-α-methyl-L-tryptophan (αMTP) has been used to measure brain serotonin synthesis rates with positron emission tomography (PET). To address questions about the accuracy of the kinetic model, [14C]αMTP was used to directly measure conversion to [14C]-α-methyl-serotonin (αM5HT) in monkeys that had been previously studied with PET and [11C]αMTP. Four male, fasted, isoflurane-anesthetized rhesus monkeys were studied with [11C]αMTP and PET. Immediately after the initial 3-hour scan, a second dose of [11C]αMTP was coinjected with 1 mCi of [14C]αMTP, and additional PET data were collected. Approximately 90 minutes after the second αMTP 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 αMTP to αM5HT occurred; HPLC analysis of 14C radioactivity showed that greater than 96% of the total counts were in fractions corresponding to the αMTP peak. Brain concentrations of serotonin, tryptophan, 5-hydroxyindole-3-acetic acid, and αMTP also were determined fluorometrically using external 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 [14C]αM5HT. These data indicate that in the 3-hour period after injection, [11C]αMTP is acting predominantly as a tracer of tryptophan uptake, not serotonin synthesis.