5-Hydroxy-l-[β-11C]tryptophan versus α-[11C]Methyl-l-tryptophan for Positron Emission Tomography Imaging of Serotonin Synthesis Capacity in the Rhesus Monkey Brain

• Published in: Journal of cerebral blood flow and metabolism Vol. 27; no. 4; pp. 821 - 830
• Main Authors: Lundquist, Pinelopi, Hartvig, Per, Blomquist, Gunnar, Hammarlund-Udenaes, Margareta, Långström, Bengt
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.04.2007; Lippincott Williams & Wilkins
• Subjects: 5-Hydroxy-L-tryptophan; 5-Hydroxytryptophan - pharmacokinetics; Animals; Biological and medical sciences; Biosynthesis; Body Weight - physiology; Brain Chemistry - physiology; Dose-Response Relationship, Drug; FARMACI; Female; Fundamental and applied biological sciences. Psychology; Investigative techniques, diagnostic techniques (general aspects); Macaca mulatta; Medical sciences; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Nervous system; Neurology; PHARMACY; Positron emission tomography; Radionuclide investigations; Radiopharmaceuticals - pharmacokinetics; Rhesus monkey; Serotonin; Serotonin - biosynthesis; Tryptophan - analogs & derivatives; Tryptophan - pharmacokinetics; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; α-Methyl-L-tryptophan; rhesus monkey; serotonin; α-Methyl-l-tryptophan; 5-Hydroxy-l-tryptophan; positron emission tomography; biosynthesis; Nervous system diseases; Serotonin; Monkey; Tryptophan; Biosynthesis; Cerebral disorder; α-Methyl-L-tryptophan; Vertebrata; Mammalia; Aminoacid; Animal; Central nervous system disease; Neurotransmitter; Primates; 5-Hydroxy-L-tryptophan; Positron emission tomography; Cerebrovascular disease; Comparative study; Emission tomography
• ISSN: 0271-678X; 1559-7016; 1559-7016
• DOI: 10.1038/sj.jcbfm.9600381

The purpose of this study was to compare two positron emission tomography (PET) tracers that were developed to follow serotonin (5HT) synthesis by performing sequential PET scanning of the same rhesus monkey (n = 4) on the same day. α-[11C]Methyl-l-tryptophan ([11C]AMT) and 5-Hydroxy-l-[β-11C]tryptophan ([11C]HTP) are substrates in the first and second enzymatic steps, respectively, in the biosynthesis of 5HT. Regional net accumulation rate constants were derived from kinetic (two-tissue compartment model with irreversible tracer trapping) and graphic (Patlak) analyses, using the arterial plasma concentrations as input. The kinetic data analysis showed that the rate constant for the transfer of [11C]HTP into the brain (K1) was higher than that for [11C]AMT in the striatum and thalamus but was similar in other brain regions. The rate constant for tracer trapping (k3) was also higher for [11C]HTP than for [11C]AMT in the striatum (0.046 ± 0.024 versus 0.019 ± 0.006 min−1) and thalamus (0.039 ± 0.013 versus 0.016 ± 0.007 min−1). In agreement with previously reported regional HTP accumulation rates, the net accumulation rate constant (Kacc) for [11C]HTP was also higher in these regions than in other brain regions; this is in contrast to the uniform distribution of [11C]AMT Kacc values. This suggests that the regional net accumulation rates obtained with these two PET tracers will be of different magnitude, which might be related to the activity of each targeted enzyme.