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

Abstract

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. a-[ 11 C]Methyl-L-tryptophan ([ 11 C]AMT) and 5-Hydroxy-L-[b-11 C]tryptophan ([ 11 C]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 [ 11 C]HTP into the brain (K 1) was higher than that for [ 11 C]AMT in the striatum and thalamus but was similar in other brain regions. The rate constant for tracer trapping (k 3) was also higher for [ 11 C]HTP than for [ 11 C]AMT in the striatum (0.04660.024 versus 0.01960.006 min À1) and thalamus (0.03960.013 versus 0.01660.007 min À1). In agreement with previously reported regional HTP accumulation rates, the net accumulation rate constant (K acc) for [ 11 C]HTP was also higher in these regions than in other brain regions; this is in contrast to the uniform distribution of [ 11 C]AMT K acc 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.

Brain Serotonin Synthesis in Adult Males Characterized by Physical Aggression during Childhood: A 21-Year Longitudinal Study

“…Experimental evidence accumulated over more than 10 years [23], [42], [43], [44], [45], [46] now provides a firm basis for a consensus that brain regional 11 C-AMT trapping represents an acceptable index of 5-HT synthesis. Of particular interest is the report of Patlak plots of 11 C-AMT brain uptake estimated in primates, with a slope significantly different from zero, and providing unequivocal evidence for brain trapping of the tracer [24]. (2) The study was conducted between 2002 and 2007.…”

“…The advantages and disadvantages of the method have been described previously [45]. Overall, a general consensus is emerging that brain regional 11 C-AMT trapping provides an acceptable proxy for 5-HT synthesis [23], [24], [45], [55]. All images were collected and reconstructed using a 3-dimensional mode with an intrinsic resolution of 5×5×5 mm full width at half maximum, with 26 frames, each with 128×128 voxels and 63 slices and a voxel size of 2.4×2×2 mm.…”

“…Genotyping for the rate-limiting 5-HT synthesis enzyme, tryptophan-hydroxylase2 ( TPH 2 ) and prospective measures of early and late life adversity were also collected in order to explore genetic and environmental influences on 5-HT metabolism. Brain 5-HT synthesis was estimated by means of positron emission tomography (PET) in combination with the injection of the synthetic analog of the 5-HT precursor tryptophan, alpha-[ 11 C]methyl-L-tryptophan ( 11 C-AMT) [22], [23], [24].…”

N1-Fluoroalkyltryptophan Analogues: Synthesis and in vitro Study as Potential Substrates for Indoleamine 2,3-Dioxygenase

“…[α/β-11 C]-L-Tryptophan, 19,20 5-hydroxy-[α/β-11 C]-L-tryptophan, 20,21 and α-[ 11 C]methyl-L-tryptophan ([ 11 C]AMT) 15,21−23 are radiotracers used essentially in positron emission tomography (PET) studies of the in vivo transport and brain serotonin metabolism of L-tryptophan in health and disease.…”

Measuring serotonin synthesis: from conventional methods to PET tracers and their (pre)clinical implications

“…In another study [106], the authors compared the ability of the PET tracers [ 11 C]5-HTP and [ 11 C]AMT to measure AADC activity in the monkey brain. It appeared that these tracers had different rate constants and accumulation rates.…”