Analysis of [C-11]alpha-methyl-tryptophan kinetics for the estimation of serotonin synthesis rate in vivo.
We describe the tracer kinetic analysis of [C-11]-labeled alpha-methyl-tryptophan (AMT), an analogue of tryptophan, which has been developed as a tracer for serotonin synthesis using positron emission tomography (PET) in human brain. Dynamic PET data were acquired from young healthy volunteers (n = 10) as a series of 22 scans covering a total of 60 minutes and analyzed by means of a three-compartment, four-parameter model. In addition, functional images of the K-complex were created using the Patlak-plot approach. The application of a three-compartment model resulted in low identifiability of individual k-values, especially that of k3. Model identifiability analysis using a singular value decomposition of the final sensitivity matrix showed parameter identifiability to increase by 50% when the Patlak-plot approach was used. K-complex values derived by the Patlak-plot approach overestimated the compartmental values by 10 to 20%, because of the violation of the dynamic equilibrium assumption. However, this bias was fairly constant in all structures of the brain. The rank order of K-complex values from different brain regions corresponded well to the regional concentrations of serotonin in human brain (P < 0.0001). These results indicate that the Patlak-plot method can be readily applied to [C-11]AMT data in order to create functional images of the K-complex, reflecting serotonin synthesis rate, within an acceptable error margin.
Muzik
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Department of Radiology, Wayne State University, Children's Hospital of Michigan, Detroit, USA.
Chugani
D C
DC
Chakraborty
P
P
Mangner
T
T
Chugani
H T
HT
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D005240:Feasibility Studies; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D016014:Linear Models; D012016:Reference Values; D012701:Serotonin / Q000096:biosynthesis*; D013788:Thalamus / Q000378:metabolism; D014055:Tomography, Emission-Computed; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism
C020774:alpha-methyltryptophan; D012701:Serotonin; D014364:Tryptophan