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 tomograph y (PET) in human brain. Dynamic PET data were acquired from young heal thy 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 us ing the Patlak-plot approach. The application of a three-compartment m odel resulted in low identifiability of individual k-values, especiall y that of k(3). Model identifiability analysis using a singular value decomposition of the final sensitivity matrix showed parameter identif iability to increase by 50% when the Patlak-plot approach was used. K- complex values derived by the Patlak-plot approach overestimated the c ompartmental values by 10 to 20%, because of the violation of the dyna mic equilibrium assumption. However, this bias was fairly constant in all structures of the brain. The rank order of K-complex values from d ifferent brain regions corresponded well to the regional concentration s of serotonin in human brain (P < 0.0001). These results indicate tha t the Patlak-plot method can be readily applied to [C-11]AMT data in o rder to create functional images of the K-complex, reflecting serotoni n synthesis rate, within an acceptable error margin.