VALIDATION OF A LESS-INVASIVE METHOD FOR MEASUREMENT OF SEROTONIN SYNTHESIS RATE WITH ALPHA-[C-11]METHYL-TRYPTOPHAN

We tested in normal human subjects a less invasive method to obtain pl asma input function required in the calculation of the brain serotonin synthesis rate measured with positron emission tomography (PET) and a lpha-[C-11]methyl-tryptophan (alpha-MTrp). The synthesis rates derived with the arterial input function were compared to those derived from venous plasma and venous sinus time-radioactivity curves obtained from dynamic PET images. Dynamic PET images were obtained for the lengths up to 90 minutes after an injection of alpha-MTrp (400 to 800 MBq). In put functions were generated from both artery and vein in three subjec ts, and from artery only in two subjects. Net unidirectional uptake co nstants of alpha-MTrp (K; mL/g/min) were calculated in several brain regions graphically using data between 20 and 60 minutes after injecti on with different input functions. In the five subjects with arterial sampling, we tested two methods for correcting the input functions fro m the venous samples: (1) normalization to the mean exposure time at 2 0 minutes from arterial curve; and (2) the use of the venous sinus cur ve for the first 20 minutes. Venous curves coincided with the arterial ones after about 20 minutes. When the venous curves were used, there was an underestimation of the area under the curves up to 20 minutes, resulting in a 5% to 30% overestimation of K values. Combined use of the sinus curve up to 20 minutes and venous curve from 20 to 60 minute s as an input function resulted in the K (mL/g/min) values larger by 7.1 +/- 3.8% than the K values estimated with the arterial input func tion. Normalization of the venous curve to the exposure time at 20 min utes obtained from the arterial plasma curve resulted in a bias in the K of about -0.34 +/- 3.32%. The bias from the K* values was propagat ed to the serotonin synthesis rates. The use of a combination of the v enous blood samples and venous sinus as the input function resulted in an acceptable bias in the serotonin synthesis rates from the tissue t ime-radioactivity curves generated by PET.