Quantitative analysis of dopamine synthesis in human brain using positron emission tomography with L-[β-11C]DOPA

Abstract

To estimate the presynaptic function of the central dopaminergic system, the rate of endogenous dopamine synthesis has been measured by using L-[beta-C]DOPA or 6-[F]fluoro-L-DOPA with positron emission tomography. However, the regional kinetics of L-[beta-C]DOPA in human brain have not been investigated in detail. In the present study, the regional kinetics of L-[beta-C]DOPA in normal human brain and the accuracy of the method for quantifying L-[beta-C]DOPA kinetics, employing reference regions, were investigated. After intravenous injection of L-[beta-C]DOPA, dynamic scanning was performed on ten healthy subjects for 89 min. The overall uptake rate constant K was calculated by the kinetic and graphical approaches, in which the occipital cortex was used as a reference brain region. Regional distribution of K was similar to those of dopamine D2 receptor. A significant negative correlation was observed between the neutral amino acid concentration in plasma and the influx rate constant through the blood-brain barrier (K1). The K values calculated by graphical approach were in good agreement with the values calculated by kinetic approach for both experimental and simulated data. The regional distribution of K corresponds to that of the nigrostriatal and mesolimbic dopaminergic system. Negative correlation between neutral amino acid concentration and K1 supports the suggestion that L-DOPA is transported in a competitive fashion via the same carrier system as neutral amino acids at the blood-brain barrier. Because the graphical approach can obviate the need for an arterial input function, it is useful for investigating the rate of regional dopamine synthesis in neuropsychiatric and neurodegenerative diseases.