Quantification of dopamine metabolism in man: a mathematically justifiable approach

Model derivation, the proposal of the best model to fit the measured data, is a crucial and often neglected step in compartmental analysis. Since the model which best fits the data in a statistical sense may be simpler than the known physiology of the system, the order (mathematical complexity) of the model that can be accepted must be determined independently of physiological considerations. Although [18F]6-fluoro-L-dopa (F-dopa) has been used as a tracer for the investigation of presynaptic dopamine metabolism for a number of years, a definitive method of quantitative analysis has not yet emerged. Simple graphical analyses have been used predominantly in clinical studies, while compartmental analyses have been used to gain a better understanding of F-dopa kinetics. Over the years quantitative approaches to F-dopa metabolism have grown increasingly complicated, and complex models that rely on the use of parameter constraints, or simplifying assumptions in order to collapse the model to solvable dimensions, have been developed. We propose a simple compartmental model to quantify the metabolism of F-dopa in the striatum. Both compartmental and graphical analyses were performed using this model, and the mathematical expression which relates the results of the two analyses was derived. The ability of our approach to reveal and quantify differences in the dopaminergic metabolism of individuals has been demonstrated in a small number of studies.