A Reversible Tracer Analysis Approach to the Study of Effective Dopamine Turnover

Abstract

Changes in dopamine turnover resulting from disease states such as Parkinson's disease may be reflected in corresponding changes in the kinetics of the positron emission tomographic tracer [¹⁸F]fluorodopa. The authors had previously refined the conventional irreversible-tracer graphical approach to determine both the uptake rate constant K_i and the rate constant k_loss that describes the slow loss of the trapped kinetic component. Because these parameters change in the opposite sense with disease, their ratios may be more powerfully discriminating than either one alone. The ratio k_loss/K_i is indicative of effective dopamine turnover. Its inverse, K_i/k_loss, can be interpreted as the effective distribution volume (EDV) of the specific uptake compartment referred to the fluorodopa concentration in plasma. Here the authors present a new approach to the estimation of EDV based on reversible-tracer graphical methods. When implemented with a plasma input function, the method evaluates EDV directly. When implemented with a tissue input function, the outcome is proportional to the ratio of the distribution volumes of the specific uptake and precursor compartments. Comparison of the new and previous approaches strongly validates this alternative approach to the study of effective dopamine turnover.