Simplified quantification of dopamine transporters in humans using [Tc-99m]TRODAT-1 and single-photon emission tomography

Quantification of dopamine transporters (DAT) using [Tc-99m]TRODAT-1 and si ngle-photon emission tomography (SPET) requires full kinetic modeling of th e data, using complex and invasive arterial blood sampling to provide an in put function to the model. We have shown previously that a simpler referenc e tissue model provides accurate quantitative results, using a reference re gion devoid of DAT as the input to the model and thereby obviating the need for blood sampling. We now extend this work into humans, and develop furth er simplifications to make the imaging protocol much moro practical as a ro utine procedure, Fourteen healthy subjects (age 29.8+/-8.4 years, range 18. 7-45.5 years) underwent dynamic SPET for 6 h following injection of 752+/-2 8 MBq [Tc-99m]TRODAT-1. The kinetic data were analyzed using nonlinear regr ession analysis (NLRA) and Logan-Patlak graphical analysis. In addition, si mple average ratios of striatal-to-background counts were obtained for thre e l-h periods (3-4 h, 4-5 h, 5-6 h), and compared against the kinetic model s. All methods gave an index of specific binding, proportional to the bindi ng potential, known as the distribution volume ratio (DVR). The reference t issue NLRA gave mean values of k(3) = 0.013+/-0.003 min(-1), k(4) = 0.011+/ -0.002 min(-1), and DVR = 2.29+/-0.17. Graphical analysis gave a value of D VR = 2.28+/-0.16, and the three ratio values of DVR were: 3-4 h, 2.18+/-0.1 5; 4-5 h, 2.34+/-0.13; and 5-6 h, 2.46+/-0.19. Graphical analysis was highl y correlated with NLRA (R-2 = 0.91, slope = 0.90+/-0.08). The ratio methods correlated well with NLRA (3-4 h, R-2 = 0.71, slope = 0.73+/-0.13: 4-5 h, R-2 = 0.86, slope = 0.73+/-0.09; 5-6 h, R-2 = 0.80, slope = 1.00+/-0.15), a nd also with graphical analysis (3-4 h, R-2 = 0.65, slope = 0.74+/-0.16: 4- 5 h, R-2 = 0.85, slope = 0.78+/-0.09; 5-6 h, R-2 = 0.88, slope = 1.11+/-0.1 2). The optimum equilibrium time point Tor obtaining a simple ratio was app roximately 4.5-5.5 h. In conclusion, the simple ratio techniques for obtain ing a quantitative measure of specific binding con-elated well with the ref erence tissue kinetic models, using both NLRA and graphical analysis. The o ptimum time for obtaining a ratio appeared to be in the range 4.5-5.5 h. Ea rlier time points, while still relatively accurate, had a lower sensitivity and may not be optimized for measuring small changes in DAT concentrations .