KINETIC MODELING OF [C-11] RACLOPRIDE - COMBINED PET-MICRODIALYSIS STUDIES

The in vivo binding of D-2 receptor ligands can be affected by agents that alter the concentration of endogenous dopamine. To define a more explicit relation between dopamine and D-2 receptor binding, the conve ntional compartment model for reversible ligands has been extended to account for a time-varying dopamine pulse. This model was tested with [C-11]raclopride positron emission tomography and dopamine microdialys is data that were acquired simultaneously in rhesus monkeys. The micro dialysis data were incorporated into the model assuming a proportional relation to synaptic dopamine. Positron emission tomography studies u sed a bolus-plus infusion tracer delivery with amphetamine given at 40 minutes to induce dopamine release. The extended model described the entire striatal time-activity curve, including the decrease in radioac tivity concentration after an amphetamine-induced dopamine pulse. Base d on these results, simulation studies were performed using the extend ed model. The simulation studies showed that the percent decrease in s pecific binding after amphetamine measured with the bolus-plus-infusio n protocol correlates well with the integral of the postamphetamine do pamine pulse. This suggests that changes in specific binding observed in studies in humans can be interpreted as being linearly proportional to the integral of the amphetamine-induced dopamine pulse.