Active [3H]-dopamine uptake displayed by native lymphocyte suspensions is mainly due to contaminating platelets

Abstract

The use of animals with large brains has technical, economic, and ethical ramifications in neuroscience. The aims of this study were (1) to determine the suitability of the pig as an experimental model in brain research and (2) to establish normal values of [18F]fluoroDOPA (FDOPA) uptake and metabolism in the brain of the pig. Female Danish country-bred pigs were scanned dynamically using FDOPA and the Siemens/CTI ECAT EXACT HR47 positron emission tomography (PET) scanner. Volumes of interest were identified by region growing from the maximum value of striatal activity. They contained all connected voxels with greater than 90% of the maximum voxel activity. The FDOPA net influx rate constant (K3s) was calculated for the striatum and frontal cortex, using the cerebellum as reference and multiple-time graphical analysis, and was found to be 0.0079 ± 0.001 (min−1). In striatum the net plasma clearance rate K[=K1Dk3D/(k2D+k3D)] at steady state equaled 0.0077 ± 0.0009 (ml g−1min−1). In striatum the unidirectional tracer transfer coefficient (K1D)was 0.029 ± 0.003 (ml g−1 min−1), and the metabolic rate constant (K3D) was 0.018 ± 0.002 (min−1). These parameters were estimated by multicompartmental analysis using the individual estimates of the cerebellum partition (Ve) and striatal plasma (Vp) volumes, corrected for the presence of [18F]3-O roDOPA. Results show that anesthetized pigs are appropriate experimental animals for PET imaging of decarboxylation in the living brain. The striatal DOPA decarboxylation rate was found to range between those of rats and humans and to be equal to the rate constants found in primates. Results suggest that the partial volume effect in the striatum is directly related to the size of the striatum.