Cerebral 6-[F-18]fluoro-L-DOPA (FDOPA) metabolism in pig studied by positron emission tomography

We measured 6-[F-18] fluoro-L-DOPA (FDOPA) uptake and metabolism in the bra in of 4-month-old female pigs (n = 8) using a high-resolution positron emis sion tomograph (PET) in 3D mode. The mean net blood-brain clearance of FDOP A (K-i(D)) to striatum was 0.011 mi g(-1) min(-1). Correcting for the elimi nation of decarboxylated metabolites from striatum (k(loss) = 0.004 min(-1) ) increased the apparent magnitude of the estimate of K-i(D) by 50%, at the expense of doubling the variance of the mean estimate. The mean decarboxyl ation rate of FDOPA in striatum relative to the cerebellum input (k(3)(s)) was 0.008 min(-1). For multicompartmental analyses, the FDOPA partition vol ume (V-e(D)) was constrained to the individual value observed in cerebellum (mean = 0.53 mi g(-1)), with correction for the presence in brain of the p lasma metabolite 3-O-methyl-FDOPA (OMFD). Using the first 60 min of the dyn amic PET scans, the rate constant of FDOPA decarboxylation (k(3)(D)) was es timated to be 0.037 min(-1) in striatum, but was not significantly differen t than zero in frontal cortex. Fitting of a compartmental model correcting for elimination of decarboxylated metabolites to the complete PET frame-seq uence (120 min) increased the variance of the estimate of k(3)(D) in striat um. The magnitude of k(3)(D) in striatum of young pig was less than values estimated previously in neonatal piglet, adult monkey, and human. MRI-based simulations predicted that recovery of radioactivity from pig striatum was highly sensitive to the volume of interest. We conclude that the spatial r esolution of our tomograph reduces the apparent magnitude of k(3)(D) in str iatum. However, anaesthetised pigs are an appropriate experimental model fo r PET studies of DOPA decarboxylation in striatum. Synapse 33:247-258, 1999 , (C) 1999 Wiley-Liss, Inc.