THE KINETIC-BEHAVIOR OF [H-3]DOPA IN LIVING RAT-BRAIN INVESTIGATED BYCOMPARTMENTAL MODELING OF STATIC AUTORADIOGRAMS

The kinetic behaviour of [H-3]DOPA in living rat brain was investigate d by compartmental modelling of measured activities from combined meta bolite pools in a time-series (180 min) of static autoradiograms from right cerebral hemispheres. Two models of [H-3]DOPA uptake and metabol ism that incorporated the removal of the decarboxylation product, [H-3 ]dopamine, from brain were significantly more accurate than a model in which [3H]dopamine accumulated irreversibly in situ. Present estimate s of [H-3]DOPA kinetic constants were compared to previously published results based on the analysis of measured activities from individual metabolite pools separated by chromatographic fractionation of [H-3]DO PA metabolites in the left cerebral hemispheres of the same rats. Auto radiographic estimates of DOPA decarboxylase activity with respect to [H-3]DOPA in brain (k(3)(DOPA)) were under-estimated several-fold rela tive to chromatographic estimates; this discrepancy is explained by po st-mortem enzyme activity and omission of biological compartments from the models. However, autoradiographic estimates of the unidirectional blood-brain clearance of [H-3]DOPA (K-1(DOPA)) and monoamine oxidase activity with respect to [H-3]dopamine in brain (k(7)(DA)) agreed with chromatographic estimates. This concordance represents the first empi rical validation of compartmental modelling of autoradiographic data a s a method for quantitatively investigating the kinetic behaviour of r adiolabelled L-DOPA in living mammalian brain. (C) 1997 Elsevier Scien ce B.V.