The Cerebral Metabolism of L-Dihydroxyphenylalanine

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Abstract
The regional cerebral distribution of carbon-14 activity was studied using auto-radiography following the intravenous administration of L-3,4-dihydroxyphenyl-(3-14C)-ala-nine (14C-L-dopa) to rats pretreated with carbidopa. 5 min after 14C-L-dopa administration, the regional cerebral distribution of carbon-14 varied with regional cerebral blood flow. From 45 min to 4 h after 14C-L-dopa administration, however, carbon-14 activity accumulated in a regionally selective manner which correlated (p < 0.001) with the total endogenous catechol-amine content of each region (n = 26). A prior unilateral lesion of the substantia nigra pars compacta markedly reduced the accumulation of carbon-14 in the ipsilateral, but not the contralateral, striatum at all times from 45 min to 4 h after 14C-L-dopa administration. Similarly, reserpine pretreatment selectively reduced the accumulation of carbon-14 in only those regions in which a marked accumulation occurred in controls after intravenous injections of 14C-L-dopa. Liquid chromatography with electrochemical detection was utilized to determine the tritium content of L-dopa and its metabolites in the striatum and cerebellum from 1 min to 4 h after the intravenous administration of 3H-L-dopa. 3H-dopamine, and subsequently 3H-dihydroxyphenylacetic acid and 3H-homovanillic acid, appeared only in the striatum. 3H-3-O-methyldopa levels rose simultaneously in the cerebellum and striatum. These results demonstrate a feasible approach for imaging dopamine neurons in man in vivo by positron emission tomography provided that L-dopa can be labeled with a positron-emitting isotope with sufficient specific activity. Furthermore, these results suggest that quantitative interpretation of the images is possible.