Microdialysis with radiometric monitoring of L-[beta-11C]DOPA metabolites in rat striatum and plasma

The catecholamine, dopamine (DA), is synthesized from 3,4-dihydroxy-L-phenylalanine (L-DOPA) by aromatic L-amino acid decarboxylase (AADC). DA metabolism is regulated by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). To measure dopaminergic metabolism, we used microdialysis with radiometric detection to monitor L-[beta-11C]DOPA metabolites in the extracellular space of the rat striatum and plasma. We also evaluated the effects of AADC, MAO, and COMT inhibitors on striatal metabolite profiles. L-[beta-11C]DOPA and its radioactive metabolites, [11C]3,4-dihydroxyphenylacetic acid ([11C]DOPAC), [11C]homovanillic acid ([11C]HVA), L-3-O-methyl-[11C]DOPA ([11C]3-OMD) and [11C]3-methoxytyramine ([11C]3-MT) were detected, however [11C]DA was not detected in striatal dialysate following intravenous injection of L-[beta-11C]DOPA. The major early species measured after administration of L-[beta-11C]DOPA were [11C]DOPAC and [11C]HVA in a 1:1 ratio, which shifted toward [11C]HVA with time. An AADC inhibitor increased the uptake of L-[beta-11C]DOPA and [11C]3-OMD and delayed the accumulation of [11C]DOPAC and [11C]HVA. With MAO inhibition, about 80% of total radioactivity was derived from [11C]3-MT. The COMT inhibitor increased [11C]DOPAC and decreased [11C]HVA. L-[beta-11C]DOPA and [11C]3-OMD were detected and then achieved equilibrium in plasma with AADC inhibitor. On the other hand, [11C]3-OMD levels in striatal dialysate decreased significantly following intrastriatal administration of L-[beta-11C]DOPA. These results suggest that [11C]3-OMD in striatal dialysate was generated mostly in peripheral tissue and penetrate into brain. Our results reflect the complicated L-DOPA metabolic pathway, suggesting that this method could improve the understanding of the information obtained from an L-[beta-11C]DOPA PET study or provide an index of dopaminergic metabolism-related neuropsychiatric disorders and evaluation of drug therapies for treatment of the disorder.2010 World Molecular Imaging Congres