Comparative in vivo metabolism of 6-[18F]fluoro-l-DOPA and [3H]l-DOPA in rats
| Autor: | Milton M. Perlmutter, Charna H. K. Nissenson, A. Luxen, Michael E. Phelps, Jorge R. Barrio, William P. Melega |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Male
Fluorine Radioisotopes Cerebellum medicine.medical_specialty Central nervous system Striatum Tritium Biochemistry Levodopa Dopamine In vivo Internal medicine Blood plasma medicine Animals Chromatography High Pressure Liquid Pharmacology Chemistry Brain Carbidopa Rats Inbred Strains Metabolism Dihydroxyphenylalanine Rats Kinetics medicine.anatomical_structure Endocrinology Injections Intravenous medicine.drug |
| Zdroj: | Biochemical Pharmacology. 39:1853-1860 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/0006-2952(90)90601-g |
| Popis: | In vivo double-label experiments in rats were designed to correlate the peripheral and cerebral metabolism of 6-[18F]fluoro-L-DOPA [( 18F]FDOPA) with that of [3H]L-DOPA. Authentic samples of the major [18F]FDOPA metabolites were synthesized to identify the 18F-labeled metabolites. After carbidopa pretreatment and intravenous administration of the compound, the products of peripheral metabolism in plasma were analyzed at times from 3 to 60 min. In the periphery, amine conjugates were detected but they accounted for less than 15% of the total radioactivity; the major metabolites were 3-O-methyl-6-[18F]fluoro-L-DOPA and 3-O-methyl-[3H]L-DOPA. The rate and extent of 3-O-methylation of [18F]FDOPA exceeded that of [3H]L-DOPA. Both 3-O-methylated products entered the striatum and cerebellum where they contributed significant but uniform activity. Analysis of cerebral metabolism in these structures indicated a linear accumulation of total radioactivity: a striatum/cerebellum ratio of 2 was observed by 60 min. 6-[18F]Fluorodopamine (35%) and [3H]dopamine (55%) were the major metabolites formed in the striatum: however, the methylated [18F]FDOPA and [3H]DOPA products of predominantly peripheral origin represented 55% (18F) and 35% (3H) of the total radioactivity respectively. Other [3H]dopamine metabolites and their 18F-labeled analogs represented less than 10-15% at all times analyzed. The cerebellum radioactivity was composed only of [18F]FDOPA, [3H]DOPA and their 3-O-methylated products. These data will serve as the basis for the development of kinetic models of [18F]FDOPA metabolism that can be applied to the evaluation of central dopamine biochemistry with positron emission tomography in humans. |
| Databáze: | OpenAIRE |
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