Comparative metabolism of fluorinated 3,4-dihydroxyphenylalanine isomers in aggregating brain cell cultures

Fluorinated analogues of 3,4-dihydroxyphenylalanine (DOPA) were tested for intracellular metabolic conversion in aggregating cell cultures prepared from fetal rat brain. 5-Fluoro-D/L-DOPA was methylated almost exclusively to 3-O-methyl-5-fluoro-D/L-DOPA. Metabolism of 6-fluoro-D/L-DOPA resulted in 6-fluorodopamine, 6-fluoro-3,4-dihydroxyphenylacetic acid, and 3-O-methyl-6-fluoro-D/L-DOPA, but with a qualitatively and quantitatively different metabolite pattern compared with that of L-DOPA and D/L-DOPA, respectively. Homovanillic acid and fluorohomovanillic acid have not been found intracellularly in the cultures. On the basis of these data, the model development of the cerebral metabolism of tracers used in positron emission tomography can be improved.