Blood-brain barrier and neuronal membrane transport of 6-[ 18F]fluoro- l-DOPA

Abstract

The transport of 6-[ 18F]fluoro- l-3,4-dihydroxyphenylalanine ([ 18F]FDOPA) across the blood-brain barrier (BBB) and neuronal membranes was compared with that of l-3,4-dihydroxyphenylalanine ( l-DOPA) in rats. The carotid injection method was used as a direct measurement of [ 18F]FDOPA, 1-[ 14C]- l-DOPA, and 3-[ 14C]- l-DOPA transport across the BBB, while isolated nerve terminals were used to examine neuronal membrane transport of [ 3H]- l-DOPA. [ 18F]FDOPA appeared to use the same large neutral amino acid carrier for BBB transport as l-DOPA and l-phenylalanine. In addition, carbidopa [ l-α-hydrazino-α-methyl-β-(3,4-dihydroxyphenyl)propionic acid] was found not to have direct interference with the transport carrier on the BBB, but indirectly inhibited aromatic l-amino acid decarboxylase (AAAD) activity in brain endothelium by depletion of pyridoxal phosphate, a necessary cofactor of the enzyme. In striatal and cortical synaptosomes, [ 3H]- l-DOPA uptake was inhibited by non-radioactive l-DOPA, FDOPA, and 6-fluoro- l- meta-tyrosine (6-FMT). The inhibition was significantly greater in terminals isolated from the striatum than in those from the cerebral cortex. FDOPA, 6-FMT, and l-DOPA equally inhibited the neuronal transport of [ 3H]- l-DOPA. This suggests that FDOPA and 6-FMT compete with l-DOPA at similar transport sites at the neuronal membrane.