Blood-brain barrier transport and cerebral utilization of dopa in living monkeys

Abstract

[18F]fluoro-dopa, DL-3,4-dihydroxy-5-[18F]fluorophenylalanine, a tracer for dopa, was injected intravenously into cynomolgus monkeys anesthetized with enflurane, and the appearance of 18F in the head and the disappearance of 18F from the blood were each measured continuously for 10 min with simple gamma-ray detectors. A three-compartment explanatory model was used to derive fractional rate constants for the forward flux of L-dopa into the endothelium of the brain capillaries from the blood (1.54 +/- 0.37 min-1), the back flux of dopa and/or its metabolites to the blood from the endothelium (0.67 +/- 0.05 min-1), the formation of dopamine from dopa (0.20 +/- 0.04 min-1), and the destruction of dopamine (0.04 +/- 0.02 min-1). It was also shown that only one-fifth of the dopa that entered the endothelium was available for dopamine synthesis in neurons. It was concluded that the technique described could be extended to man and used to investigate the role of dopa and dopamine in the control of mood and locomotion.