Dopamine visualized in the basal ganglia of living man

Abstract

The neurotransmitter dopamine has biological attributes that make it amenable to study by positron emission tomography, unlike many of the 40 or so neurotransmitters that have been identified in the brain. Dopamine deficiency in the nigrostriatal system is a characteristic of Parkinson's disease, and a disturbance of dopamine metabolism is still widely held to be responsible for the syndrome of schizophrenia. Despite its importance in the regulation of locomotion and mood, it has been impossible to visualize the intracerebral distribution of dopamine and measure its regional metabolism in man. In the first demonstration of the regional distribution of a neurotransmitter in the brain of conscious normal man, we show here that L-3,4-dihydroxyphenylalanine (L-dopa) labelled in the 6-position with the positron-emitting radionuclide fluorine-18, localizes specifically in the dopaminergic pathways of the human brain where its turnover could be measured atraumatically by positron emission tomography.

6-[18F]fluoro-l-DOPA Metabolism in Living Human Brain: A Comparison of Six Analytical Methods

“…Figure 5D compares and R estimates are listed for normal controls and patients with Parkinson's disease in Table 1. (Firnau et al ., 1973 ;Garnett et al, 1983;Cumming et al, 1988). FDOPA , the metabolite OMFD, and a num ber of endogenous amino acids are transported from the circulation to brain tissue by an endothelial membrane transporter of large neutral amino acids (Oldendorf and Szabo, 1976) .…”

Dopamine Storage Capacity in Caudate and Putamen of Patients with Early Parkinson's Disease: Correlation with Asymmetry of Motor Symptoms

“…In FDOPA/PET studies, radioactivity is preferentially retained in the healthy striatum (Garnett et al, 1983), reflecting the formation in situ of [ 18 F]fluorodopamine (Cumming et al, 1987a, b; Endres et al, Figure 3 Mean parametric maps of the magnitude of the effective distribution volume of [ 18 F]fluorodopa (FDOPA) (EDV 2 , ml/g) calculated by a nonlinear method in healthy aged subjects (A) and patients with Parkinson's disease (B), the magnitude of EDV 2 calculated by a multilinear method in healthy aged subjects (C) and patients with Parkinson's disease (D), and the distribution volume of FDOPA (V d , ml/g) calculated by the Logan graphical method in healthy aged subjects (E) and patients with Parkinson's disease (F). Each map is the mean estimate obtained for healthy aged controls (N ¼ 6; left-hand side) and Parkinson's disease patients (N ¼ 8; right-hand side), for whom the parametric maps were flipped so that the most severe motor symptoms were on the right side.…”

Three-Step, “One-Pot” Radiosynthesis of 6-Fluoro-3,4-Dihydroxy-l-Phenylalanine by Isotopic Exchange

“…nine, 6-18 F-fluoro-3,4-dihydroxy-L-phenylalanine (6-18 Ffluoro-L-DOPA), is an established radiotracer for diagnosis of the integrity and function of the nigrostriatal dopaminergic system by PET (1,2). More recently, it was also found that 6-18 F-fluoro-L-DOPA has potential for oncologic diagnosis (3,4), especially in PET studies of neuroendocrine tumors (5).…”