Brain dopamine metabolism in patients with Parkinson's disease measured with positron emission tomography.

Abstract

2-, 5-and 6-L-[(8F] fluorodopa was used. The relative isomeric proportions were 35, 5 and 60% respectively. The radioactivity, 2-6 mCi, was associated with 8-10 mg L-fluorodopa. The estimated mean specific activity was 103-0 -+ 22-9 mCi/mmol. This mixture was injected intravenously in a volume of 10 ml over two minutes using a constant infusion Harvard pump.Construction of arterial curve A Teflon (gauge 21) cannula was inserted into one radial artery, and 3 ml blood samples were taken at 20 second intervals during the first three minutes following tracer injection, and then every 30 to 60 seconds for a further seven minutes. Arterial sampling times were then gradually spaced out via 5 and 10, to 20 minute intervals. Usually a total of 25 samples were taken. The samples were spun and the concentration of isotopes in plasma was measured in a well-counter cross calibrated with the tomograph.

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

“…We did not find any significant cor relation because of little variation of the plasma OMFD-FDOPA ratio across the subjects (data not shown). Furthermore , the presence of transporter competitors in plasma reduced the accumulation of FDOPA and its metabolites in brain but did not af fect the ratio (Leenders et al, 1986b). We conclude that the striato-occipital ratio is a good index of FDOPA accumulation, especially for those patients who cannot tolerate immobilization.…”

Parkinsonian abnormality of foot strike: a phenomenon of ageing and/or one responsive to levodopa therapy?

“…On the surface this is surprising, since of the four cardinal signs of Parkinsonism, bradycardia, tremor, rigidity and postural abnormality, it is the first, and certainly not the last, which is said to be particularly responsive to levodopa therapy (Cotzias et al, 1969). However, for Parkinsonism to be diagnosed at least two of the four signs (Fahn, 1974;Sweet & McDowell, 1974;Shoulson et al, 1975;Tolosa et al, 1975;Eriksson et al, 1984), who, presumably, have loss of storage capacity for dopamine in the striatum (Leenders et al, 1986). Moreover, Rossor et al (1980) in a placebo controlled, cross-over study, using levodopa without a decarboxylase inhibitor, were able to find a correlation between plasma dopamine concentrations and response in patients defined as not suffering from rapid swings in performance.…”

Direct comparison of FP-CIT SPECT and F-DOPA PET in patients with Parkinson’s disease and healthy controls

“…F-DOPA uptake reflects the activity of aromatic L-amino acid decarboxylase (AADC) in the nerve terminals of the nigrostriatal dopaminergic pathway and the storage of F-dopamine in these nerve terminals [4,5]. FP-CIT binds to DATs, involved in the reuptake of dopamine from the synaptic cleft [11].…”

“…PET scans using 6-[ 18 F]fluoro-L-3,4-dihydroxyphenylalanine (F-DOPA) enable measurement of striatal levodopa decarboxylase activity and trapping of F-dopamine in synaptic vesicles, which are decreased in PD [4][5][6][7][8]. It has been suggested that in the early stages of this disease, levodopa decarboxylase activity is upregulated [9,10], although this has not yet been proved.…”

“…Radiotracer neuroimaging techniques using positron emission tomography (PET) or single photon emission computed tomography (SPECT) can be helpful in visualizing and measuring striatal dopaminergic activity [4,5]. PET scans using 6-[ 18 F]fluoro-L-3,4-dihydroxyphenylalanine (F-DOPA) enable measurement of striatal levodopa decarboxylase activity and trapping of F-dopamine in synaptic vesicles, which are decreased in PD [4][5][6][7][8].…”