Gunter Firnau

Striatal dopamine distribution in Parkinsonian patients during life

Eleven neuropsychologically normal Parkinsonian patients were studied with [18F]6-fluoro-L-dopa and positron tomography. In all of the patients dopaminergic activity was reduced in the putamen on the side opposite to the major motor signs. The reduction was similar in tremulous and rigid patients. In contrast dopaminergic activity was normal in the caudate nuclei. It is argued that the putamen is mainly involved in the regulation of movement while the caudate nuclei assume a role in cognitive processes.

Increased frontal and reduced parietal glucose metabolism in acute untreated schizophrenia

Frontal and parietal lobe metabolism was measured by [18F] fluorodeoxyglucose positron emission tomography in 8 never-medicated DSM-III schizophrenic patients and in 10 control subjects. Patients were in a psychotic episode at the time of this scan. Seven of eight had been ill less than 2 years and had only mild neurocognitive impairment. Frontal lobe glucose metabolism was significantly greater in schizophrenic patients than in controls. This finding differs from that of hypofrontality reported in chronic patients previously treated with neuroleptics. Relative glucose metabolism in the interior parietal lobe was significantly lower in schizophrenic patients than in controls. The frontal/parietal ratios were significantly greater in patients than in controls.

Central dopaminergic pathways in hemiparkinsonism examined by positron emission tomography.

[18F]6-fluoro-L-dopa and positron emission tomography has been used to study intracerebral dopamine distribution in five control subjects and six patients with hemiparkinsonism. In the control subjects striatal, frontal and cingulate accumulations were clearly seen. In addition 18F concentrated in the region of the insula and the parietal lobe. In the patients striatal accumulation 18F was reduced in the contralateral striatum, especially in the putamen. The uniformity of distribution of 18F in the striatum on the side of the parkinsonian signs was also irregular. This finding is consonant with the suggestion that intracerebral compensatory mechanisms prevent the manifestation of intracerebral dopamine deficiency from becoming obvious until a late stage of the disease.

Striatal dopamine metabolism in living monkeys examined by positron emission tomography.

Positron emission tomography, using the dopa analogue [18F]6-fluoro-L-dopa, has been used to depict the neostriatum in living monkeys. The amount of 18F that accumulated preferentially in the striatum could be augmented by a peripheral decarboxylase inhibitor. Striatal 18F could also be discharged with reserpine. This is the first time that the regional distribution of a neurotransmitter has been demonstrated in monkeys.

[18F]Fluoro-l-dopa for the in vivo study of intracerebral dopamine

6-[18F]Fluoro-L-dopa was designed to trace the dopamine metabolism in the brain with positron tomography. 6-[18F]Fluoro-L-dopa resembles natural L-dopa biochemically, it crosses the blood-brain barrier with the similar kinetics, it is decarboxylated by dopa decarboxylase and is stored intraneuronally in vesicles. In addition the rate of O-methylation of 6-[18F]fluoro-L-dopa by catechol-O-methyl transferase is only 1/4 of that of natural L-dopa. The low rate of O-methylation, especially in the periphery, is particularly beneficial for PT investigations of the brain. The radiotracer has been synthesized using a variety of electrophilic fluorinating agents.

Radiofluorination with xenon difluoride: A new high yield synthesis of [18F]2-fluoro-2-deoxy-d-glucose

The reaction between [18F]xenon difluoride, 3,4,6-tri-O-acetyl-D-glucal and boron trifluoride in ether gives exclusively [18F )3,4,6-tri-O-acetyl-2-fluoro-2-deoxy-D-glucopyranosyl fluoride, which is hydrolysed with 1 N HCl to [18F]2-fluoro-2-deoxy-D-glucose. The overall chemical yield is 75%; the radiochemical yield is 20%. The procedure takes 45 min.

The Distribution and Kinetics of [18F]6-Fluoro-3-O-methyl-L-dopa in the Human Brain

The analysis of positron tomographic studies of 3,4-dihydroxyphenylethylamine (dopamine) metabolism in which [18F]6-fluoro-l-3,4-dihydroxyphenylalanine (F-dopa) is used as a tracer is confounded by the presence of [18F]6-fluoro-3-O-methyl-l-3,4-dihydroxyphenylalanine (OMFD). This labeled molecule, formed by the action of peripheral cathechol-O-methyltransferase on F-dopa, crosses the blood–brain barrier and contributes to the radioactivity measured by the tomograph. Corrections for this radioactivity in the brain have been proposed. They rely upon the assumption that regional variations in the handling of this molecule by the brain are negligible. Although this assumption is pivotal for the proper quantification of dopamine metabolism using F-dopa, the distribution and kinetics of OMFD have never been studied in humans. We present results in humans that show that there is little selective regional 18F accumulation in the brain, that the distribution volume of OMFD is close to unity, and that a single, reversible compartment is adequate to model the measured time course of radioactivity after an OMFD injection. Analysis of plasma samples for labeled metabolites showed that more than 95% of the radioactivity was associated with OMFD at all times. Our results for OMFD kinetics are in accord with published results obtained in nonhuman primates and for the bidirectional transport of large neutral amino acids across the blood-brain barrier measured using a synthetic amino acid. However, our results also indicate that there are small but significant differences in OMFD kinetics in different parts of the brain that may prevent inferences about the handling of OMFD in one part of the brain from being extended to other parts of the brain.

Regional cerebral glucose metabolism of newborn infants measured by positron emission tomography.

The new diagnostic technique, positron emission tomography with 18F‐2‐fluoro‐2‐deoxy‐D‐glucose (18FDG), was used to measure regional cerebral glucose metabolism in five newborn infants with demonstrated structural abnormalities of the brain. 18FDG was synthesized, diluted in normal saline and injected intravenously. After one hour, tomographic slices of the brain were obtained, the level of the slices being defined relative to the cerebral ventricles.

Dopamine D2 receptors quantified in vivo in human narcolepsy

Assays in brain tissues from humans suffering from narcolepsy, and from genetically narcoleptic dogs have suggested that dopamine function may be disturbed in this condition. We have used the specific D2 receptor ligand N-(3-[18F]fluoropropyl)-spiperone and positron tomography to study a group of 6 well-characterized medication-free, HLA-DR2 DRW15 DW6-positive narcoleptic patients and a group of age- and sex-matched control individuals during life. We found no difference in striatal D2 receptor binding between these two groups. These results suggest that narcolepsy is not associated with alterations in D2 receptor density and affinity.

Why do Tc-99m chelates work for cholescintigraphy?

There are four structural requirements for substances that are excreted by the liver: 1. Their molecular weight is between 300 and 1,000. 2. They are organic anions. 3. They contain at least two ring systems in the molecule. 4. They are bound to serum albumin. All the Tc-99m chelates suggested for cholescintigraphy fulfill these requirements. For the first time a rational for their efficacy is provided.