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Biomedical subjects

G Firnau

Publications and source records attributed to G Firnau.

At least 37 records · Page 2Linked to original sources

Cerebral metabolism of 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine in the primate.

The tracers 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine (6-[18F]fluoro-L-DOPA) and L-[14C]DOPA were injected simultaneously into rhesus monkeys, and the time course of their metabolites was measured in the striatum and in the occipital and frontal cortices. In the striatum, 6-[18F]fluoro-L-DOPA was metabolized to 6-[18F]fluorodopamine, 3,4-dihydroxy-6-[18F]fluorophenylacetic acid, and 6-[18F]fluorohomovanillic acid. The metabolite pattern was qualitatively similar to that of L-[14C]DOPA. 6-[18F]Fluorodopamine was synthesized faster than [14C]dopamine. In the frontal cortex, the major metabolite was also 6-[18F]fluorodopamine or [14C]dopamine. In the occipital cortex, the major metabolite was 3-O-methyl-6-[18F]fluoro-L-DOPA. On the basis of these data, the images obtained with 6-[18F]fluoro-L-DOPA and positron emission tomography in humans can now be interpreted in neurochemical terms.

Animals↗

[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.

Animals↗

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

L-[18F] fluorodopa was administered in trace amounts intravenously to healthy control subjects and to patients with Parkinson's disease. Striatal uptake of radioactivity was measured using positron emission tomography. The capacity of the striatum to retain tracer was severely impaired in patients compared to controls. This may reflect a reduction of striatal dopamine storage in Parkinson's disease. Patients showing the "on/off" phenomenon had an even greater decrease of striatal storage capacity.

Adult↗

High yield synthesis of 6-[18F]fluoro-L-dopa.

The radiofluorination of L-dopa with [18F]F2 was investigated with the purpose of improving the yield of 6-[18F]fluoro-L-dopa. When boron trifluoride was added to the reaction mixture in hydrogen fluoride (HF), the yield was increased threefold. Nine millicuries of 6-[18F]fluoro-L-dopa were produced from 100 mCi [18F]F2 routinely and reliably after 2 hr of preparation. If acetonitrile or water were substituted for HF, little or no 6-fluoro-L-dopa was made.

Arsenic↗

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.

Adult↗

Estimation of the radiation dose in man due to 6-[18F]fluoro-L-dopa.

The radiation dose to the organs of the human body after an intravenous administration of 6-[18F]fluoro-L-dopa was estimated using the recommendations of the International Committee on Radiological Protection (ICRP). The bladder wall received the highest dose, 6.95E-10 Sv/Bq (2,600 mrem/mCi), and as a consequence the dose to the genitalia was 1.6E-11 Sv/Bq (60 mrem/mCi). The major organs received a dose of 5.66E-12 to 1.87E-11 Sv/Bq (20 to 60 mrem/mCi). The effective dose equivalent was estimated at 5.39E-11 Sv/Bq (200 mrem/mCi).

Adult↗

Reduced striatal glucose consumption and prolonged reaction time are early features in Huntington's disease.

Striatal glucose consumption was measured by positron emission tomography in 4 male patients, aged 16-27, suffering from Huntington's disease and in 3 age-matched control subjects. Symptoms had been present for 3 years or less; they were mainly psychiatric. Two of the patients had no chorea although the time taken to initiate a movement was prolonged and there was some reduction in the speed at which movements could be executed. Caudate atrophy was absent or minimal by CAT scan yet striatal glucose consumption was markedly reduced in all of the patients. It is suggested that striatal glucose consumption is largely determined by the functional integrity of spiny neurones in the striatum.

Adolescent↗

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.

Adult↗

Aromatic radiofluorination with [18F]fluorine gas: 6-[18F]fluoro-L-dopa.

A new synthesis is described for the routine production of 3,4-dihydroxy-6-[18F]fluoro-phenyl-L-alanine (6-[18F]fluoro-L-dopa). The reaction between [18F]fluorine gas and 3,4-dihydroxyphenyl-L-alanine (L-dopa) in liquid hydrogen fluoride gave 2-, 5-, and 6-[18F]fluoro-L-dopa. 6-[18F]Fluoro-L-dopa was isolated by reverse-phase high-pressure liquid chromatography. From 100 mCi [18F]F2, the method produces 3 mCi of 6-[18F]fluoro-L-dopa at the end of synthesis.

Chromatography, High Pressure Liquid↗

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.

Animals↗

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. Glucose metabolism of grey- and white-matter structures in the brain could be differentiated clearly. Decreased glucose metabolism was identified in regions of the brain shown by computerized axial tomography to be structurally abnormal. Positron emission tomography is a promising new diagnostic tool for the study of newborn infants with suspected abnormalities of brain function.

Brain↗

A positron emission tomograph to study brain metabolism in man.

The construction of a single ring positron emission tomograph with which to examine the brain is described. The ring comprises 160 bismuth germanate detectors that are not separated from each other by high Z septa. The thickness of the slice examined is 2 cm and the inherent resolution is 7 mm in the plane. The performance of the tomograph and representative clinical studies are illustrated.

Bismuth↗