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Biomedical subjects

M J Adam

Publications and source records attributed to M J Adam.

25 records · Page 2Linked to original sources

Synthesis and murine tissue uptake of sodium [18F]fluoroacetate.

Fluoroacetate (FAc) is well known as the rodenticide "1080" and for its potent biochemical properties, but much less is known about its behavior in vivo. In order to study this behavior, the compound was labeled with 18F. The synthesis was accomplished in good yields (30%) from carrier-added radiofluorine gas by its conversion to [18F]tetrabutylammonium fluoride, followed by a heat-assisted halogen exchange with ethylbromoacetate. The isolated ester was rapidly and quantitatively hydrolysed with base to form [18F]FAc. preliminary studies in mice revealed relatively little soft tissue retention over the 4 h study period. However, substantial bone accumulation, indicative of defluorination, occurred to a significant degree.

Animals↗

PET studies of cerebral glucose metabolism in idiopathic torticollis.

Regional cerebral glucose metabolism was studied in 16 patients with idiopathic torticollis, using positron emission tomography. Analysis of subcortical regions revealed no consistent focal abnormality of cerebral metabolic rate for glucose, but there was a bilateral breakdown of the normal relationships between the thalamus and basal ganglia. The findings suggest disruption of the pallidothalamic projections in this focal dystonia and may imply a disturbance of GABA.

Adult↗

Positron emission tomography in the early diagnosis of Huntington's disease.

We studied 10 patients with early Huntington's disease and 7 normal age-matched controls with positron emission tomography (PET) using fluorodeoxyglucose. Subjects had little or no caudate nucleus atrophy and had not received any medications. The results demonstrated that hypometabolism of glucose preceded tissue loss. Furthermore, patients with minimal neurologic or psychiatric symptoms and no obvious CT changes may be differentiated from normal persons with high accuracy by PET. PET is helpful in the early diagnosis of Huntington's disease irrespective of the mode of presentation. PET may also be useful for preclinical detection and may supplement information from DNA studies.

Adolescent↗

Routine synthesis of L-[18F]6-fluorodopa with fluorine-18 acetyl hypofluorite.

The synthesis of L-[18F]6-fluorodopa (2.4-10.6 mCi) was done by passing gaseous [18F]acetyl hypofluorite through a solution of L-methyl-N- acetyl-[beta-(3-methoxy-4-acetoxyphenyl)]alaninate in acetic acid at room temperature followed by the hydrolysis of the intermediate products with concentrated hydriodic acid. The desired fluorodopa isomer was isolated in 8% EOB radiochemical yield by high performance liquid chromatography in an overall synthesis time of 100 min.

Acetates↗

The use of C-18 SEP PAK cartridges to simplify routine production of 2-deoxy-2-[18F]fluoro-D-glucose.

The synthesis of 2-deoxy-2[18F]fluoro-D-glucose has been simplified by the use of C-18 SEP PAK cartridges. The fluorinated sugar produced from the reaction of acetyl hypofluorite and tri-acetyl glucal (TAG) was extracted from the neutralized reaction mixture with C-18 SEP PAK cartridges. The product was washed off the cartridge with diethyl ether and hydrolyzed by HCl. After hydrolysis the product was purified by passage through ion retardation resin, alumina and another C-18 cartridge. The radiochemical purity was 98% and the radiochemical yield was 28%, decay corrected to EOB, with a total synthesis time of 50 min from EOB.

Deoxy Sugars↗

Cerebral glucose metabolism in Parkinson's disease.

Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using 18F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra.

Aged↗

Positron emission tomography after MPTP: observations relating to the cause of Parkinson's disease.

The dopa analogue 6-fluorodopa (6-FD) used with positron emission tomography (PET) allows in vivo visualization of dopamine and its metabolites in nigrostriatal nerve endings. We have now found abnormal 6-FD scans in four subjects exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). None had parkinsonism. The results suggest subclinical damage to the nigrostriatal pathway. This is the first direct evidence that dopaminergic impairment can exist without clinical deficits. Here we discuss this finding in the context of the hypothesis that Parkinson's disease may stem from clinically silent damage to the substantia nigra, followed by slow attrition of neurones in this region because of its particular vulnerability to cell loss as a normal consequence of ageing.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗