PET examination of the monkey heart with high specific radioactivity [11C]norepinephrine and [11C]metaraminol.
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Adrenergic Uptake Inhibitors↗
Biomedical subjects
T Suhara
Publications and source records attributed to T Suhara.
Hypersensitivity of cortical muscarinic receptors in Parkinson's disease demonstrated by PET.
The status of muscarinic receptors (mAChRs) is not clear in Parkinson's disease (PD). We measured mAChR binding in the brain of eight patients with PD and eight, age-matched, healthy controls by positron emission tomography (PET) and [11C]N-methyl-4-piperidyl benzilate ([11C]NMPB). PD patients were not demented according to DSM III criteria but showed significant frontal lobe dysfunction in the Modified Wisconsin Card Sorting Test. A mean K3 value, which is an index of mAChR binding calculated by a graphical method, was 20% higher in the frontal cortex of PD patients than controls (p < 0.05). Hypersensitivity of mAChRs in the frontal cortex of PD patients may be a response to a loss of ascending cholinergic input to that region, and may relate to frontal lobe dysfunction in PD.
Aged↗
Carbon-11-FLB 457: a radioligand for extrastriatal D2 dopamine receptors.
UNLABELLED: D2 dopamine receptors in extrastriatal brain regions are of central interest for research in schizophrenia and antipsychotic drugs. This article reports the development of [11C]FLB 457 for PET examination of extrastriatal D2 dopamine receptors. METHODS: Carbon-11-FLB 457 was prepared by O-methylation of FLB 604 (2-hydroxy precursor) with [11C]methyl iodide. Total radiochemical yield was 25%-35% within a total synthesis time of 30 min. The specific radioactivity at the end of synthesis was about 1300 Ci/mmole (48 GBq/mumole). RESULTS: FLB 457 bound with high affinity to D2 and D3 dopamine receptors, whereas binding to other putative central receptors was negligible. PET studies in Cynomolgus monkeys demonstrated 15 times higher accumulation of radioactivity in the striatum than in the cerebellum after 60 min. Uptake in the thalamus and neocortex, extrastriatal regions with a low density of D2 dopamine receptors, was, respectively, 4 and 2.5 times higher than in the cerebellum. Radioactivity was displaced by raclopride and haloperidol which confirms the selectivity and reversibility of [11C]FLB 457 binding to D2 dopamine receptors in vivo in the striatum, thalamus and neocortex. CONCLUSION: Carbon-11-FLB 457 should be a useful PET ligand for quantitative examination of D2 dopamine receptors in extrastriatal regions in the human brain.
Animals↗
PET study of [11C]beta-CIT binding to monoamine transporters in the monkey and human brain.
The cocaine congener beta-CIT has been labeled with 11C for positron emission tomographic (PET) studies of the dopamine transporter. In the present autoradiographic study on human brain sections and PET study on monkey and human [11C]beta-CIT accumulated markedly in the striatum. [11C]beta-CIT binding in the striatum was selective to the dopamine transporter. The binding in the thalamus was on an intermediate level and was displaced by compounds having affinity for norepinephrine and serotonin transporters. The neocortical binding was on a low level and could be displaced only by citalopram, a serotonin uptake inhibitor. A high dose of cocaine intravenously (7 mg/kg) induced a 50% occupancy of specific [11C]beta-CIT binding to the dopamine transporter in the striatum. This dose is much higher than the doses of 0.25-0.5 mg/kg i.v. for cocaine arousal in human subjects. The finding indicates that cocaine arousal may be induced at a low dopamine transporter occupancy of a few percent. [11C]beta-CIT should be a useful radioligand to explore cocaine actions in humans and to follow the pathophysiological process in vivo by PET in neurodegenerative diseases of the striatum.
Adult↗
Positron emission tomography shows high specific uptake of racemic carbon-11 labelled norepinephrine in the primate heart.
(-)-Norepinephrine is the predominant neurotransmitter of the sympathetic innervation of the heart. Racemic norepinephrine was labelled with carbon-11 and injected i.v. into Cynomolgus monkeys. Five minutes after injection there was a more than tenfold higher radioactivity in the heart than in adjacent tissue. Pretreatment with the norepinephrine reuptake inhibitor desipramine reduced the uptake by more than 80%. The high specific uptake of racemic [11C]norepinephrine indicates that enantiomerically pure (-)-[11C]norepinephrine has promising potential for detailed mapping of the sympathetic innervation of the human myocardium.
Animals↗
Dopamine D1 receptor number--a sensitive PET marker for early brain degeneration in Huntington's disease.
D1-dopamine receptor binding in the brain was determined by positron emission tomography (PET) in five patients with Huntington's disease, in one asymptomatic gene carrier and in five control subjects. [11C] SCH 23390 was used as the radioligand. Brain morphology was recorded by MRI. The patients who all had a mild to moderate functional impairment showed an almost 50% reduction of putamen volume as well as D1-dopamine receptor density as compared to the controls. The total D1-dopamine receptor number in the putamen was reduced by 75% in the patient group. A similar reduction was found for the caudate nucleus. The asymptomatic gene carrier had volume and density values in the lower range of the control subjects. In the frontal neocortex there also tended to be a reduced D1-dopamine receptor binding in the symptomatic patients. The results indicate that [11C] SCH 23390 binding in combination with MRI can be used as a sensitive marker for early brain degeneration in Huntington's disease. This marker may be useful to monitor the pathophysiological effect of the disease gene and also to follow therapeutic interventions aiming at preventing the degenerative process.
Adult↗
An acute effect of triazolam on muscarinic cholinergic receptor binding in the human brain measured by positron emission tomography.
An acute effect of triazolam, a potent benzodiazepine agonist, on cholinergic receptor binding in the human brain was measured by PET (positron emission tomography) using [11C]N-methyl-4-piperidylbenzilate ([11C]NMPB), a potent muscarinic cholinergic receptor antagonist. Two PET scans were performed in each subject: (1) control scan; (2) after oral administration of 0.5 mg triazolam or placebo. The previously discussed amnestic effect of triazolam was measured by immediate and delayed recall of meaningful and meaningless syllables. A compartment model employing the radioactivity in the cerebellum as an input function was used for the quantification of receptor binding. The binding parameter, k3, was decreased after triazolam administration in all measured regions, whereas no change was observed after placebo treatment. The reduction compared to the control study varied from 8.6 +/- 3.7% in the temporal cortex to 16.3 +/- 6.3% in the thalamus. Triazolam administration impaired both immediate and delayed recall of syllables, whereas placebo administration had no effects. Benzodiazepine agonists are reported to decrease the cortical acetylcholine release. The decrease of acetylcholine release in the synaptic cleft might be the explanation for the decreased binding of [11C]NMPB.
Adolescent↗
Effects of trihexyphenidyl and L-dopa on brain muscarinic cholinergic receptor binding measured by positron emission tomography.
The effects of pharmacological intervention on brain muscarinic cholinergic receptor (mAChR) binding were assessed in seven patients with Parkinson's disease by positron emission tomography and carbon-11 labelled N-methyl-4-piperidyl benzilate ([11C]NMPB). [11C]NMPB was injected twice, approximately 2 hours apart, in each patient, to assess the effect of single doses of 4 mg of trihexyphenidyl (n = 5) or 400 mg of L-dopa with 57 mg of benserazide (n = 2) on the binding parameter of mAChRs (K3). There was a mean 28% inhibition of K3 values in the brain in the presence of trihexyphenidyl, which was assumed to reflect mAChR occupancy. No significant change in K3 was observed in the presence of L-dopa. This study demonstrates the feasibility of measuring mAChR occupancy by an anticholinergic medication with PET.
Aged↗
Intracranial bullet retained since the Sino-Japanese war manifesting as hallucination--case report.
A 69-year-old male with an intracranial bullet retained in the right occipital lobe for 45 years presented with epileptic seizure occasionally accompanied by visual hallucinations. Neurological examination revealed left homonymous hemianopsia and right hearing loss, and electroencephalography showed slow discharges localized in the lesion. The bullet was removed together with the thickened fibrous capsule. His postoperative course was uneventful, and he has become seizure-free. The bullet caused metal toxicity and progressive gliosis, which caused the epileptogenetic focus and associated hallucinations.
Aged↗
No age-related changes in human benzodiazepine receptor binding measured by PET with [11C]Ro 15-4513.
The effects of age on the binding of [11C]Ro 15-4513, a partial inverse agonist of the central benzodiazepine receptor, were studied. Sixteen healthy male volunteers (21-78 years old) participated. Regional radioactivity in the brain was followed for 45 min by positron emission tomography after a bolus injection of [11C]Ro 15-4513. Similar tracer kinetics were observed in both young and old subjects. For the quantification of receptor binding in vivo, a compartment model, in which radioactivity in the pons was used as an input function, was applied. There were no significant changes in the binding potentials with age (P > 0.1) in ten brain regions. These observations delineate an interesting difference between central benzodiazepine (BZ) receptors and other neurotransmitter receptors in the human brain measured by PET that have been shown to have a reduction with age.
Adult↗
Age-related changes in human muscarinic acetylcholine receptors measured by positron emission tomography.
The effects of age on the binding parameters of [11C]N- methyl-4-piperidylbenzilate ([11C]NMPB), a specific muscarinic cholinergic receptor ligand, were studied. Eighteen healthy male volunteers (18-75 years old) participated. Regional radioactivity in the brain was followed for 60 min by positron emission tomography (PET). Uptake of [11C]NMPB continuously increased in all brain areas with the exception of the cerebellum. For the quantification of receptor binding, a compartment model, in which radioactivity in the cerebellum was used as an input function, was used. The binding parameter, K3, of muscarinic acetylcholine receptors in eight brain regions (pons, hippocampus, frontal cortex, striatum, temporal cortex, thalamus, occipital cortex, parietal cortex) showed an age-related decrease of about 45% over the age range.
Adolescent↗
Dopamine D1 receptors in Parkinson's disease and striatonigral degeneration: a positron emission tomography study.
Striatal dopamine D1 receptors were investigated in 11 patients with Parkinson's disease (PD), five patients with striatonigral degeneration (SND) and six age-matched controls by positron emission tomography and carbon-11 labelled SCH23390. The SND patients showed mean 12%, 21%, and 31% declines in the ratios of radioactivity in the caudate, anterior putamen, and posterior putamen compared with that in the occipital cortex. These ratios were not significantly altered in the PD patients. The results may explain the different therapeutic responses to levadopa between SND and PD patients, and this technique might prove useful for their differentiation.
Adult↗
[A new headholder for positron emission tomography].
We developed a new headholder for the fixation and repositioning of patient head in PET study. The device consists of acryl frame and headrest of thermoplastic resin. Special gel is placed on the headrest to adapt different shape of occipit a in each patient. Individual face mask was made with thermoplastic resin just before the PET study and was fixed with the holder using plastic taper. It took about 2-3 min to fix the patient head using these system. Immobilization of the patient's head during PET study was good. Accuracy of repositioning in the same patient was relatively good between separate PET studies.
Evaluation Studies as Topic↗
In vivo binding of [11C]Ro15-4513 in human brain measured with PET.
Ro15-4513, an azide derivative of benzodiazepine antagonist flumazenil (Ro15-1788), and Ro15-1788 were labelled with carbon 11. Sequential PET scans following injection of [11C]Ro15-4513 or [11C]Ro15-1788 into normal male healthy volunteers were measured, and kinetic analysis using pons as a reference region was performed. [11C]Ro15-4513 was highly accumulated in frontal cortex, temporal cortex, hippocampus and relatively lower accumulation in occipital cortex, whereas almost homogeneous distribution of Ro15-1788 throughout cortex area was seen. The kinetic analysis revealed that such differences of regional distribution in brain between two labelled ligands were mainly due to the regional difference of the dissociation rate constants in vivo (k4). [11C]Ro15-4513 may be a useful tool for the in vivo study of benzodiazepine receptors in human brain.
Adult↗
D1 dopamine receptor binding in mood disorders measured by positron emission tomography.
D1 dopamine receptor binding in mood disorders was studied by positron emission tomography (PET) using 11C-SCH23390. Ten patients with bipolar mood disorders and 21 normal controls were studied in the drug-free state. The patients were in euthymic (N = 6), depressed (N = 3) and manic (N = 1) states. Regional radioactivity in the brain was followed for 40 min by PET. A two-compartment model was used to obtain the binding potential (k3/k4) for the striatum and frontal cortex. The binding potentials for the frontal cortex for the patients were significantly lower than those for normal controls, whereas those for striatum were not significantly different. These findings suggest that D1 dopamine receptors in the frontal cortex may be in a different state in patients with bipolar mood disorders.
Adult↗
Effect of sedative drugs upon receptor binding in vivo.
Acute treatment with pentobarbital (PB), ethanol and flunitrazepam significantly decreased 3H-SCH 23390 binding in mouse striatum in a dose dependent manner. In contrast, no significant alterations in 3H-SCH 23390 binding in the cerebral cortex have been observed in mice treated with these sedative and hypnotic drugs. Flumazenil Ro15-1788) reversed the effect of flunitrazepam suggesting the reduction in dopamine D1 receptor binding in the striatum was mediated via GABA-Bz-Cl channel complex. Using kinetic analysis, it was found that such changes in dopamine D1 receptor binding in vivo were mainly due to changes in rates of ligand-receptor binding in vivo. Other non-site-specific drugs such as propanol and butanol also decreased 3H-SCH 23390 binding in vivo, depending on their lipophilicities. These results indicated that micro-environmental factors surrounding receptors, including cell membranes seem to have important roles in receptor binding in vivo. Both PB and flunitrazepam decreased muscarinic acetylcholine receptor binding in mouse cortex, striatum, hippocampus and other regions. Together with the fact that PB also altered 3H-Ro15-1788 binding in vivo, this suggested global changes in microenvironmental factors may occur due to these sedative drugs. In vivo quantitative analysis of neuroreceptors with positron emission tomography (PET) seems to have some potencies to reveal the neurochemical base of benzodiazepine dependence.
Animals↗
[Pulmonary kinetics of 13N-ammonia in smoking subjects--a quantitative study using dynamic PET].
To evaluate the effect of smoking on nonrespiratory function in the lung, a dynamic PET with 13NH3 in the lung was performed in 18 normal volunteers without lung disease nor congestion (9 non-smokers, 4 exsmokers, 5 smokers). After intravenous bolus injection of 13NH3, twenty serial 5.5-second scans followed by six 30-second scans were performed. Regions of interests were assigned on the ventral, lateral and dorsal part of the right lung and time-activity curves were generated through 26 images. The activity curve demonstrated a biexponential clearance from the lung with fast and slow component. The retention fraction (RF), fractional size of the slow component, was calculated, and the half-times (t 1/2) of both components were also evaluated. A significant increase of RF and prolongation of t 1/2 of slow component were observed in smokers compared to non-smokers and exsmokers. However, no significant difference of RF nor t 1/2 of both components was observed between non-smokers and exsmokers. These results suggest that long term smoking may modify the pulmonary kinetics of 13NH3, but the change is reversible after cessation of smoking for one year or longer.
Adult↗
Reserpine-induced reduction of in vivo binding of SCH 23390 and N-methylspiperone and its reversal by d-amphetamine.
In order to clarify the role of endogenous dopamine in the binding of [3H]SCH23390 and [3H]N-methylspiperone to the mouse striatum in vivo, the effects of reserpine and the reversal of these effects by d-amphetamine were investigated. Radioactivity was measured in the striatum and cerebellum following i.v. injection of each ligand into control and drug-treated mice. The ratio of radioactivity in the striatum to that in the cerebellum, plotted as a function of time, showed a linear correlation. Pretreatment with reserpine 24 h prior to injection of tracer significantly decreased the in vivo binding of both [3H]SCH23390 and [3H]N-methyl-spiperone in a dose-dependent manner. Saturation experiments indicated that these changes in in vivo binding were due mainly to changes in apparent affinity rather than to the number of binding sites available. Administration of d-amphetamine to reserpine-treated mice reversed the effect of reserpine in a dose-dependent manner. Blockade of dopamine D1 receptors with SCH23390 did not prevent the reversal by d-amphetamine of [3H]N-methylspiperone binding in vivo; however, treatment with haloperidol did prevent the effect of d-amphetamine on [3H]SCH23390 binding. These results suggest that dopamine D2 receptor-mediated neurotransmission might itself regulate the binding of dopamine to receptors in vivo.
Animals↗