High occupancy of sigma1 receptors in the human brain after single oral administration of donepezil: a positron emission tomography study using [11C]SA4503.

The acetylcholinesterase (AChE) inhibitor donepezil is also a sigma1 receptor agonist. We examined whether donepezil binds to sigma1 receptors in the living human brain after a single oral administration. Dynamic positron emission tomography (PET) data acquisition using the selective sigma1 receptor ligand [11C]SA4503 was performed to evaluate quantitatively the binding of [11C]SA4503 to sigma1 receptors in eight healthy male volunteers.

A statistical clustering approach to visualizing the relationship between early and delayed images in whole-body FDG-PET.

We propose a new method for diagnostic assistance in oncology, [fluorine-18]-2-fluoro-2-deoxy-D: -glucose (FDG)-positron emission tomography (PET). Early and delayed scans were performed on 10 patients with lung cancer by use of an ECAT EXACT 47 PET scanner, and standardized-uptake-value (SUV) images were created. Three segmentation (S1, S2, and S3) maps were created from the early and delayed SUV images according to various thresholds (SUV(threshold) = 2.

Expanding the clinical phenotype of SNCA duplication carriers.

SNCA duplication is a recognized cause of familial Parkinson's disease (PD). We aimed to explore the genetic and clinical variability in the disease manifestation. Molecular characterization was performed using real-time PCR, SNP arrays, and haplotype analysis.

Evaluation of individual skeletal muscle activity by glucose uptake during pedaling exercise at different workloads using positron emission tomography.

Skeletal muscle glucose uptake closely reflects muscle activity at exercise intensity levels <55% of maximal oxygen consumption (VO2max). Our purpose was to evaluate individual skeletal muscle activity from glucose uptake in humans during pedaling exercise at different workloads by using [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET). Twenty healthy male subjects were divided into two groups (7 exercise subjects and 13 control subjects).

PET pharmacokinetic analysis to estimate boron concentration in tumor and brain as a guide to plan BNCT for malignant cerebral glioma.

Introduction: To plan the optimal BNCT for patients with malignant cerebral glioma, estimation of the ratio of boron concentration in tumor tissue against that in the surrounding normal brain (T/N ratio of boron) is important. We report a positron emission tomography (PET) imaging method to estimate T/N ratio of tissue boron concentration based on pharmacokinetic analysis of amino acid probes.

Methods: Twelve patients with cerebral malignant glioma underwent 60 min dynamic PET scanning of brain after bolus injection of (18)F-borono-phenyl-alanine (FBPA) with timed arterial blood sampling.

Preclinical and the first clinical studies on [11C]CHIBA-1001 for mapping alpha7 nicotinic receptors by positron emission tomography.

Objective: 4-[(11)C]methylphenyl 2,5-diazabicyclo[3.2.2]nonane-2-carboxylate ([(11)C]CHIBA-1001), a 4-methyl-substituted derivative of the selective alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) partial agonist 4-bromophenyl 1,4 diazabicyclo[3.

Clinical significance of UDP-glucuronosyltransferase 1A1*6 for toxicities of combination chemotherapy with irinotecan and cisplatin in gynecologic cancers: a prospective multi-institutional study.

Background: To investigate the effects of UDP-glucuronosyltransferase 1A1 (UGT1A1) *28, *6 and *27 in patients with gynecologic cancer who received chemotherapy with irinotecan and cisplatin.

Methods: Patients eligible for this study had cervical or ovarian cancer treated with chemotherapy; a course of the regimen consisted of 60 mg/m(2) of irinotecan on days 1, 8 and 15, and 60 mg/m(2) of cisplatin on day 1 every 4 weeks. UGT1A1 polymorphisms and toxicities were analyzed.

Adenosine A(1) receptors using 8-dicyclopropylmethyl-1-[(11)C]methyl-3-propylxanthine PET in Alzheimer's disease.

Objective: Adenosine is an endogenous modulator of synaptic functions in the central nervous system. The effects of adenosine are mediated by at least four adenosine receptor subtypes. Decreased density of adenosine A1 receptors, which is a major subtype adenosine receptor in the hippocampus, has been reported in vitro in Alzheimer's disease.

Regional analysis of age-related decline in dopamine transporters and dopamine D2-like receptors in human striatum.

Unlabelled: The purpose of this study was to evaluate the mechanisms of age-related decline of dopamine transporter (DAT) and dopamine D(2)-like receptor (D2R) densities in the human striatum by focusing on regional difference.

Methods: Positron emission tomography (PET) with [(11)C]CFT and [(11)C]raclopride for measuring DATs and D2Rs, respectively, was performed on 16 healthy volunteers ranging from 21 to 74 years in age. To evaluate in detail the regional difference within the striatum, in addition to the conventional region-of-interest-based analysis, we created a parametric image that enabled us to visualize the regional decline rate on a voxel-by-voxel basis, mapping the slope of the regression line between the age and uptake index of each tracer.

Contributions of biological tumor parameters to the incorporation rate of L: -[methyl-(11)C] methionine into astrocytomas and oligodendrogliomas.

We compared the tumor uptake of (11)C-methionine (MET) with positron emission tomography (PET) with the results of a pathological analysis to examine the proliferative potential and microvessel density measured with immunostaining for MIB-1 and factor VIII, respectively, from 33 patients with glioma. The MET uptake in oligodendrogliomas was significantly greater than that in grade 2 astrocytomas and comparable to those in grade 3 and 4 astrocytomas. The MIB-1 index of oligodendroglioma meanwhile was comparable to that of grade 2 astrocytoma.

Neuroradiologic evidence of pre-synaptic and post-synaptic nigrostriatal dopaminergic dysfunction in idiopathic Basal Ganglia calcification: a case report.

Idiopathic basal ganglia calcification (IBGC) is a neuropathological condition known to manifest as motor disturbance, cognitive impairment, and psychiatric symptoms. The pathophysiology of the psychiatric symptoms of IBGC, however, remains controversial. A previous biochemical study suggested that dopaminergic impairment is involved in IBGC.

Glioma surgery using a multimodal navigation system with integrated metabolic images.

Object: A multimodal neuronavigation system using metabolic images with PET and anatomical images from MR images is described here for glioma surgery. The efficacy of the multimodal neuronavigation system was evaluated by comparing the results with that of the conventional navigation system, which routinely uses anatomical images from MR and CT imaging as guides.

Methods: Thirty-three patients with cerebral glioma underwent 36 operations with the aid of either a multimodal or conventional navigation system.

Purification of L-glutamate decarboxylase from monkey brain.

Glutamate decarboxylase (GAD) is an enzyme that synthesizes gamma-aminobutyrate (GABA), a major inhibitory neurotransmitter in the central nervous system. Post-translational modification of GAD, such as N-terminal blockage, phosphorylation-dephosphorylation, and palmitoylation, is an important factor in the biological activity of GAD. In order to address the significance of post-translational events on GAD, we thought it crucial to obtain a non-recombinant form of GAD.

Autologous serum eardrops therapy with a chitin membrane for closing tympanic membrane perforations.

Objective: Office treatment for chronic tympanic membrane (TM) perforations has limitations, and alternative methods to myringoplasty are sometimes needed. Serum lacks antigenicity and contains a large variety of growth factors known to modulate proliferation of various tissues to promote wound healing effects. Our purpose was to evaluate the feasibility of autologous serum eardrops therapy with a chitin membrane for closing TM perforations.

Voxel- and ROI-based statistical analyses of PET parameters for guidance in the surgical treatment of intractable mesial temporal lobe epilepsy.

Objective: Positron emission tomography (PET) can be used to locate epileptic foci in patients with mesial temporal lobe epilepsy (MTLE) by measuring multiple parameters of the brain. We investigated a series of patients with MTLE using PET measurements of three parameters: the cerebral blood flow measured with [15 O] H2O, the uptake of [18F] fluorodeoxyglucose (FDG), an index of the cerebral metabolism rate of glucose, and the distribution volume (DV) of [11C] flumazenil (FMZ), an index of the binding potential of central benzodiazepine receptor. We compared predictive values obtained from two methods: a voxel-based statistical analysis using statistical parametric mapping (SPM) and an asymmetry index obtained by placing regions of interest (ROIs) on PET images.

Successive positron emission tomography measurement of cerebral blood flow and neuroreceptors in the human brain: an 11C-SA4503 study.

For evaluating a newly developed radioligand for positron emission tomography (PET), successive measurements of regional cerebral blood flow (rCBF) and the kinetics of the radioligand in the same subject are preferable in the first clinical trial. In this study, we demonstrate an example for the study of (11)C-labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylprophyl) piperazine ((11)C-SA4503) for mapping sigma(1) receptors in the human brain. Five healthy male subjects underwent two successive PET scans with (15)O-H(2)O to measure the rCBF and with (11)C-SA4503 (dynamic 60-min scan).

Influence of mild hyperglycemia on cerebral FDG distribution patterns calculated by statistical parametric mapping.

Objective: In clinical cerebral 2-[(18)F]fluoro-2-deoxy-D: -glucose positron emission tomography (FDG-PET) studies, we sometimes encounter hyperglycemic patients with diabetes mellitus or patients who have not adhered to the fasting requirement. The objective of this study was to investigate the influence of mild hyperglycemia (plasma glucose range 110-160 mg/dl) on the cerebral FDG distribution patterns calculated by statistical parametric mapping (SPM).

Methods: We studied 19 healthy subjects (mean age 66.

Low density of sigma1 receptors in early Alzheimer's disease.

Objective: The sigma(1) receptor is considered to be involved in cognitive function. A postmortem study reported that the sigma(1) receptors were reduced in the hippocampus in Alzheimer's disease (AD). However, in vivo imaging of sigma(1) receptors in the brain of AD patients has not been reported.

Shortened protocol in practical [11C]SA4503-PET studies for sigma1 receptor quantification.

In practical positron emission tomography (PET) diagnosis, a shortened protocol is preferred for patients with brain disorders. In this study, the applicability of a shortened protocol as an alternative to the 90-min PET scan with [(11)C]SA4503 for quantitative sigma(1) receptor measurement was investigated. Tissue time-activity curves of 288 regions of interest in the brain from 32 [(11)C]SA4503-PET scans of 16 healthy subjects prior to and following administration of a selective serotonin reuptake inhibitor (fluvoxamine or paroxetine) were applied to two algorithms of quantitative analysis; binding potential (BP) was derived from compartmental analysis based on nonlinear estimation, and total distribution volume (tDV) was derived from Logan plot analysis.

[Amyloid imaging].

Amyloid imaging has recently emerged as a non-invasive neuroimaging technique to visualize the accumulation of amyloid-beta in living brain. Several modalities such as PET, SPECT, MRI, and optical imaging has been adopted for this purpose, the nuclear medicine technique of PET firstly put it to practical use because of its high sensitivity. Among many radioligand tracers proposed, Pittsburgh Compound-B (PIB) has successfully spread over the world as a standard amyloid imaging probe.

[Adenosine receptor--relation to dopaminergic system].

Adenosine is produced by conversion of intra- and extracellular adenine nucleotides, and plays a role as an endogenous modulator of synaptic functions in the central nervous system. The adenosine A2A receptors (A2AR) are enriched in dopamine-rich areas of the brain, such as the basal ganglia, and are thought to interact with dopamine D2 receptor (D2R) negatively. Selective A2AR antagonists have attracted attention as the treatment of Parkinson's disease (PD).

Robust estimation of the arterial input function for Logan plots using an intersectional searching algorithm and clustering in positron emission tomography for neuroreceptor imaging.

The Logan plot is a powerful algorithm used to generate binding-potential images from dynamic positron emission tomography (PET) images in neuroreceptor studies. However, it requires arterial blood sampling and metabolite correction to provide an input function, and clinically it is preferable that this need for arterial blood sampling be obviated. Estimation of the input function with metabolite correction using an intersectional searching algorithm (ISA) has been proposed.

Measurement of the 11C-flumazenil binding in the visual cortex predicts the prognosis of hemianopia.

In order to determine whether functional neuroimaging studies can predict the prognosis of hemianopia due to organic cerebral disorders, we studied 8 patients (6 men and 2 women; age, 56.0+/-8.6 years) with homonymous hemianopia and compared them with 15 normal subjects (6 men and 9 women; age, 54.

Presynaptic and postsynaptic nigrostriatal dopaminergic functions in multiple system atrophy.

A simultaneous evaluation of presynaptic and postsynaptic dopaminergic positron emission tomography markers, the dopamine transporters and the dopamine D2-like receptors, was performed in eight patients with parkinsonian phenotype of multiple system atrophy. Both presynaptic and postsynaptic markers were revealed to have declined in such a manner that they kept strong positive correlation throughout the striatum of all patients, suggesting that the degeneration process in the striatum may involve the entire structure of the dopaminergic synapse. In two L-3,4,dihydroxyphenyl-alanine-responsive cases, the balance of decline in two markers was relatively shifted to presynaptic dominant side.

Distribution volume as an alternative to the binding potential for sigma1 receptor imaging.

The applicability of total distribution volume (DV(t)) as an alternative to binding potential (BP) was investigated for neuroreceptor mapping by positron emission tomography (PET). BP is defined as a representative quantity of receptor density. However, for making parametric images of BP, a reference region where an aimed receptor has a very low density is assumed to exist in a target region such as the brain.