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Kentaro Hatano

Publications and source records attributed to Kentaro Hatano.

14 recordsLinked to original sources
PubMed2006

PET tracers for imaging of the dopaminergic system.

The dopaminergic system plays a major role in neurological and psychiatric disorders such as Parkinson's disease, Huntington's disease, tardive dyskinea and schizophrenia. Knowledge on altered dopamine synthesis, receptor densities and status are important for understanding the mechanisms underlying the pathogenesis and therapy of diseases. PET provides a non-invasive tool to investigate these features in vivo, provided the availability of suitable radiopharmaceuticals. To investigate presynaptic function, PET-tracers have been developed to measure dopamine synthesis and transport. For the former the most commonly used tracers are 6-[(18)F]FDOPA and 6-[(18)F]FMT, whereas for the latter several (11)C/(18)F-labeled tropane analogues are being clinically used. Postsynaptically, dopamine exerts actions through several subtypes of the dopamine receptor. The dopamine receptor family consists of 5 subtypes D(1)-D(5). In order to investigate the role of each receptor subtype, selective and high-affinity PET-radioligands are required. For the dopamine D(1)-subtype the most commonly used ligand is [(11)C]SCH 23390 or [(11)C]NNC 112, whereas for the D(2)/D(3)-subtype [(11)C]raclopride is a common tracer. [(18)F]Fallypride is a suitable PET-tracer for the investigation of extrapyramidal D(2)-receptors. For the other subtypes no suitable radioligands have been developed yet. This paper gives an overview of the current status on dopamine PET-tracers and the development of new lead compounds as potential PET-tracers by medicinal chemistry.

Animals↗
PubMed2006

[Guideline for the treatment of Hansen's disease in Japan (Second edition)].

ad hoc committee of Japanese Leprosy Association recommends revised standard treatment protocol of leprosy in Japan, which is a modification of World Health Organization's multidrug therapy (WHO/MDT, 1997). For paucibacillary (PB) leprosy, 6 months treatment by rifampicin and dapsone (MDT/PB) is enough. However, for high bacterial load multibacillary (MB) leprosy, 12 months treatment seems insufficient. Thus, (A) For MB with bacterial index (BI) > or = 3 before treatment, 2 years treatment by rifampicin, dapsone and clofazimine (MDT/MB) is necessary. When BI become negative and active lesion is lost within 2 years, no maintenance therapy is necessary. When BI is still positive, one year of MDT/MB is added (3 years in total), followed by maintenance therapy by dapsone and clofazimine until BI negativity and loss of active lesions. (B) For MB with BI < 3 or fresh MB (less than 6 months after the onset of the disease) with BI > or = 3, 1 year treatment by MDT/MB is necessary. When BI become negative and active lesion is lost within one year, no maintenance therapy is necessary. When BI is still positive or active lesion is remaining, additional therapy with MDT/MB for one more year is recommended. This is a simplification of first version in 2000. Brief summary of diagnosis, purpose of therapy, character of drugs, and prevention of deformity is also described.

Clofazimine↗
PubMed2006

Application of 18F-FDG PET for monitoring the therapeutic effect of antiinflammatory drugs on stabilization of vulnerable atherosclerotic plaques.

UNLABELLED: The rupture of atherosclerotic vulnerable plaques and subsequent formation of thrombi are the main factors responsible for myocardial and cerebral infarctions. Because macrophage infiltration plays an essential role in plaque rupturing, pharmacologic therapy that reduces macrophage infiltration is required to stabilize the vulnerable plaques. The monitoring of therapeutic effect is important in assessing the therapeutic effects of drugs for individual patients. We previously reported that (18)F-FDG accumulates in macrophage-rich plaques. The present study was undertaken to investigate the usefulness of (18)F-FDG PET for monitoring therapies that target vascular inflammation. METHODS: Myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits were used in this study. The antioxidant probucol was included in the diet fed to 4 rabbits starting at 10 mo of age (probucol group). In a control study, 4 rabbits received standard rabbit chow (control group). (18)F-FDG PET experiments were performed on both groups before the study and at 1, 3, and 6 mo after treatment. After the last imaging session, the rabbits were sacrificed at 3 h after injection of (18)F-FDG, and the aortas were removed. The accumulated radioactivity was then measured, and the number of macrophages was determined by examination of stained sections. RESULTS: At the age of 10 mo, before the treatment, the aorta could be imaged by (18)F-FDG PET in all rabbits. The aorta could not be imaged after 6 mo of probucol treatment, whereas intense radioactivity was observed in the control rabbits throughout the investigation. The standardized uptake values (SUVs) of the aorta were decreased significantly in the probucol group after 3 mo of intervention as compared with the pretreatment period. The SUVs of the control group were increased gradually at 6 mo. Radioactivity in the aorta was significantly lower in the probucol group than that in the control group. Macrophages were already present at the beginning of the study, and probucol treatment for 6 mo resulted in a significant reduction of macrophage infiltration. CONCLUSION: (18)F-FDG PET was able to image the reduction of inflammation by probucol. (18)F-FDG PET should be useful for evaluating the therapeutic effect of drugs clinically and for the development of new drugs that can stabilize vulnerable plaques. (18)F-FDG PET should be useful for evaluating the therapeutic effect of drugs clinically and for the development of new drugs that can reduce inflammation of vulnerable plaques.

Animals↗
PubMed2004

Rat-PET study without anesthesia: anesthetics modify the dopamine D1 receptor binding in rat brain.

Positron emission tomography (PET) measurements in 6-month-old F344/N rats were performed in the conscious state and the influence of chloral hydrate, ketamine, and pentobarbital anesthesia on dopamine D(1) (DA-D(1)) receptor binding was evaluated using [(11)C]SCH23390, a selective DA-D(1) receptor ligand. To perform the PET study in conscious rats, an original fixation apparatus was developed and the animals were trained to acclimate to the scanning atmosphere for 3 h. This training was carried out twice a day for 2 weeks. PET measurements in conscious rats were successful, since the trained rats scarcely moved during the scanning (as monitored by video camera) and since highly reproducible measurements of binding potential (BP) were derived from their scanning. Chloral hydrate and ketamine anesthesia significantly increased the striatal BP of DA-D(1) receptors by 36% and 46%, respectively, compared to that observed in the conscious state. In contrast, pentobarbital markedly decreased the BP by 41%. These BP values of DA-D(1) receptors were calculated using a curve-fitting method. Our results indicate that PET studies in rats should be performed in the conscious state since the anesthetics dramatically modified ligand-receptor bindings, such as DA-D(1) receptor binding, in rat brain.

Anesthesia↗
PubMed2004

Cognitive- and motor-related regions in Parkinson's disease: FDOPA and FDG PET studies.

OBJECTIVE: Using 6-[(18)F]fluoro-L-dopa (FDOPA) and [(18)F]fluorodeoxyglucoce (FDG) positron emission tomography (PET), multiple regression analyses were performed to determine the specific brain regions that are related to cognitive and motor symptoms in nondemented patients with Parkinson's disease. METHODS: Spatially normalized images of FDOPA influx rate constant (Ki) values and relative regional cerebral metabolic rates for glucose (rrCMRglc) were created. Raven's Coloured Progressive Matrices (RCPM) scores and the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were used to determine the patients' cognitive and motor functions, respectively. Multiple correlation analyses between the FDOPA and FDG images and the cognitive and motor scores were performed for each voxel. RESULTS: RCPM score was significantly positively correlated with the FDOPA Ki in the left hippocampus and with the rrCMRglc in the left middle frontal gyrus and right retrosplenial cortex. Motor function was significantly positively correlated with the FDOPA Ki in the bilateral striatum and with the rrCMRglc in association areas and primary visual cortex. The level of motor function was significantly inversely correlated with the FDOPA Ki in the anterior cingulate gyrus and with the rrCMRglc in bilateral primary motor cortex and right putamen. CONCLUSIONS: Changes of striatal FDOPA uptake and rrCMRglc in the primary motor cortex likely represent dysfunction in the motor system involving the corticobasal ganglia-thalamocortical loop. Change of FDOPA uptake in the anterior cingulate gyrus may be related to up-regulation of dopamine synthesis in surviving dopamine neurons. The regions where correlation with cognitive function was observed belong to a cognitive frontoparietal-hippocampal network.

Biological Transport↗
PubMed2004

Axonal spherical bodies in the peripheral nerves of leprosy patients.

Spherical bodies, roughly 10 micro m in diameter, which have not been reported before, were found in the peripheral nerve axons of specimens collected during post-mortem examination of leprosy patients. These bodies were found in the fascicles of all peripheral nerves of the extremities examined (median, radial, ulnar, peroneal and sciatic nerves). Their incidence was not related to the type of leprosy. The area immediately below the thickened perineurium, a feature associated with leprosy, often showed a large number of spherical bodies. When observed under a transmission electron microscope, the spherical lesions often showed a lamellar structure, although some of them were amorphous. No structure resembling organelles was seen within the bodies. Observation with the merge technique showed a clearly lamellar structure in most of the spherical bodies. These bodies and the surrounding myelin sheaths were partially polarized. The axonal spherical bodies observed in our study seem to represent lesions gradually formed due to glycoprotein denaturation over long periods of time and to be associated with leprosy-caused thickening of the perineurium of peripheral nerves.

Aged↗
PubMed2003

Synthesis and evaluation of 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-[11C]ethyl-1,3-dihydro-2H-benzimidazol-2-one as a brain ORL1 receptor imaging agent for positron emission tomography.

1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-[(11)C]ethyl-1,3-dihydro-2H-benzimidazol-2-one ([(11)C]CPEB) was synthesized by [(11)C]N-ethylation and evaluated as a potential brain ORL1 receptor imaging agent by positron emission tomography. The uptake of [(11)C]CPEB in the mouse brain was 1.9% dose/g, 2 min post-injection, and gradually decreased with time. Receptor-specific binding was observed, however, the contribution of other receptors was observed and the non-specific binding of [(11)C]CPEB was too high for imaging receptors in vivo. Therefore, [(11)C]CPEB is not a suitable tracer for in vivo ORL1 receptor imaging.

Animals↗
PubMed2003

Direct electrophilic radiofluorination of a cyclic RGD peptide for in vivo alpha(v)beta3 integrin related tumor imaging.

The association of the alpha(v)beta(3) integrin with tumor metastasis and tumor related angiogenesis has been suggested. Therefore, by imaging the alpha(v)beta(3) receptor with PET, information concerning the tumor status could be obtained. Cyclic peptides including the RGD sequence, were radiolabeled by direct electrophilic fluorination with [(18)F]AcOF. In tumor-bearing mice, the labeled peptides accumulated at the tumor with a high tumor to blood ratio. These findings suggest that an assessment of tumor characteristics may be obtained by using these (18)F-labeled peptides.

Acetates↗
PubMed2002

Direction of cross-modal information transfer affects human brain activation: a PET study.

The purpose of this study was to determine the functional organization of the human brain involved in cross-modal discrimination between tactile and visual information. Regional cerebral blood flow was measured by positron emission tomography in nine right-handed volunteers during four discrimination tasks; tactile-tactile (TT), tactile-visual (TV), visual-tactile (VT), and visual-visual (VV). The subjects were asked either to look at digital cylinders of different diameters or to grasp the digital cylinders with the thumb and index finger of the right hand using haptic interfaces. Compared with the motor control task in which the subjects looked at and grasped cylinders of the same diameter, the right lateral prefrontal cortex and the right inferior parietal lobule were activated in all the four discrimination tasks. In addition, the dorsal premotor cortex, the ventral premotor cortex, and the inferior temporal cortex of the right hemisphere were activated during VT but not during TV. Our results suggest that the human brain mechanisms underlying cross-modal discrimination have two different pathways depending on the temporal order in which stimuli are presented.

Adult↗
PubMed2002

Striatal and extrastriatal dysfunction in Parkinson's disease with dementia: a 6-[18F]fluoro-L-dopa PET study.

We investigated the relative differences in dopaminergic function through the whole brain in patients with Parkinson's disease without dementia (PD) and with dementia (PDD) using 6-[18F]fluoro-L-dopa (18F-dopa) PET and a voxel-by-voxel analysis. The 10 PD and 10 PDD patients were equivalently disabled, having mean scores of 3.2 +/- 0.6 and 3.2 +/- 0.7, respectively, on the Hoehn and Yahr rating scale. 18F-dopa influx constant (Ki) images of those patients and 15 normal age-matched subjects were transformed into standard stereotactic space. The significant differences between the groups (expressed in mean regional Ki values) were localized with statistical parametric mapping (SPM) on a voxel-by-voxel basis. Compared with the normal group, SPM localized declines of the 18F-dopa Ki bilaterally in the putamen, the right caudate nucleus and the left ventral midbrain for the PD group (P < 0.01, corrected). Compared with the normal group, the PDD group showed reduced 18F-dopa Ki bilaterally in the striatum, midbrain and anterior cingulate area (P < 0.01, corrected). A relative difference in 18F-dopa uptake between PD and PDD was the bilateral decline in the anterior cingulate area and ventral striatum and in the right caudate nucleus in the PDD group (P < 0.001, corrected). Accordingly, we conclude that dementia in PD is associated with impaired mesolimbic and caudate dopaminergic function.

Aged↗
PubMed2002

[Leprosy Control and Basic Health Services Project].

Many tropical and subtropical communicable diseases are prevalent in Myanmar still now. Leprosy also is not completely controlled in spite of making exertions by the Government of Myanmar and more than 10,000 new leprosy patients were detected every year. In response to the pressure of World Health Organization (WHO), the government of Myanmar declared to eliminate this disease by the end of 2003, and all vertical staff concerned with leprosy control program concentrate to reach the goal of elimination (Prevalence rate: less than 1.0 per 10,000 population). Leprosy Control and Basic Health Services Project will be carried out in the project sites for 5 years, that is, from April, 2000 to March, 2001. Project purpose that was mentioned in the PDM were to support the leprosy control programme in Myanmar through the strengthening of Basic Health Service system by conducting training activities and other diseases' control programmes such as TB and Measles, by fully utilizing the above training opportunities. The Project started to conduct the main activities from 2001 as follows, 1. BHS training 2. Training of microscopic diagnosis 3. Sewing training as one of social rehabilitations 4. Training of reconstructive surgery 5. Survey on disabilities of leprosy patients, etc.

Communicable Disease Control↗
PubMed2002

[What is possible for us to corroborate developing countries in the leprosy field?].

Developing countries have their own unique characteristics, histories, and situation. There are great differences from country to country. From the experiences worked in both Bangladesh and Myanmar which share their border, some similarities and dissimilarities among these two greatly different countries are discussed. Considering this, common problems on leprosy in the developing countries are analyzed. The needs of developing countries in the field of leprosy are studied, and the possible way of corroboration for us, Japanese leprosy workers, are suggested.

Developing Countries↗
PubMedDate not supplied

New insight into the analysis of 6-[18F]fluoro-L-DOPA PET dynamic data in brain tissue without an irreversible compartment: comparative study of the Patlak and Logan analyses.

The objective of this study was to show that the Logan analysis is theoretically more appropriate than the Patlak analysis for the assessment of 6-[18F] fluoro-L-DOPA (FDOPA) positron emission tomography (PET) dynamic data in brain tissue without an irreversible compartment, e.g., occipital cortex. Another purpose was to provide the first application of this analysis to real data. Ten normal controls (NC), 10 Parkinson's disease (PD) patients, and 10 Parkinson's disease with dementia (PDD) patients underwent FDOPA PET. The Logan analysis and the Patlak analysis were applied to the occipital cortex with the cerebellum as a reference tissue. In the occipital cortex, the Logan analysis showed a significant difference (p=0.018) between NC and PDD patients. However, the Patlak analysis showed no significant differences, but larger variances. The Logan analysis of FDOPA PET dynamic data in the occipital cortex was considered to be theoretically appropriate and to provide new insight into the analysis of that region.

Aged↗