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Biomedical subjects

T Ido

Publications and source records attributed to T Ido.

At least 55 records · Page 3Linked to original sources

Effects of haloperidol and cocaine pretreatments on brain distribution and kinetics of [11C]methamphetamine in methamphetamine sensitized dog: application of PET to drug pharmacokinetic study.

Repeated administration of methamphetamine (MAP) causes behavioral sensitization in animals. We previously reported that the maximum accumulation level of [11C]MAP in the MAP-sensitized dog brain was 1.4 times higher than that in the control. In behavioral studies, haloperidol (a dopamine D2 receptor antagonist) prevents MAP-induced behavioral sensitization, and cocaine (a dopamine reuptake blocker) has the cross-behavioral sensitization with MAP. In the present study, to elucidate the relation between the MAP-induced behavioral sensitization and the pharmacokinetics of MAP, we investigated the effects of haloperidol and cocaine pretreatments on brain regional distribution and kinetics of [11C]MAP using positron emission tomography (PET). A significant increase of [11C]MAP uptake into the sensitized dog brain was prevented by haloperidol and cocaine pretreatments. These pharmacokinetic changes were not due to the changes in the rate of MAP metabolism. These results suggest haloperidol and cocaine can change the cerebral pharmacokinetic profile of MAP in the behavioral-sensitized dog. The variations of MAP-accumulation may affect the development or expression of MAP-induced behavioral sensitization.

Animals↗

In vivo diagnosis of human malignant melanoma with positron emission tomography using specific melanoma-seeking 18F-DOPA analogue.

Detection and diagnosis of human malignant melanoma by Positron Emission Tomography (PET) using 18F-10B-L-BPA, a specific melanogenesis-seeking compound synthesized for use in Boron Neutron Capture Therapy for malignant melanoma (NCT), has been developed. This resulted in a novel, highly effective methodology for the selective three dimensional imaging of metastatic malignant melanomas, and for accurate determination of 10B concentration in the tumor and surrounding tissue, providing almost all diagnostic information necessary for complete non-invasive radiation dose planning in the treatment of malignant melanoma both for NCT as well as other therapeutic modalities.

Boron↗

Heterogeneity of myocardial fluoro-18 2-deoxyglucose uptake in patients with apical hypertrophic cardiomyopathy.

We have shown that myocardial glucose metabolism is heterogeneous in patients with hypertrophic cardiomyopathy. It is not known, however, whether glucose metabolism is impaired in patients with apical hypertrophic cardiomyopathy, which is fairly common in Japan. We studied 7 patients with apical hypertrophic cardiomyopathy and 5 normal subjects using fluoro-18 2-deoxyglucose (FDG) and positron emission tomography (PET). We calculated regional FDG fractional uptake and the inter-regional coefficient of variation (CV) of FDG fractional uptake in the interventricular septal, anteroapical, and posterolateral regions. The regional FDG fractional uptake was similar in the 2 groups and among the 3 different segments within each group. However, the inter-regional CV of FDG fractional uptake was increased in the anteroapical wall segment of the patient group compared with the control group and also with the other 2 regions in the patient group. The results did not differ when we studied another 5 patients and 6 normal control subjects with a PET scanner with higher spatial resolution. These data suggest that myocardial glucose metabolism may be impaired in the anteroapical wall segment of patients with apical hypertrophic cardiomyopathy.

Adult↗

Myocardial glucose metabolism is different between hypertrophic cardiomyopathy and hypertensive heart disease associated with asymmetrical septal hypertrophy.

Myocardial glucose metabolism has been shown to be heterogeneous in patients with hypertrophic cardiomyopathy (HCM). We tested the hypothesis that myocardial glucose metabolism differs between patients with HCM and those with hypertensive heart disease (HHD) associated with asymmetrical septal hypertrophy. We studied 12 patients with HCM, 7 HHD patients associated with asymmetrical septal hypertrophy using 18F 2-deoxyglucose (FDG) and positron emission tomography. We calculated % FDG fractional uptake in the inter-ventricular septum and posterolateral wall. Heterogeneity of FDG uptake was evaluated by % interregional coefficient of variation of FDG fractional uptake in each wall segment. In both the interventricular septum and posterolateral wall, % FDG fractional uptake was not significantly different between the two groups. The % interregional coefficient of variation for both interventricular septum (10.6 +/- 1.6 vs. 4.1 +/- 0.5, p < 0.01) and posterolateral wall (5.9 +/- 0.7 vs. 3.8 +/- 0.5, p < 0.05) was significantly larger in patients with HCM than in HHD patients associated with asymmetrical septal hypertrophy. Echocardiography demonstrated that the degree of asymmetrical septal hypertrophy was similar between the two groups. These results suggest that myocardial glucose metabolism may be more heterogeneous in patients with HCM compared to HHD patients associated with asymmetrical septal hypertrophy, although the left ventricular shape is similar. The difference in the heterogeneity might have resulted from differences in the pathogeneses of the two diseases.

Adolescent↗

Influence of chemotherapy on FDG uptake by human cancer xenografts in nude mice.

UNLABELLED: This study evaluated the use of PET with 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG) for monitoring chemotherapy effects, using a human cancer xenograft (poorly differentiated human gastric cancer) in vivo model. METHODS: Tumor 18F-FDG uptakes and sizes were measured after administrating mitomycin (MMC), cisplatin (CDDP) and adriamycin (ADR) to xenograft-bearing nude mice and compared with 18F-FDG tumor uptake and tumor size in a non-therapy group. The correlation between the uptake and size was also assessed. RESULTS: The largest reduction in tumor size after chemotherapy occurred in the MMC administered group, followed by the CDDP case, with no reduction in the ADR group as compared to the controls. Fluorine-18-FDG tumor uptake after chemotherapy was also decreased in the MMC and CDDP groups, in that order, but not in the ADR case. With MMC and CDDP, size reduction became significant on Days 8 or 11, whereas 18F-FDG tumor uptake had already been decreased on Days 3 or 7. CONCLUSION: Fluorine-18-FDG uptake decreases in parallel to the efficacy of anticancer agents and correlates with subsequent morphologic changes. We conclude that 18F-FDG PET tumor images are indeed useful for monitoring the effects of cancer chemotherapy.

Adenocarcinoma↗

Stimulated glucose uptake in the ischemic border zone: its dependence on glucose uptake in the normally perfused area.

UNLABELLED: During acute regional myocardial ischemia, a "border zone" exists where the spatial distributions of blood flow and substrate uptake show gradual changes. We investigated the relationship between blood flow and glucose uptake in the border zone during acute regional ischemia. METHODS: Newly developed quantitative autoradiography using imaging plates and two long-lived radioisotopes was applied to rat hearts subjected to 30 min of left coronary artery occlusion. Blood flow, glucose uptake and fatty acid uptake was assessed with 4-[N-methyl-14C]iodoantipyrine, 2-deoxy-D-[1-3H]glucose (3H-DG) and beta-methyl[1-14C]heptadecanoic acid (14C-BMHDA), respectively. RESULTS: In rats showing 3H-DG uptake in the normally perfused area (Norm) of 254 +/- 96 Bq/mg (high-DG) and 56 +/- 20 Bq/mg (low-DG) (n = 4 for each), 3H-DG uptake in the border zone was 148 +/- 52 Bq/mg and 58 +/- 15 Bq/mg (p < 0.05 high- versus low-DG), respectively. The relationship between blood flow and 3H-DG uptake in the border zone was altered by the different 3H-DG uptake levels in Norm. In high-DG, 3H-DG uptake in the border zone was reduced significantly according to the decrease in the percentage of blood flow. However, in low-DG, no significant differences in 3H-DG uptake were found among the regions in the border zone with different levels of the percentage of blood flow, except in the region with 10%-19% of the percentage of blood flow. In the border zone, the percentage of 3H-DG uptake per unit blood flow normalized to that in Norm increased according to the decrease in the percentage of blood flow, and this increase was steeper in low-DG than in high-DG (p < 0.0005). The percentage of 14C-BMHDA uptake was lower than the percentage of 3H-DG uptake (27 +/- 3% versus 78 +/- 18% of that in Norm, p < 0.0005) in the peripheral ischemic area. CONCLUSION: The relationship between blood flow and glucose uptake in the ischemic border zone was altered by the different glucose uptake levels in Norm. Glucose uptake in the border zone was higher in rats with higher glucose uptake levels in Norm, suggesting that glucose uptake in the border zone stimulated by ischemia can be accelerated still more by humoral factors.

Animals↗

[Fluorine-18 labeled 6-fluoro-L-dopa: systematization and evaluation of its usefulness].

6-[18F]Fluoro-L-dopa (L-3,4-dihydroxy-6-[18F]fluorophenylalanine; 6-[18F]FDPA) is useful to assess presynaptic dopamine metabolism in central nervous system. In this paper, we report on the usefulness of the 6-[18F]FDOPA synthesis system developed for the routine synthesis. This system consists of the 6-[18F]FOPA synthesis and the separation units in conjunction with controller using a personal computer. The synthesis time of 6-[18F]FDOPA was 73 minutes. The typical yield and specific activity were 1.4-2.4 GBq and 244-270 MBq/mumol at the end of synthesis, respectively, under the irradiation condition of 50 microA for 130 minutes. The radiochemical yields of 6-[18F]FDOPA were 31.3-38.7% based on the [18F]acetylhypofluorite, and the results were affected with the condition of potassium acetate (AcOK) to produce gaseous [18F]acetylhypofluorite. This system is useful for the routine production of 6-[18F]FDOPA because of its high yield and high specific activity while maintaining AcOK in good condition, and decreasing the radiation exposure for chemist.

Brain↗

Positron emission tomography study of the alterations in brain distribution of [11C]methamphetamine in methamphetamine-sensitized dog.

We newly prepared a MAP-sensitized dog by repeated MAP treatment and studied the brain distribution of [11C]MAP in the normal and the MAP-sensitized dog using PET. The maximal level of accumulation of [11C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. No difference was found in the metabolism of MAP between the two conditions. The significant increase of [11C]MAP in the MAP-sensitized brain indicates that subchronic MAP administration causes some functional change in the uptake site of MAP. The pharmacokinetic change may, in part, account for behavioral sensitization.

Animals↗

Biological evaluation of 5-methyl-branched-chain omega-[18F]fluorofatty acid: a potential myocardial imaging tracer for positron emission tomography.

5-Methyl-17-[18F]fluoroheptadecanoic acid (5-MFHA) has been proposed as a new myocardial imaging tracer for positron emission tomography (PET), containing methyl-branching at the odd-numbered position, except the 3-position. To compare the site of methyl-branching of fatty acids on the contribution to myocardial imaging, the biological evaluation of 5-MFHA-using accumulation studies, metabolic studies, and PET studies of the heart muscle-was investigated. In the comparative biodistribution studies for 16-[18F]fluoropalmitic acid (FPA), 3-methyl-17-[18F]fluoroheptadecanoic acid (3-MFHA) and 5-MFHA, the initial myocardial uptake of 5-MFHA (2.64 [%dose/g tissue]) was relatively high between those of FPA and 3-MFHA (3.45 and 1.58, respectively), and the washout from myocardium of 5-MFHA was midway between those of FPA and 3-MFHA. In the lipid analysis studies, 5-MFHA was mainly metabolized to triglycerides in the myocardium, and its metabolic pattern was similar to that of straight-chain fatty acids (FPA). In the PET studies using 5-MFHA in canines, good myocardial images were obtained for up to 30 min after injection.

Animals↗

Brain 6-[18F]fluorodopa metabolism in early and late onset of Parkinson's disease studied by positron emission tomography.

We measured 6-[18F]fluorodopa (FDOPA) uptake in the caudate nucleus and the putamen of 20 patients with early and late onset of Parkinson's disease (EOPD and LOPD) and 20 normal control subjects using positron emission tomography. The mean influx rate constant values (Ki) were significantly reduced in the caudate nucleus and the putamen of the patients with EOPD and LOPD compared with age-matched control groups (p < 0.01), respectively. There were significant negative correlations between Ki values in the caudate nucleus (r = -0.67, p = 0.0024) and the putamen (r = -0.67, p = 0.0014), and duration of disease in the LOPD group compared with the EOPD group. Similar negative relationships between Ki values and clinical stages by Hoehn and Yahr and degrees of main clinical symptoms (bradykinesia, tremor and rigidity) were more markedly seen in the LOPD group than in the EOPD group. The present results suggest that the function of presynaptic dopaminergic terminals correlates well with clinical disease severity and degrees of main symptoms in the LOPD group, but not in the EOPD group. We speculate that compensatory up-regulatory function in the postsynaptic dopaminergic receptors may modify disease severity and the degrees of main clinical symptoms of EOPD.

Adult↗

PET imaging of primary mediastinal tumours.

Mediastinal masses include a wide variety of tumours and remain an interesting diagnostic challenge for radiologist. We performed positron emission tomography (PET) studies of primary mediastinal tumours in order to predict the malignancy of these tumours preoperatively. Twenty-two patients with primary mediastinal tumours were studied with PET using 2-deoxy-2-[18F]fluoro-D-glucose (FDG). The histological findings of surgical pathology or biopsy, or mediastinoscopy were compared with those of computerised tomography (CT) and PET. PET images were evaluated semiquantitatively using the differential uptake ratio (DUR). Increased FDG uptake was observed in nine of ten patients with malignant tumours, including thymic carcinomas, lymphomas, invasive thymomas and a case of sarcoidosis. A moderate level of FDG uptake was found in a myeloma, non-invasive thymomas, and a schwannoma, whereas a low uptake was observed in a teratoma and various benign cysts. The mean FDG uptake of malignant tumours was significantly higher than that of benign tumours. Both thymic cancer and invasive thymoma showed a high FDG uptake. CT examination resulted in three false-negative and two false-positive cases when used in predicting tumour invasion, while PET was associated with a false-positive and a false-negative case. In conclusion, the use of FDG with PET is clinically helpful in evaluating the malignant nature of primary mediastinal tumours. Our results also suggest that a high FDG uptake reflects the invasiveness of malignant nature of thymic tumours.

Adolescent↗

The independent association of smoking and drinking with serum beta-carotene levels among males in Miyagi, Japan.

BACKGROUND: Previous studies indicated that serum beta-carotene levels were low among smokers and drinkers. However these findings may result from the strong relationship between smoking and drinking. METHODS: Data were collected from 1902 males randomly selected from participants of a cohort study. The effects of smoking on serum beta-carotene levels were assessed according to drinking status (non-drinker, ex-drinker and current drinker), and those of drinking were assessed according to smoking status (ex-smoker and current smoker) using general linear model including other factors (age, intake of green-yellow vegetables, intake of carrot or pumpkin, body mass index serum cholesterol levels.) RESULTS: An inverse dose-response relationship between daily consumption of alcohol and beta-carotene levels was observed regardless of smoking status, and also between number of cigarettes smoked per day and beta-carotene levels regardless of drinking status. CONCLUSION: These results suggest that cigarette smoking and alcohol drinking reduce beta-carotene levels independently.

Adult↗

Analysis of plasma metabolites during human PET-studies with three receptor ligands, [11C]YM-09151-2, [11C]doxepin and [11C]pyrilamine.

Carbon-11 labeled metabolites in human plasma were analyzed by high-performance liquid chromatography during positron emission tomography (PET) studies using the dopamine D2 ligand [11C]YM-09151-2 as well as the histamine H1 ligands [11C]doxepin and [11C]pyrilamine. For all the three tracers, blood clearance of the radioactivity was extremely rapid after an i.v. injection. The plasma protein-binding of [11C]YM-09151-2 and [11C]doxepin had protective effects upon the metabolic alteration of the ligands, whereas [11C]pyrilamine was free from the protein-binding and immediately degraded. The degradation of [11C]doxepin was more rapid in epileptic patients on medication than in normal subjects. These results indicate that analysis of metabolites in the plasma is necessary to determine the accurate arterial input function for quantitative PET measurement.

Adult↗

Feasibility of fluorine-18-fluorophenylalanine for tumor imaging compared with carbon-11-L-methionine.

UNLABELLED: L-[methyl-11C]methionine (11C-Met) is a useful tracer for tumor imaging with PET. The drawbacks include a short half-life and high physiological accumulation in abdominal organs. To overcome these shortfalls, the feasible use of [18F]fluorophenylalanine (18F-Phe), which shares the same amino acid transport system with Met, for tumor imaging was examined. METHODS: The time course of tissue distribution of 18F-Phe and the tumor uptake response to radiotherapy were compared with 14C-Met and [3H] thymidine (3H-Thd) in the rat AH109A tumor model. Intratumoral distribution of 18F-Phe was compared with 14C-Met and 14C-Thd using double-tracer macroautoradiography (ARG). We also evaluated whole-body ARG. RESULTS: Tumor uptake of 18F-Phe peaked at 60 min postinjection and was higher than that of the liver, intestine and kidney but lower than the pancreas. Tumor uptake of 18F-Phe was similar to that of 14C-Met. Tumor-to-blood and tumor-to-muscle ratios were higher in 14C-Met compared with that of 18F-Phe because of the rapid blood clearance of 14C-Met. With whole-body ARG, the tumor was clearly visualized with high contrast. Radiotherapeutic response of tumor uptake of 18F-Phe was as rapid as that with 14C-Met and with 3H-Thd. Intratumoral distribution of 18F-Phe and 14C-Met were identical, and 18F-Phe and 14C-Thd were similar. CONCLUSION: Fluorine-18-Phe seems to be a potentially useful amino acid tracer for tumor imaging with a longer half-life than 11C, with higher tumor contrast in the abdomen than Met and a similar sensitive response to radiotherapy.

Animals↗

[Development of simple on-line [oxygen-15]water infuser].

A [15O]water production and infusion system was newly developed for blood flow study with positron emission tomography. The system utilizes a electrostatic cooling unit to liquify [15O]vapor in a coiled plastic tube. Labeled [15O]water is collected into an infusion syringe by a wash of the trapping tube with saline. The system is simple and efficient; the recovery rate of [15O]water is over 90% at 10 degrees C of cooling temperature.

Cerebrovascular Circulation↗

The effects of the beta-adrenergic-blocking agents, timolol and carteolol, on plasma lipids and lipoproteins in Japanese glaucoma patients.

PURPOSE: To determine whether two topical beta-blockers, timolol and carteolol, differently affect plasma lipids and lipoproteins in normolipidemic Japanese patients with glaucoma. PATIENTS AND METHODS: Thirty-three normolipidemic patients with primary open-angle glaucoma or ocular hypertension were randomly allocated to and completed 16 weeks of bilateral treatment with 0.5% timolol, 1.0% carteolol, or 2.0% carteolol twice daily in a three-center, prospective study. Patients using any drugs affecting plasma lipids or with a history of beta-blocker use of hyperlipoproteinemia were excluded. Fasting blood lipids and lipoproteins, including total cholesterol, high-density lipoprotein cholesterol, triglyceride, and apoproteins, were measured three times before therapy was initiated. These measurements were repeated every 4 weeks during the treatment period. RESULTS: The level of high-density lipoprotein cholesterol significantly decreased in the timolol treatment group but did not change in the carteolol treatment groups. The ratio of total cholesterol minus high-density lipoprotein cholesterol to high-density lipoprotein cholesterol increased in the timolol treatment group. CONCLUSIONS: Topical beta-blockers do affect plasma lipids in Japanese patients with glaucoma. The effects of timolol are greater than those of carteolol.

Adrenergic beta-Antagonists↗

[Regional distribution of the muscarinic cholinergic receptor in the human brain studied with 11C-benztropine and PET using an anatomical standardization technique].

We measured regional distribution of the muscarinic cholinergic receptor in the normal human brain with 11C-benztropine (BZT) and positron emission tomography (PET) using an anatomical standardization technique. Seven normal volunteers who gave informed consents were involved in this study. Immediately after intravenous injection of 11C-BZT into the subjects, we started dynamic PET scanning and serial frequent arterial blood sampling. Analyses of plasma metabolites were also performed at selected time points and plasma time activity curves (TAC) of unmetabolized ligand were generated. From these PET and TAC data, we obtained Patlak plot slope calculation images. Using the HBA (human brain atlas) system, the Patlak plot slope calculation image of each subject was transformed into the shape of the standard brain. Mean and standard deviation (SD) calculation images were generated from those anatomically standardized images. On these mean and SD images, we placed regions of interest which were previously outlined on a MR image of the standard brain. From those data, we found the highest receptor distribution in the striatum and occipital cortex, as well as high distribution in the frontal, parietal, and temporal cortices, which were consistent with previous reports. These results suggested that anatomical standardization of PET receptor images with 11C-BZT will be useful for delineating the physiological or pathological alterations of the muscarinic cholinergic receptor in the human brain.

Adolescent↗