Research Interests:
[10B]Boronophenylalanine (10B-BPA) has been used as a tumor selective boron carrier for boron neutron capture therapy (BNCT) in the treatment of malignant melanoma1. In the same way, it is thought to be a potential boron carrier for the... more
[10B]Boronophenylalanine (10B-BPA) has been used as a tumor selective boron carrier for boron neutron capture therapy (BNCT) in the treatment of malignant melanoma1. In the same way, it is thought to be a potential boron carrier for the treatment of malignant glioma2–4. Glioma infiltrates peripheral brain tissue and we always fall into the dilemma between resection and preservation of the infiltrated brain. Thus the treatment will be effective in these infiltrative tumors. In our studies of malignant glioma using positron emission tomography (PET), accumulation of 10B-BPA analog, [18F]fluoroboronophenylalanine (18F-10B-FBPA), in tumor lesion was dramatically revealed3. The metabolic analysis of this positron-emitting analog demonstrated that enhancement of the amino acid transport is a primary factor for the high accumulation3,5. [18F]Fluoroboronophenylalanine has been recognized as a compound that is incorporated into tumor cell selectively.
Research Interests:
Research Interests:
Research Interests:
Changes in cerebral hemodynamics due to reconstructive cerebral vascular surgery were evaluated using positron emission tomography (PET). Three minor stroke cases and 1 TIA case, brought on by main trunk stenosis, were included. STA-MCA... more
Changes in cerebral hemodynamics due to reconstructive cerebral vascular surgery were evaluated using positron emission tomography (PET). Three minor stroke cases and 1 TIA case, brought on by main trunk stenosis, were included. STA-MCA anastomoses was performed in two of the cases and carotid endarterectomy was performed in the remaining two cases. CBF, CBV, OEF, CMRO2 and CBF/CBV were investigated using PET with the ROIs fixed in both normal and stenosis areas. On the two cases of STA - MCA anastomosis, clear hemodynamic improvement was not demonstrated. On the two carotid endarterectomy cases, the hemodynamic factors showed improvement.
Research Interests:
Research Interests:
Research Interests:
To elucidate the synaptic transmission in the neural system, we have been developing fundamental studies for intracellular signaling. For clinical application of carbon-11 labeled diacylglycerol (1-[1-11C]butyryl-2-palmitoyl-rac-glycerol:... more
To elucidate the synaptic transmission in the neural system, we have been developing fundamental studies for intracellular signaling. For clinical application of carbon-11 labeled diacylglycerol (1-[1-11C]butyryl-2-palmitoyl-rac-glycerol: 11C-DAG) using positron emission computed tomography (PET), we evaluated the quality and the safety of 11C-DAG as the solution for injection. As a result, 11C-DAG was synthesized within 50 minutes, including the preparation step for injection. The half life time and energy spectrum of 11C-DAG were the same as the physical character of carbon-11, and other radioisotopes were not detected. In the quality control, 11C-DAG solution was negative in the examination of bacterial contamination and the pyrogen test in three successive synthesis procedures. In the acute toxicity test by administration of 11C-DAG and 100 mumol/kg of non-radioactive DAG to the rat intravenously, the systemic condition of the rat was not changed and no abnormalities were found ...
Research Interests:
To evaluate the effects of hemodilution on cerebral hemodynamics and oxygen metabolism in the normal human brain, we measured regional cerebral blood flow, oxygen extraction fraction, oxygen metabolic rate, and regional cerebral blood... more
To evaluate the effects of hemodilution on cerebral hemodynamics and oxygen metabolism in the normal human brain, we measured regional cerebral blood flow, oxygen extraction fraction, oxygen metabolic rate, and regional cerebral blood volume in eight normal volunteers before and after hemodilution using positron emission tomography and oxygen-15-labeled gas inhalation technique. Hemodilution was accomplished by phlebotomy of 400 ml and drip infusion of 500 ml low molecular weight dextran, which reduced hematocrit from 42.5% to 37.2% and arterial oxygen content from 19.1 to 16.9 ml/dl (both p less than 0.005). It also increased mean cerebral blood flow from 45.2 to 47.7 ml/100 ml/min (p less than 0.025), but decreased tissue oxygen delivery from 8.7 to 8.0 ml/100 ml/min (p less than 0.05) and cerebral blood volume from 4.9% to 4.6% (p less than 0.025) in the overall cortical gray matter. Our results indicate that hemodilution in the tested range does not improve oxygen transport or t...
Research Interests: Medicine, Stroke, Brain, Humans, Hemodynamics, and 13 moreAnesthesia, Clinical Sciences, Single Photon Emission Computed Tomography, Oxygen, Adult, Hemodilution, Cerebral Blood Flow, Reference Values, Neurosciences, Hematocrit, Oxygenation, Blood volume pulse, and Cardiovascular medicine and haematology
Research Interests:
Dysfunction of the brain occurring after local brain injury often improves clinically; however, the reason for this improvement has not been scientifically clarified. We used a new technique for imaging phosphoinositide turnover,... more
Dysfunction of the brain occurring after local brain injury often improves clinically; however, the reason for this improvement has not been scientifically clarified. We used a new technique for imaging phosphoinositide turnover, carbon-11-labeled diacylglycerol-positron emission tomography, to observe the process of recovery from injury in human brain. Patients with local brain injury exhibited radioactive spots located in the association areas distant from the lesion, while normal controls did not exhibit such spots. These findings indicated one of possible features of the neural recovery from the central nervous system injury, which appears to play a role in modulation of synaptic transmission in the intact brain. Conventionally, attention has been directed primarily to areas surrounding brain injury, such as the penumbra; however, the present study suggests that initiation of reorganization of neural connections occurs in remote cortex.
Research Interests: Neuroscience, Psychology, Cognitive Science, Treatment Outcome, Medicine, and 15 moreHumans, Female, Pubmed, Male, Central Nervous System, Human Brain, Middle Aged, Single Photon Emission Computed Tomography, Adult, Lesion, Diglycerides, Neurosciences, Case Control Studies, Brain injuries, and penumbra
Research Interests:
The Japanese orthography has some unique characteristics. Two types of Japanese characters, kana (phonetic symbols) and kanji (semantic and phonetic symbols), are used in combination. Although kana has simple forms and a limited number of... more
The Japanese orthography has some unique characteristics. Two types of Japanese characters, kana (phonetic symbols) and kanji (semantic and phonetic symbols), are used in combination. Although kana has simple forms and a limited number of characters, and kanji has complex forms and an infinite number of characters, Japanese aphasic patients often have trouble using kana characters properly. In the present case of crossed aphasia of a right-handed Japanese man due to a large hypertensive intracerebral hematoma in the right side, we also observed the impairment in kana processing. He could neither speak nor read aloud, but on multiple choice examinations, he could point to pronounced kanji letters. Although he could point to pronounced kana words, he could not point to kana letters. We will review some tachistoscopic studies of recognition and comprehension of the lateralized visual informations of kana and kanji for normal Japanese and for Japanese patients with disconnection syndrom...
Research Interests:
Research Interests:
ABSTRACT Most measurements of oxygen tension (PO(2)) in the brain have been performed using oxygen microelectrodes. However, the insertion of microelectrodes into the brain per se causes cortical injury and hence could lead to erroneous... more
ABSTRACT Most measurements of oxygen tension (PO(2)) in the brain have been performed using oxygen microelectrodes. However, the insertion of microelectrodes into the brain per se causes cortical injury and hence could lead to erroneous PO(2) measurements. The recently developed "quenching lifetime method" requires the injection of fluorescent chemicals into the blood circulation. To address this issue, we tested the feasibility of our O(2)-sensitive fluorescent membrane technique in the rat brain, and visualized the spatial distribution of PO(2) on the brain surface as epifluorescent microscopic patterns. An O(2)-quenching fluorescence dye, tris (1,10-phenanthroline) Ru(2+), was immobilized in a highly gas-permeable, thin silicone-rubber film formed on a microscope coverslip. Unlike the original method, which was intended for transparent rat mesenteric tissue, any change in the redox state in the brain tissue will influence the optical measurement of PO(2). Thus, in the present study, the O(2)-sensing membrane was further coated with a thin opaque silicone-rubber to minimize this type of influence. This new method enabled us to visualize the PO(2) gradient on the rat brain without causing cortical injuries. In an ischemia/reperfusion model using Pulsinelli's four-vessel occlusion rats, the changes in the PO(2) were highly heterogeneous during the ischemic period and this heterogeneity, both temporal and spatial, was higher in the off-arteriolar area than in the peri-arteriolar area.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
The uptake mechanism of 1,2-[11C]diacylglycerols (DAG) was studied and its use as a probe for the measurement of phosphatidylinositol (PI) turnover was verified. A method of synthesis for producing rac-1,2-[11C]DAG using [11C]ethylketene... more
The uptake mechanism of 1,2-[11C]diacylglycerols (DAG) was studied and its use as a probe for the measurement of phosphatidylinositol (PI) turnover was verified. A method of synthesis for producing rac-1,2-[11C]DAG using [11C]ethylketene was developed to label the 1- or 3-hydroxyl group of 2-monoacylglycerol. After intravenous injection, these tracers were metabolized rapidly in the rat brain cortex to phosphatidic acids, phosphatidylinositols and phosphatidylinositol phosphates. The brain cortex anesthetized by barbiturate, which represents inhibited state of synaptic transmission, did not produce differences in uptake values between sn-1,2-[11C]DAG and rac-1,2-[11C]DAG. However, in the liver, lung, and pancreas under the same conditions, the uptake values of rac-1,2-[11C]DAG were higher than those of sn-1,2-[11C] DAG, in which the labeling position was on the 2-hydroxyl group in the sn type. These findings suggest that the lipase activity in the brain should be disregarded because...
Research Interests:
Selective neutron capture therapy (NCT) using specific dopa analog,10B-p-boronophenylalanine (10B-L-BPA) for malignant melanoma of the skin was developed and achieved many cures by Mishima and his group1,2. We had developed... more
Selective neutron capture therapy (NCT) using specific dopa analog,10B-p-boronophenylalanine (10B-L-BPA) for malignant melanoma of the skin was developed and achieved many cures by Mishima and his group1,2. We had developed 18F-10B-L-Boronophenylalanine which can not only provide selective detection and three dimensional imaging, but also 10B concentration dynamics clinically using positron emission tomography (PET)3,4,5. The purpose of this study is to explore NCT of melanoma brain metastasis using this compound.
Research Interests:
Research Interests:
Receptor-mediated membrane processing plays an essential role in neural function in the synapses. In such neurotransmission process, the phosphoinositide (PI) response, an effector in the production of second-messengers, can be used to... more
Receptor-mediated membrane processing plays an essential role in neural function in the synapses. In such neurotransmission process, the phosphoinositide (PI) response, an effector in the production of second-messengers, can be used to assess in vivo signal transduction. Using in vivo autoradiography and positron emission tomography (PET), we attempted to visualize the PI response to muscarinic cholinergic receptor (mAChR)-stimulation in rats and monkeys, which were administered 1,2-[11C]diacylglycerol (DAG) intravenously. Enhancement of 1,2-[11C]DAG incorporation was observed in the rat ipsilateral hippocampus and cortex in which mAChR-agonist was administered by local injection, but this was in contrast to spreading cortical depression in the ipsilateral cortex using KCl. In monkey PET studies, dynamic brain scanning revealed increase in activity over time for about 15 min after a bolus injection of 1,2-[11C]DAG in an awake state. The activity then remained at a constant level. Th...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Humans, Glioma, Glioblastoma, PET imaging, Blood sampling, and 11 moreBoron Neutron Capture Therapy (BNCT), Clinical Sciences, Single Photon Emission Computed Tomography, Phenylalanine, Radiopharmaceuticals, Astrocytoma, Boron Compounds, Brain Neoplasms, Rate Constant, Compartment Model, and kinetic analysis
Research Interests: Japan, Stratification, X Rays, Humans, Glioblastoma, and 13 moreBoron Neutron Capture Therapy (BNCT), Clinical Sciences, Phenylalanine, Survival Rate, Prognosis, Malignant Glioma, Clinical Protocols, Boron Compounds, Brain Neoplasms, Tumor Progression, Combined Modality Therapy, Median Survival Time, and Borohydrides
Research Interests:
Research Interests:
Research Interests:
Research Interests:
The potential of 6-(¹â¸F)fluoro-L-fucose (6-(¹â¸F)FFuc) for assessing glycoconjugate synthesis in tumors with positron emission tomography (PET) was investigated. Using the tissue sampling method with five tumor models, different... more
The potential of 6-(¹â¸F)fluoro-L-fucose (6-(¹â¸F)FFuc) for assessing glycoconjugate synthesis in tumors with positron emission tomography (PET) was investigated. Using the tissue sampling method with five tumor models, different time-radioactivity profiles were found: a nearly constant level in Lewis lung carcinoma (3LL) and different clearance patterns in others. Rapid clearance in normal tissues resulted in preferable uptake ratios for tumor imaging of brain and pancreas. Metabolic studies and the L-fucose loading effects on the tissue uptake proved the tracer to be a biochemically active L-fucose analog. Imaging of the intracranial rat glioma and 3LL in lungs or hepatomas in mice by autoradiography (ARG) and intramuscular VX-2 carcinoma in rabbits by PET was demonstrated. Using double-radionuclide ARG, similar distribution images of 6-(¹â¸F)FFuc and ¹â´C-L-fucose but different tumor-to-liver uptake ratios were found. A metastasis model seemed to show a higher uptake of both tracers as compared to a primary tumor model.
Research Interests:
Research Interests:
Research Interests: Nuclear medicine, Adolescent, Coma, Brain, Humans, and 15 moreGlucose, Glucose Metabolism, Female, Male, Glasgow Coma Scale, Glycolysis, Brain injury, Clinical Sciences, Metabolic rate, Adult, Regional Cerebral Blood Flow, Oxygen Extraction Fraction, Oxygen Consumption, Brain injuries, and Cerebral Blood Volume
Research Interests:
Research Interests:
We recently reported that myocardial phosphoinositide (PI) metabolism can be visualised by 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol (11C-DAG) in rats with myocardial infarction (MI). Angiotensin II, the receptors for which are expressed... more
We recently reported that myocardial phosphoinositide (PI) metabolism can be visualised by 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol (11C-DAG) in rats with myocardial infarction (MI). Angiotensin II, the receptors for which are expressed predominantly in infarcted areas with active fibrogenesis rather than in non-infarcted regions, is involved in the upstream signalling systems of PI metabolism and plays an important role in the process of left
Research Interests:
Research Interests:
Phosphoinositide turnover mediates the signaling of angiotensin II, which plays a pivotal role in ventricular remodeling after myocardial infarction (MI). We tested the hypothesis that phosphoinositide turnover can be visualized by 1-[1... more
Phosphoinositide turnover mediates the signaling of angiotensin II, which plays a pivotal role in ventricular remodeling after myocardial infarction (MI). We tested the hypothesis that phosphoinositide turnover can be visualized by 1-[1 -(11)C]butyryl-2-palmitoyl-rac-glycerol (11C-DAG) in both infarcted and noninfarcted myocardium after MI in rats. Rats received an injection of 11C-DAG 7 d after left coronary artery ligation, and myocardial lipids were extracted from both infarcted and noninfarcted areas of myocardium (n = 3). Metabolites of 11C-DAG were determined by thin-layer chromatography. Quantitative autoradiography of hearts was performed to visualize myocardial phosphoinositide turnover in rats that received an injection of 11C-DAG 1 d (n = 3) and 7 d (n = 5) after MI and 7 d after a sham operation (n = 3). Quantitative autoradiography with 201TlCl was also performed to evaluate myocardial blood flow in rats 7 d after MI (n = 3). Cells occupying the infarcted myocardium wer...
Research Interests:
Previous neuroimaging studies in corticobasal degeneration (CBD), such as MRI and positron emission tomography, showed lateralized cortical atrophy and a decrease in cortical oxygen metabolism, respectively. The advantage of... more
Previous neuroimaging studies in corticobasal degeneration (CBD), such as MRI and positron emission tomography, showed lateralized cortical atrophy and a decrease in cortical oxygen metabolism, respectively. The advantage of magnetoencephalography in the research of the auditory system is that activity of both hemispheres can be detected separately. Auditory-evoked magnetic fields (AEFs) were then applied to a patient with corticobasal degeneration. The strength of N100m equivalent current dipoles (ECD) in left hemisphere was extremely smaller (20 nAm) than that in right hemisphere (48 nAm). This results implies that CBD patient might have a decrease in the number of neurons in the primary auditory cortex. This study suggests that AEF measurement is one of the most powerful tools for detecting latent impairment of auditory function in patients with corticobasal degeneration.
Research Interests:
We synthesized fluorine-18-labeled fluoroboronophenylalanine (18F-10B-FBPA), an analog of boronophenylalanine (10B-BPA), and characterized its pharmacokinetics in patients with glioma. We conducted PET studies on three types of gliomas to... more
We synthesized fluorine-18-labeled fluoroboronophenylalanine (18F-10B-FBPA), an analog of boronophenylalanine (10B-BPA), and characterized its pharmacokinetics in patients with glioma. We conducted PET studies on three types of gliomas to clarify the relationship between tumor grade and each rate constant [K1 (ml/g/min), k2 (min[-1]) and k3 (min[-1])], and here, we discuss the metabolism of the 10B-BPA analog (18F-10B-FBPA). Thirty-three cases of primary gliomas were studied by dynamic PET using DL-18F-10B-FBPA or L-18F-10B-FBPA. Dynamic PET images of 18F-10B-FBPA incorporation into tumors were obtained, and the arterial blood samplings were performed in all cases. When the dynamic PET data were represented as Gjedde-Patlak plots, there was a positive slope, suggesting the involvement of the putative metabolic pool of this tracer. A three-compartment model using rate constants (K1, k2 and k3) was used for the kinetic analysis. The accumulation of 18F-10B-FBPA was found to correlate ...
Research Interests: Humans, Glioma, Glioblastoma, PET imaging, Blood sampling, and 11 moreBoron Neutron Capture Therapy (BNCT), Clinical Sciences, Single Photon Emission Computed Tomography, Phenylalanine, Radiopharmaceuticals, Astrocytoma, Boron Compounds, Brain Neoplasms, Rate Constant, Compartment Model, and kinetic analysis
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),... more
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.
Research Interests:
To evaluate irradiation effects on the metabolism of metastatic brain tumors treated by Gamma Knife radiosurgery, positron emission tomography (PET) and 1H-magnetic resonance spectroscopy (MRS) studies were performed on five patients. The... more
To evaluate irradiation effects on the metabolism of metastatic brain tumors treated by Gamma Knife radiosurgery, positron emission tomography (PET) and 1H-magnetic resonance spectroscopy (MRS) studies were performed on five patients. The tumor origins were lung cancer in three patients and breast cancer in two. Treatment volume was 0.4-10.1 cm3 (mean: 5.5 cm3). The marginal dose to the tumor was 24-30 Gy (mean: 26.2 Gy). The follow-up period was 5-19 months (mean: 13.4 months). No patients had conventional whole-brain radiation therapy. 18F-fluoroboronophenylalanine (18FBPA) or 18F-fluorodeoxyglucose (18FDG) were used as tracers for the PET study. Using 1H-MRS, several metabolites were simultaneously measured in metastatic brain tumor and adjacent brain. In the PET study of the representative case, the uptake rate of 18FBPA that is actively transported to the tumor decreased markedly 15 days after radiosurgery and continued to decrease thereafter. In the 1H-MRS study, choline, whic...
Research Interests: Breast Cancer, Radiosurgery, Magnetic Resonance Spectroscopy, Positron Emission Tomography, Lung Cancer, and 15 moreBrain Tumor, Cell Differentiation, Humans, Female, Male, Aged, Middle Aged, Radiation Effect, Necrosis, Active Transport, Protons, Brain Neoplasms, Cell Membrane, proton magnetic resonance spectroscopy, and Whole brain radiation therapy
Cerebral hemodynamics and metabolism in three patients with severe diffuse brain injury were measured 10 days after onset using PET. In this study, regional cerebral blood flow (rCBF), oxygen extraction fraction (rOEF), cerebral blood... more
Cerebral hemodynamics and metabolism in three patients with severe diffuse brain injury were measured 10 days after onset using PET. In this study, regional cerebral blood flow (rCBF), oxygen extraction fraction (rOEF), cerebral blood volume (rCBV), cerebral metabolic rate for oxygen (rCMRO2), cerebral metabolic rate for glucose (rCMRglc) and cerebral metabolic ratio (rCMRO2/rCMRglc) were measured. The Glasgow Coma Scale scores on admission were 4, 5 and 5, respectively, and CT on admission showed typical findings of diffuse brain injury. As a result, PET revealed misery perfusion and hyperglycolysis in Patient 1 and matching low perfusion and low glucose metabolism in Patients 2 and 3. Although Patient 1 died, Patients 2 and 3 had good recoveries. We speculate that a long-lasting anaerobic state, indicated by a high OEF value and low metabolic ratio, is an important undesirable factor related to the outcome.
Research Interests: Nuclear medicine, Adolescent, Coma, Brain, Humans, and 15 moreGlucose, Glucose Metabolism, Female, Male, Glasgow Coma Scale, Glycolysis, Brain injury, Clinical Sciences, Metabolic rate, Adult, Regional Cerebral Blood Flow, Oxygen Extraction Fraction, Oxygen Consumption, Brain injuries, and Cerebral Blood Volume
Protein kinase C plays a crucial role in signal transduction for a variety of biologically active substances which activates cellular functions and their proliferation. The actions are closely related to both normal and abnormal functions... more
Protein kinase C plays a crucial role in signal transduction for a variety of biologically active substances which activates cellular functions and their proliferation. The actions are closely related to both normal and abnormal functions in the nervous system. Tumor-promoting phorbol esters can substitute for diacylglycerols which are important ligands that bind to protein kinase C. Three typical phorbol esters, phorbol 13-[1-11C]butyrate, phorbol 12,13-[1-11C]dibutyrate and 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate, were synthesized by using [11C]ethylketene with a high specific activity (186GBq/mumol). Their in vivo autoradiograms demonstrated a heterogenous distribution in rat brain. 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate was particularly suited for in vivo use due to its nontumor-promoting activity and its ready permeability to the blood-brain barrier. High optical density was observed in the cortex, amygdala and hippocampus. The in vivo binding properties of...