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Biomedical subjects

J Hatazawa

Publications and source records attributed to J Hatazawa.

At least 127 records · Page 7Linked to original sources
PubMed1992

A unique in vivo assessment of 4-[10B]borono-L-phenylalanine in tumour tissues for boron neutron capture therapy of malignant melanomas using positron emission tomography and 4-borono-2-[18F]fluoro-L-phenylalanine.

A unique in vivo approach to assessing the concentrations of 4-[10B]borono-L-phenylalanine (L-BPA), a melanoma targeting compound for boron neutron capture therapy (BNCT), was investigated using L-BPA labelled with positron-emitting 18F (half-life = 110 min), i.e., 4-[10B]borono-2-[18F]fluoro-L-phenylalanine (L-[18F]FBPA). High melanoma uptake of L-[18F]FBPA was reduced slightly by competition with L-BPA in the two animal models of the murine B16 melanoma and the melanotic Greene's melanoma No. 179 in hamsters. In mice given L-[18F]FBPA and L-BPA, the concentrations of 10B in B16 estimated from 18F radioactivity were lower than those measured by inductively coupled plasma-atomic emission spectroscopy. Lower estimated values were dependent on the time after injection and on the loading dose of L-BPA. The estimated 10B concentrations for Green's melanomas were comparable to the measured values. Positron emission tomography (PET) using L-[18F]FBPA allowed Greene's melanomas to be clearly visualized. In conclusion, when L-[18F]FBPA is used as a probe for L-BPA in BNCT of malignant melanomas, the melanoma can be localized and the 10B concentrations in tissues can be assessed in vivo using 18F radioactivity by PET.

Animals↗
PubMed1992

Mapping of histamine H1 receptors in the human brain using [11C]pyrilamine and positron emission tomography.

We have studied the characteristics of carbon-11 labeled pyrilamine as a radioligand for investigating histamine H1 receptors in human brain with positron emission tomography (PET). [11C]Pyrilamine is distributed evenly in proportion to cerebral blood flow at initial PET images. Later (after 45-60 min), 11C radioactivity was observed at high concentrations in the frontal and temporal cortex, hippocampus, and thalamus, and at low concentrations in the cerebellum and pons. The regional distribution of the carbon-11 labeled compound in the brain corresponded well with that of the histamine H1 receptors determined in vitro in autopsied materials. In six controls, the frontal and temporal cortices/cerebellum ratio increased during the first 60 min to reach a value of 1.22 +/- 0.071. Intravenous administration of d-chlorpheniramine (5 mg) completely abolished the specific binding in vivo in the frontal cortex and temporal cortex (cortex/cerebellum ratio, 0.955 +/- 0.015). The availability of this method for measuring histamine H1 receptors in vivo in humans will facilitate studies on neurological and psychiatric disorders in which histamine H1 receptors are thought to be abnormal.

Adult↗
PubMed1992

[A method for measurement of regional cerebral blood flow using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) SPECT; two scans with one point blood sampling technique].

We have developed a new method to quantitate regional cerebral blood flow (CBF) using 123I-IMP and SPECT. This technique requires two SPECT scans and one blood sampling. Based on the 2 compartment model (influx; k1 and outflux; k2), a table between k2 and ratio of 1st scan counts/2nd scan counts was calculated, and a table look up procedure yielded a unique pair of k1 (CBF) and distribution volume (Vd = k1/k2) for each region of interest (ROI). The arterial input function was obtained by one point blood sampling to calibrate the standard input function, which has been obtained from the previous study on 12 subjects. This method was applied to 5 subjects including 1 healthy volunteer and 4 patients with cerebral infarction, and the regional CBF results were compared with those measured by H2(15)O PET technique. Optimized scan time combination was 40, 180 min which provided the best correlation with H2(15)O-CBF. The Vd values obtained in infarcted regions were significantly smaller than those in normal regions, suggesting the importance of measuring Vd for each ROI.

Aged↗
PubMed1992

Cerebral blood flow and glucose metabolism measurements in a patient surviving one year after carbon monoxide intoxication.

A 29-yr-old woman was studied for 1 yr after acute carbon monoxide intoxication following an attempted suicide by inhalation of automobile exhaust fumes. The patient demonstrated impaired responsiveness to stimuli without any specific neurological deficits for 1 yr after carbon monoxide intoxication. Repeated brain magnetic resonance imaging consistently displayed only bilateral globus pallidus lesions, but no lesions in either deep white matter or cerebral cortex. Position emission tomography measurements of regional cerebral blood flow, and glucose utilization rate were made in this patient at 6 mo and 1 yr following carbon monoxide intoxication. Impairment of both blood flow and glucose metabolism were found not only in the basal ganglia but also in morphologically normal frontal cortex. The decrease in glucose utilization in the frontal cortex was greater than that in the basal ganglia. During the period of 6 mo to 1 yr, blood flow and glucose metabolism in the basal ganglia recovered to the normal range. In the frontal cortex, however, blood flow and glucose metabolism remained approximately 20% lower than the normal mean values. This prolonged dysfunction in the frontal cortex may therefore be responsible for the impaired responsiveness of the subject.

Adult↗
PubMed1991

Labeling of histamine H1-receptors in vivo: a compartment model analysis and positron emission tomographic imaging.

Binding of [3H]-pyrilamine to guinea-pig brain in vivo was studied and analyzed kinetically on the basis of a four-compartment model to establish the method of analysis for the in vivo binding. The pharmacological properties of the [3H]-pyrilamine binding in vivo were similar to those of the in vitro binding to brain homogenate. The distribution of histamine H1-receptors in dog brain, which was obtained by positron emission tomography (PET) with [11C]-pyrilamine or doxepin as a tracer, was in good correlation to that obtained by the in vitro binding method. We finally applied this in vivo binding method to a living healthy human to reveal the distribution of H1-receptor in the brain.

Animals↗
PubMed1991

Measurement of L-[methyl-11C]methionine in human plasma.

The routine measurement of L-[methyl-11C]methionine in human plasma after i.v. injection of the tracer is described. The protein-free plasma metabolites of the tracer were analyzed using a cation-exchange column (Aminex A-6) eluted with a pH 4.25 citrate buffer. The ratios of L-[methyl-11C]methionine for the total radioactivity decreased gradually, and the standard deviations among 19 humans were relatively small for 30 min: 97.2 +/- 1.4%, 5 min; 92.6 +/- 2.1%, 10 min; 89.4 +/- 4.0%, 15 min; 84.1 +/- 3.1%, 20 min; 73.1 +/- 9.8%, 30 min; 45.0 +/- 16.8%, 60 min. A convenient analysis using a Bond elute SCX cartridge showed slightly larger ratios than those measured by liquid chromatography.

Adolescent↗
PubMed1991

Absorbed dose estimates in positron emission tomography studies based on the administration of 18F-labeled radiopharmaceuticals.

Absorbed doses were estimated after intravenous administration of 18F-labeled radiopharmaceuticals in Positron Emission Tomography (PET) studies. These radiopharmaceuticals, [18F]-2-Fluoro-2-Deoxy-D-Glucose (FDG), 6-[18F]Fluoro-L-Dopa (FDOPA) and 18F-5-Fluorodeoxyuridine (FdUR), are used in clinical research at the Cyclotron and Radioisotope Center of Tohoku University. Radiopharmaceutical biokinetic values were measured in humans or extrapolated from animal experiments. Selective organ uptake and rapid clearance of activity from the blood were observed. High activity in the bladder contents of humans was found. Calculations were made by the MIRD method, modified to account for the differences in physique and organ mass between the Caucasian Reference Man and the Japanese one. The bladder wall receives the highest dose (more than 1.23 x 10(-1) mGy/MBq) when any of these compounds are administered. Other organs receiving high doses are the heart, brain and kidneys from FDG; the kidneys and pancreas from FDOPA, and the kidneys and small intestine from FdUR. These organs received absorbed doses of more than 2.7 x 10(-2) mGy/MBq. Effective dose equivalents of 2.4 x 10(-2), 2.6 x 10(-2) and 3.3 x 10(-2) mSv/MBq were estimated in the intravenous administration of 18F-FDG, 18F-FDOPA and 18F-FdUR, respectively.

Adult↗
PubMed1991

Measurement of D2 dopamine receptor-specific carbon-11-YM-09151-2 binding in the canine brain by PET: importance of partial volume correction.

Carbon-11-YM-09151-2 binds highly selectively to D2 dopamine receptors in the brain. Using this ligand, D2 dopamine receptor density (Bmax) and affinity (Kd) in canine striatum were measured. After administering various doses of the ligand in nine experiments, regional uptake was followed by repeated PET scanning for up to 80 min. D2 dopamine receptor specific binding at equilibrium was defined as striatal minus occipital activity after partial volume correction. Bmax and Kd were estimated by Scatchard analysis to be 40.3 pmole/ml of tissue and 22.9 nM, respectively. When a low mass dose of the ligand was administered, the bound-to-free ligand ratio in the striatum at equilibrium was consistent with the Bmax/Kd value obtained from the Scatchard analysis. The present study demonstrates the importance of partial volume correction and the Bmax/Kd measurement in a single PET study with carbon-11-YM-09151-2.

Animals↗
PubMed1991

Estimation of absorbed doses in humans due to intravenous administration of fluorine-18-fluorodeoxyglucose in PET studies.

Radiation absorbed doses due to intravenous administration of fluorine-18-fluorodeoxyglucose in positron emission tomography (PET) studies were estimated in normal volunteers. The time-activity curves were obtained for seven human organs (brain, heart, kidney, liver, lung, pancreas, and spleen) by using dynamic PET scans and for bladder content by using a single detector. These time-activity curves were used for the calculation of the cumulative activity in these organs. Absorbed doses were calculated by the MIRD method using the absorbed dose per unit of cumulated activity, "S" value, transformed for the Japanese physique and the organ masses of the Japanese reference man. The bladder wall and the heart were the organs receiving higher doses of 1.2 x 10(-1) and 4.5 x 10(-2) mGy/MBq, respectively. The brain received a dose of 2.9 x 10(-2) mGy/MBq, and other organs received doses between 1.0 x 10(-2) and 3.0 x 10(-2) mGy/MBq. The effective dose equivalent was estimated to be 2.4 x 10(-2) mSv/MBq. These results were comparable to values of absorbed doses reported by other authors on the radiation dosimetry of this radiopharmaceutical.

Adult↗
PubMed1990

Visualization of histamine H1 receptors in dog brain by positron emission tomography.

Histamine H1 receptors were visualized in the living dog brain using [11C]pyrilamine or [11C]doxepin by positron emission tomography (PET). The regional distribution of these carbon-11 labeled compounds in the brain corresponded well with that of the histamine H1 receptors separately determined by in vitro binding assay. The radioactivity in the brain was reduced by treatment with triprolidine (1 mg/kg), a histamine H1 antagonist. The results of our study indicate that it is feasible to visualize histamine H1 receptors in human brain using these 11C-labeled compounds and PET.

Animals↗
PubMed1990

Cerebral circulation and oxygen metabolism associated with subclinical periventricular hyperintensity as shown by magnetic resonance imaging.

A combined magnetic resonance imaging and positron emission tomography study was performed on 21 patients with cerebrovascular risk factors but without neurological abnormalities. Our purpose was to investigate the hypothesis that periventricular hyperintensity (PVH) reflects ischemia. Periventricular hyperintensity was evaluated with a method we devised, and cerebral circulation and oxygen metabolism were evaluated with the oxygen-15 steady-state technique. We concluded that the brain with severe periventricular hyperintensity had abnormal circulation, although oxygen metabolism was not measurably affected. The role of a compensation mechanism under conditions of decreased oxygen supply was considered.

Aged↗
PubMed1990

The accumulation of 11C-methionine in cerebral glioma patients studied with PET.

Fourteen patients with cerebral gliomas were studied with positron emission tomography (PET) using L-[methyl-11C]methionine (11C-MET). Positive images of tumour were obtained in all cases regardless of histological grades. The analysis of differential absorption ratio (DAR) showed the higher accumulation of 11C-MET in high grade gliomas than in low grade gliomas. PET study with 11C-MET will be of great value not only in delineating the location of gliomas, but also in making a qualitative diagnosis from the view point of the biological properties of gliomas.

Adult↗
PubMed1990

Clinical assessment of therapeutic effects on cancer using 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography: preliminary study of lung cancer.

Using positron emission tomography, we studied the tumor uptake of 18F-2-fluoro-2-deoxy-D-glucose (18FDG) in five lung cancer patients before and after anti-cancer therapy (radiotherapy and/or chemotherapy). The tumor uptake of 18FDG was classified as positive and negative; the former, by increasing the uptake of 18FDG with time, and the latter, by decreasing or the constant uptake of 18FDG. Before therapy, all cases tested positive. After therapy, three cases were negative and two cases remained positive. All negative cases corresponded to complete second 18FDG study. Our findings in the 18FDG study correlate with the clinical results. 18FDG is a promising method for assessing therapeutic effects on cancer clinically.

Adult↗
PubMed1990

Synthesis of omega-[18F]fluoroalkyl analogs of YM-09151-2 for the measurement of D2-dopamine receptors with PET.

Two [18F]fluoroalkyl analogs of a neuroleptic YM-09151-2 were synthesized via nucleophilic [18F]fluorination of methanesulfonyloxy- or p-toluenesulfonyloxyalkyl derivatives using no-carrier-added [18F]fluoride. Although 3-[18F]fluoropropylaminobenzamide was obtained in good yield, the yield of 2-[18F]fluoroethyl derivative was severalfold lower. The product, N-[(2RS,3RS)-1-benzyl-2-methylpyrrolidin-3-yl]-5- chloro-2-methoxy-4-(3-[18F]fluoropropyl)-aminobenzamide, was shown to have a striatum-to-cerebellum ratio comparable to that of 11C labeled YM-09151-2 and thus to be a good candidate for measuring D2-receptors in vivo.

Animals↗
PubMed1990

Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age.

Regional cerebral blood flow (CBF), oxygen extraction ratio (OER), oxygen utilization (CMRO2) and blood volume (CBV) were measured in a group of 34 healthy volunteers (age range 22-82 yrs) using the 15O steady-state inhalation method and positron emission tomography. Between subjects CBF correlated positively with CMRO2, although the interindividual variability of the measured values was large. OER was not dependent on CMRO2, but highly negatively correlated with CBF. CBV correlated positively with CBF. When considering the values of all the regions of interest within a single subject, a strict coupling between CMRO2 and CBF, and between CBF and CBV was found, while OER was constant and independent of CBF and CMRO2. In 'pure' grey and white matter regions CMRO2, CBF and CBV decreased with age approximately 0.50% per year. In other regions the decline was less evident, most likely due to partial volume effects. OER did not change or showed a slight increase with age (maximum in the grey matter region 0.35%/yr). The results suggest diminished neuronal firing or decreased dendritic synaptic density with age.

Adult↗
PubMed1990

Stability of cerebral blood flow and oxygen metabolism during normal aging.

Cerebral blood flow and oxygen metabolism in aged normal subjects were measured with positron emission tomography and their relationship with brain atrophy was evaluated. Brain atrophy progressed in a linear fashion during aging while cerebral blood flow and oxygen metabolism were well preserved. The finding suggests that brain atrophy is an aging process less dependent on cerebral blood flow and metabolism over the course of normal aging.

Aged↗