Toru Sasaki - Academia.edu (original) (raw)
Papers by Toru Sasaki
RADIOISOTOPES
A growth hormone deficiency is associated with increases in body fat. However, it currently remai... more A growth hormone deficiency is associated with increases in body fat. However, it currently remains unclear whether subcutaneous-or/and intra-abdominal adipose tissues are markedly elevated in dwarf obesity. Experiments were conducted on the spontaneous dwarf rats (SDRs) and normal Sprague-Dawley (SD) rats using an X-ray computed tomography scanner to determine body composition. A longitudinal study of aging was also conducted to track age-related changes in body composition using same animals. We succeeded to estimate the subcutaneous and intra-abdominal adipose tissue mass in rat by X-ray CT. SDRs demonstrated the dwarf obesity, but SDs did not. SDRs developed dwarf obesity due to the accumulation of subcutaneous-abdominal adipose tissue, but not intra-abdominal adipose tissue. Age-dependent increases in the abdominal adipose tissue were observed in both SDRs and SDs. However, age-dependent increases in intra-abdominal adipose tissue were greater than in subcutaneous-abdominal adipose tissue.
Eur J Nucl Med, 1986
The relationship between 67Ga uptake and heparan sulfate (HS) content in Ehrlich solid tumor (EST... more The relationship between 67Ga uptake and heparan sulfate (HS) content in Ehrlich solid tumor (EST) of mice was investigated, and the effect of cyanomethylamine, papain, streptozotocin, or bleomycin pretreatment on 67Ga uptake in EST was studied. 67Ga uptakes in EST and kidney were much higher than other tissues, and these tissues also contained large amounts of HS. 67Ga uptakes and HS synthesis in the EST were inhibited by pretreatment with cyanomethylamine or papain (inhibitors of fibrosis). Parallel reductions of 67Ga uptake and HS synthesis in EST were observed in EST transplanted into streptozotocin-induced diabetic mice. The weight of EST in the bleomycin-injected group was decreased to less than half of the control, but no effect was observed on 67Ga uptake per gram of EST. These results suggest that 67Ga uptake in the tumor and inflammatory lesions are related to the quantity of HS in these tissues, and the correlation between the uptake of 67Ga and the rate of cellular proliferation is secondary.
Annals of Nuclear Medicine, Jun 1, 2008
K 1 of 11 C-SA4503 correlated with rCBF, but the other three rate constant parameters and BP did ... more K 1 of 11 C-SA4503 correlated with rCBF, but the other three rate constant parameters and BP did not. The regional difference in the BP of 11 C-SA4503 is compatible with those of sigma 1 receptors. In conclusion, successive PET measurements of rCBF and the brain kinetics of radioligand-neuroreceptor binding are useful for the fi rst clinical trial of a newly developed radioligand for mapping neuroreceptors, and the protocol is applicable to pathophysiological studies of brain disorders.
Ann Nucl Med, 2003
We report the first clinical PET study using [1-methyl-11 C]8-dicyclopropylmethyl-1-methyl-3propy... more We report the first clinical PET study using [1-methyl-11 C]8-dicyclopropylmethyl-1-methyl-3propylxanthine ([ 11 C]MPDX) for imaging adenosine A1 receptors in the human brain. The binding of [ 11 C]MPDX evaluated quantitatively as the distribution volume by a graphical analysis was high in the striatum and thalamus, and low in the cerebellum. The distribution pattern of [ 11 C]MPDX was coincident with that of adenosine A1 receptors in vitro reported previously, and was different from those of blood flow and [ 18 F]FDG. The [ 11 C]MPDX PET has the potential for mapping adenosine A1 receptors in the human brain.
Journal of Nuclear Medicine, Oct 1, 1996
To visualize the regional localization of glutathione (GSH) in the brain, the relationship betwee... more To visualize the regional localization of glutathione (GSH) in the brain, the relationship between the concentrations of tissue GSH and uptake of [""Tcyneso-hexamethyl propyleneamine oxime ([""Te] meso-HMPAO) or [99nrTc]d,/-hexamethyl propyleneamine oxime ([""TcJoV-HMPAO) was studied in mice. Methods: The uptake of [^"TcJmeso-HMPAO in the mouse brain was decreased to 35% of control paralleling the decrease in GSH content by pre-loading of diethyl maléate(DEM), an agent to reduce GSH. in contrast, pre treatment with DEM scarcely affected the ""Tc-oV-HMPAO uptake in the brain. Results: The DEM treatment decreased the GSH content in liver, kidney, spleen, fat and lung but did not affect the uptake of [""^cJmeso-HMPAO in those tissues except lung. The images of rat brain acquired with a gamma camera showed a significant reduction of [""TcJmeso-HMPAO uptake by DEM treat ment. Conclusion: Technetium-99m-meso-HMPAO may be a po tential tool to assess GSH content and to estimate antioxidative ability in the brain.
Ann Nucl Med, 2008
K 1 of 11 C-SA4503 correlated with rCBF, but the other three rate constant parameters and BP did ... more K 1 of 11 C-SA4503 correlated with rCBF, but the other three rate constant parameters and BP did not. The regional difference in the BP of 11 C-SA4503 is compatible with those of sigma 1 receptors. In conclusion, successive PET measurements of rCBF and the brain kinetics of radioligand-neuroreceptor binding are useful for the fi rst clinical trial of a newly developed radioligand for mapping neuroreceptors, and the protocol is applicable to pathophysiological studies of brain disorders.
Eur J Nucl Med, 1984
67Ga incorporation in the mitochondrial-lysosomal (Mt-Ly) fraction of rat liver increased sharply... more 67Ga incorporation in the mitochondrial-lysosomal (Mt-Ly) fraction of rat liver increased sharply from 1 to 24 h after 67Ga IV injection, whereas that in the 105,000 g supernatant fraction decreased sharply from 6 to 48 h. Further, when 14C-labeled heparan sulfate (HS: biosynthesized by injection of [1-14C] glucosamine into a rat) was injected intravenously into a rat treated with Triton WR-1339, and the liver was isolated and fractionated, the radioactivity of 14C was concentrated in the lysosomal fraction. The effect of HS on 67Ga uptake in normal rat liver was also studied. On administration of 67Ga-HS complex, the peak uptake of administered radioactivity of 67Ga in rat liver occurred sooner than after the injection of 67Ga alone. The change was greatest in the Mt-Ly fraction among the subcellular fractions. Moreover, the 67Ga uptake in rat liver increased with increasing doses of HS. These results suggest that administered 67Ga may be bound to HS and that the concentration of 67Ga in lysosomes may be related to the in vivo metabolism of HS.
![Research paper thumbnail of Intrasubject correlation between static sean and distribution volume images for [ 11 C]flum](https://attachments.academia-assets.com/71503153/thumbnails/1.jpg)
](Ann Nucl Med, 2000
Accumulation of [i IC]flumazenil (FMZ) reflects central nervous system benzodiazepine receptor (B... more Accumulation of [i IC]flumazenil (FMZ) reflects central nervous system benzodiazepine receptor (BZR). We searched for the optimal time for a static PET scan with FMZ as semi-quantitative imaging of BZR distribution. In 10 normal subjects, a dynamic series of decay-corrected PET scans was performed for 60 minutes, and the arterial blood was sampled during the scan to measure radioactivity and labeled metabolites. We generated 13 kinds of "static scan" images from the dynamic scan in each subject, and analyzed the pixel correlation for these images versus distribution volume (DV) images. We also analyzed the time for the [l 1C]FM Z in plasma and tissue to reach the equilibrium. The intra-subject pixel correlation demonstrated that the "static scan" images for the period centering around 30 minutes post-injection had the strongest linear correlation with the DV image. The ratio of radioactivity in the cortex to that in the plasma reached a peak at 40 minutes after injection. Considering the physical decay and patient burden, we conclude that the decay corrected static scan for [l tC]FM Z PET as semi-quantitative imaging of BZR distribution is to be optimally acquired from 20 to 40 minutes after injection.
Nucl Med Biol, 2005
We examined the densities of adenosine A2A receptors in cardiac and skeletal muscles between untr... more We examined the densities of adenosine A2A receptors in cardiac and skeletal muscles between untrained and endurance-trained subjects using positron emission tomography (PET) and [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX), a newly developed radioligand for mapping adenosine A2A receptors. Five untrained and five endurance-trained subjects participated in this study. The density of adenosine A2A receptors was evaluated as the distribution volume of [11C]TMSX in
Cancer Research, Jan 15, 1994
Tumor imaging with labeled liposomes is slow; although they reach the tumor quickly, their blood ... more Tumor imaging with labeled liposomes is slow; although they reach the tumor quickly, their blood clearance is slow, and the high blood background hinders early imaging. We have developed a rapid tumor imaging technique based on the active removal of liposomes from the circulation by using the avidin-biotin system. 67Ga-or lnIn-labeled liposomes with biotin molecules bound on the surface were administered to mice bearing sarcoma 180, and avidin was administered 2 h later. The strong affinity between biotin and avidin initiated the aggregation of liposomes, resulting in their rapid removal from the circulation by the reticuloendotheliai system, and the blood level of radioactivity was dramatically reduced without any change of the tumor level. Consequently, the tumor:blood ratio reached 14-18 only 2.5 h after liposome injection. Increased accumulation in the liver was also observed. By this method, an acceptable tumor image could be obtained no more than 2 h after administration of labeled liposomes.
Ann Nucl Med, 2008
Methods We studied fi ve AD patients and seven elderly volunteers. A dynamic series of decay-corr... more Methods We studied fi ve AD patients and seven elderly volunteers. A dynamic series of decay-corrected PET data acquisition was performed for 90 min starting at the time of the injection of 500 MBq of [ 11 C]SA4503. A twotissue three-compartment model was used to estimate K 1 , k 2 , k 3 , k 4 , and the delay between metabolite-corrected plasma and tissue time activity using a Gauss-Newton algorithm. The ratio of k 3 to k 4 was computed as the binding potential (BP), which is linearly related to the density of sigma 1 receptors. Unpaired t tests were used to compare K 1 and BP in patients with AD and normal subjects. Results As compared with normals, BP in the AD was signifi cantly lower in the frontal, temporal, and occipital lobe, cerebellum and thalamus, whereas K 1 was significantly lower in the parietal lobe. Conclusions [ 11 C]SA4503 PET can demonstrate that the density of cerebral and cerebellar sigma 1 receptors is reduced in early AD.
y-glutamylcysteine synthetase. In an in vitro study, ""Tc-HMPAO showed reactivity to th... more y-glutamylcysteine synthetase. In an in vitro study, ""Tc-HMPAO showed reactivity to the molecules possessing a -SH group, but were not specific to GSH. The order of 99rTTc-meso-HMPAOreac tivity to the mouse brain homogenate agreed with the order of GSH concentration: normal > BSO > DEM. GSH was a major contribu tor to the conversion reaction of ""Tc-meso-HMPAO to hydrophilic complex
Oxidative medicine and cellular longevity, 2015
Oxidative stress is believed to greatly contribute to the pathogenesis of various diseases, inclu... more Oxidative stress is believed to greatly contribute to the pathogenesis of various diseases, including neurodegeneration. Impairment of mitochondrial energy production and increased mitochondrial oxidative damage are considered early pathological events that lead to neurodegeneration. Manganese superoxide dismutase (Mn-SOD, SOD2) is a mitochondrial antioxidant enzyme that converts toxic superoxide to hydrogen peroxide. To investigate the pathological role of mitochondrial oxidative stress in the central nervous system, we generated brain-specific SOD2-deficient mice (B-Sod2 (-/-)) using nestin-Cre-loxp system. B-Sod2 (-/-) showed perinatal death, along with severe growth retardation. Interestingly, these mice exhibited spongiform neurodegeneration in motor cortex, hippocampus, and brainstem, accompanied by gliosis. In addition, the mutant mice had markedly decreased mitochondrial complex II activity, but not complex I or IV, in the brain based on enzyme histochemistry. Furthermore, b...
ANTI-AGING MEDICINE, 2011
Objective: We previously found that green tea catechins (GT-catechin) decrease oxidative damage t... more Objective: We previously found that green tea catechins (GT-catechin) decrease oxidative damage to DNA and suppress brain dysfunction in aged senescence-accelerated mice (SAMP10). To clarify the effect of GT-catechin on suppression of brain dysfunction, we compare the effect on learning ability among several catechins and examined the essential intake period for prevention of brain dysfunction. Methods: Male SAMP10 mice were allowed free access to water containing epigallocatechin gallate (EGCG, 0.06 mg/ml), epigallocatechin (EGC, 0.03 mg/ml), GT-catechin (0.2 mg/ml), or green tea extract (0.66 mg/ml). Learning ability of mice was measured using a step-through passive avoidance task. Results: SAMP10 mice exhibit brain dysfunction with aging. However, learning ability was significantly higher in mice that drank GT-catechin and EGCG than same-aged control mice that drank water. EGCG was an important component, but EGC had no effect on learning ability. The learning ability was significantly improved in mice that ingested EGCG for >5 months, and tended to improve in mice that ingested EGCG for 2 or 3 months. Next, the level of synaptophysin, a marker of presynapse, tended to be higher in mice that ingested EGCG but not in mice that ingested EGC. The levels of synaptophysin were significantly higher in mice ingested GT-catechin and green tea extract than control mice. Conclusion: The intake of EGCG, the major catechin in green tea, but not EGC, suppressed age-related brain dysfunction. The effective intake period of EGCG was > 5 months for suppression of brain dysfunction.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1998
The aim of this study was to explain the contribution of mitochondria to the accumulation of 99mT... more The aim of this study was to explain the contribution of mitochondria to the accumulation of 99mTc-meso-hexamethyl propyleneamine oxime (HMPAO) in the brain, after examinations were performed. We studied subcellular distribution of 99mTc-meso-HMPAO and glutathione (GSH) in normal and diethyl maleate (DEM)-administered mice. In normal brain, major radioactivity was found in the mitochondrial (49.0%) and cytosolic fractions (33.0%), while the GSH content was high in the cytosol (63.2%) and mitochondria (30.6%). The radioactivity in mitochondrial, cytosolic, microsomal and nuclear fractions was decreased in a dose-dependent manner by DEM, a GSH depleting agent, to 32.2% (mitochondrial) and 24.7% (cytosolic) of the control by a dose of 550 mg/kg. The GSH content in mitochondrial and cytosolic fractions also decreased in a dose-dependent manner on DEM treatment to 29.3% (mitochondrial) and 30.0% (cytosolic) of the control by 550 mg/kg of DEM. A good correlation was found between the upta...
International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology, 1992
Various radionuclide-ligand complexes were encapsulated in liposomes and their accumulations in t... more Various radionuclide-ligand complexes were encapsulated in liposomes and their accumulations in tumors were studied. Increased tumor accumulation was observed with every complex in the liposome-encapsulated form. However, different accumulation levels were registered for the various radionuclides even though they were all delivered using a similar liposome formulation. Though the liposomes remained intact in the circulation, they were degraded in the tumor, liver and spleen eventually. Thus, this suggests that tumor accumulation of liposome-encapsulated radionuclides is dependent on not only the in vivo behavior of the liposomes themselves, but also the characteristics of nuclide-ligand complexes after their release from liposomes. A correct choice of radionuclides and ligands for encapsulation in liposomes would enable excellent tumor-imaging agents to be achieved.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1999
The relationship between distribution of 99mTc meso-hexamethyl propyleneamine oxime (HMPAO) and g... more The relationship between distribution of 99mTc meso-hexamethyl propyleneamine oxime (HMPAO) and glutathione (GSH) content was studied in the mouse. The regional distributions of 99mTc meso-HMPAO and 99mTc d,I-HMPAO were examined using tissue sampling and autoradiographic methods and were compared with GSH content and distribution by a histochemical procedure. The uptake of 99mTc meso-HMPAO was highest in the cerebellum and lowest in the brain stem, whereas the distribution of 99mTc d,I-HMPAO was more uniform. The regional distribution of 99mTc meso-HMPAO in the mouse brain correlated with GSH content (r = 0.787), but that of 99mTc d,I-HMPAO did not. Treatment with diethyl maleate, a GSH depletor, significantly decreased the 99mTc meso-HMPAO uptake to 21%-33% of the control in every region, but the reduction of the 99mTc d,I-HMPAO uptake was moderate (58%-65% of the control). In the autoradiograph, the radioactivity of 99mTc meso-HMPAO was higher in the gray matter than in the white ...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1997
To clarify whether the content of glutathione (GSH) in the brain can be estimated by the uptake o... more To clarify whether the content of glutathione (GSH) in the brain can be estimated by the uptake of 99mTc-meso-HMPAO, we conducted the following in vivo and in vitro experiments. We investigated the effect of diethyl maleate (DEM) and buthionine sulfoximine (BSO) administration on the brain uptake of 99mTc-meso-HMPAO in the mouse, rat and rabbit, and the chemical specificity of in vitro interaction of 99mTc-HMPAO to GSH using measurements of octanol-extractable radioactivity as an index of remaining intact tracer. The uptake of 99mTc-meso-HMPAO in the mouse and rat brain were reduced together with decreased content of GSH by preloading of DEM, a GSH depletor that acts through glutathione S-transferase. Neither 99mTc-meso-HMPAO uptake nor GSH content was affected in the rabbit brain. Similarly, the uptake of 99mTc-meso-HMPAO and GSH content in the mouse brain was reduced by preinjection of BSO, a GSH depletor that acts through gamma-glutamylcysteine synthetase. In an in vitro study, 9...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1996
To visualize the regional localization of glutathione (GSH) in the brain, the relationship betwee... more To visualize the regional localization of glutathione (GSH) in the brain, the relationship between the concentrations of tissue GSH and uptake of [99mTc]meso-hexamethyl propyleneamine oxime ([99mTc] meso-HMPAO) or [99mTc]d,l-hexamethyl propyleneamine oxime ([99mTc]d,l-HMPAO) was studied in mice. The uptake of [99mTc]meso-HMPAO in the mouse brain was decreased to 35% of control paralleling the decrease in GSH content by pre-loading of diethyl maleate (DEM), an agent to reduce GSH. In contrast, pre-treatment with DEM scarcely affected the 99mTc-d,l-HMPAO uptake in the brain. The DEM treatment decreased the GSH content in liver, kidney, spleen, fat and lung but did not affect the uptake of [99mTc]meso-HMPAO in those tissues except lung. The images of rat brain acquired with a gamma camera showed a significant reduction of [99mTc]meso-HMPAO uptake by DEM treatment. Technetium-99m-meso-HMPAO may be a potential tool to assess GSH content and to estimate antioxidative ability in the brain.
RADIOISOTOPES
A growth hormone deficiency is associated with increases in body fat. However, it currently remai... more A growth hormone deficiency is associated with increases in body fat. However, it currently remains unclear whether subcutaneous-or/and intra-abdominal adipose tissues are markedly elevated in dwarf obesity. Experiments were conducted on the spontaneous dwarf rats (SDRs) and normal Sprague-Dawley (SD) rats using an X-ray computed tomography scanner to determine body composition. A longitudinal study of aging was also conducted to track age-related changes in body composition using same animals. We succeeded to estimate the subcutaneous and intra-abdominal adipose tissue mass in rat by X-ray CT. SDRs demonstrated the dwarf obesity, but SDs did not. SDRs developed dwarf obesity due to the accumulation of subcutaneous-abdominal adipose tissue, but not intra-abdominal adipose tissue. Age-dependent increases in the abdominal adipose tissue were observed in both SDRs and SDs. However, age-dependent increases in intra-abdominal adipose tissue were greater than in subcutaneous-abdominal adipose tissue.
Eur J Nucl Med, 1986
The relationship between 67Ga uptake and heparan sulfate (HS) content in Ehrlich solid tumor (EST... more The relationship between 67Ga uptake and heparan sulfate (HS) content in Ehrlich solid tumor (EST) of mice was investigated, and the effect of cyanomethylamine, papain, streptozotocin, or bleomycin pretreatment on 67Ga uptake in EST was studied. 67Ga uptakes in EST and kidney were much higher than other tissues, and these tissues also contained large amounts of HS. 67Ga uptakes and HS synthesis in the EST were inhibited by pretreatment with cyanomethylamine or papain (inhibitors of fibrosis). Parallel reductions of 67Ga uptake and HS synthesis in EST were observed in EST transplanted into streptozotocin-induced diabetic mice. The weight of EST in the bleomycin-injected group was decreased to less than half of the control, but no effect was observed on 67Ga uptake per gram of EST. These results suggest that 67Ga uptake in the tumor and inflammatory lesions are related to the quantity of HS in these tissues, and the correlation between the uptake of 67Ga and the rate of cellular proliferation is secondary.
Annals of Nuclear Medicine, Jun 1, 2008
K 1 of 11 C-SA4503 correlated with rCBF, but the other three rate constant parameters and BP did ... more K 1 of 11 C-SA4503 correlated with rCBF, but the other three rate constant parameters and BP did not. The regional difference in the BP of 11 C-SA4503 is compatible with those of sigma 1 receptors. In conclusion, successive PET measurements of rCBF and the brain kinetics of radioligand-neuroreceptor binding are useful for the fi rst clinical trial of a newly developed radioligand for mapping neuroreceptors, and the protocol is applicable to pathophysiological studies of brain disorders.
Ann Nucl Med, 2003
We report the first clinical PET study using [1-methyl-11 C]8-dicyclopropylmethyl-1-methyl-3propy... more We report the first clinical PET study using [1-methyl-11 C]8-dicyclopropylmethyl-1-methyl-3propylxanthine ([ 11 C]MPDX) for imaging adenosine A1 receptors in the human brain. The binding of [ 11 C]MPDX evaluated quantitatively as the distribution volume by a graphical analysis was high in the striatum and thalamus, and low in the cerebellum. The distribution pattern of [ 11 C]MPDX was coincident with that of adenosine A1 receptors in vitro reported previously, and was different from those of blood flow and [ 18 F]FDG. The [ 11 C]MPDX PET has the potential for mapping adenosine A1 receptors in the human brain.
Journal of Nuclear Medicine, Oct 1, 1996
To visualize the regional localization of glutathione (GSH) in the brain, the relationship betwee... more To visualize the regional localization of glutathione (GSH) in the brain, the relationship between the concentrations of tissue GSH and uptake of [""Tcyneso-hexamethyl propyleneamine oxime ([""Te] meso-HMPAO) or [99nrTc]d,/-hexamethyl propyleneamine oxime ([""TcJoV-HMPAO) was studied in mice. Methods: The uptake of [^"TcJmeso-HMPAO in the mouse brain was decreased to 35% of control paralleling the decrease in GSH content by pre-loading of diethyl maléate(DEM), an agent to reduce GSH. in contrast, pre treatment with DEM scarcely affected the ""Tc-oV-HMPAO uptake in the brain. Results: The DEM treatment decreased the GSH content in liver, kidney, spleen, fat and lung but did not affect the uptake of [""^cJmeso-HMPAO in those tissues except lung. The images of rat brain acquired with a gamma camera showed a significant reduction of [""TcJmeso-HMPAO uptake by DEM treat ment. Conclusion: Technetium-99m-meso-HMPAO may be a po tential tool to assess GSH content and to estimate antioxidative ability in the brain.
Ann Nucl Med, 2008
K 1 of 11 C-SA4503 correlated with rCBF, but the other three rate constant parameters and BP did ... more K 1 of 11 C-SA4503 correlated with rCBF, but the other three rate constant parameters and BP did not. The regional difference in the BP of 11 C-SA4503 is compatible with those of sigma 1 receptors. In conclusion, successive PET measurements of rCBF and the brain kinetics of radioligand-neuroreceptor binding are useful for the fi rst clinical trial of a newly developed radioligand for mapping neuroreceptors, and the protocol is applicable to pathophysiological studies of brain disorders.
Eur J Nucl Med, 1984
67Ga incorporation in the mitochondrial-lysosomal (Mt-Ly) fraction of rat liver increased sharply... more 67Ga incorporation in the mitochondrial-lysosomal (Mt-Ly) fraction of rat liver increased sharply from 1 to 24 h after 67Ga IV injection, whereas that in the 105,000 g supernatant fraction decreased sharply from 6 to 48 h. Further, when 14C-labeled heparan sulfate (HS: biosynthesized by injection of [1-14C] glucosamine into a rat) was injected intravenously into a rat treated with Triton WR-1339, and the liver was isolated and fractionated, the radioactivity of 14C was concentrated in the lysosomal fraction. The effect of HS on 67Ga uptake in normal rat liver was also studied. On administration of 67Ga-HS complex, the peak uptake of administered radioactivity of 67Ga in rat liver occurred sooner than after the injection of 67Ga alone. The change was greatest in the Mt-Ly fraction among the subcellular fractions. Moreover, the 67Ga uptake in rat liver increased with increasing doses of HS. These results suggest that administered 67Ga may be bound to HS and that the concentration of 67Ga in lysosomes may be related to the in vivo metabolism of HS.
Ann Nucl Med, 2000
Accumulation of [i IC]flumazenil (FMZ) reflects central nervous system benzodiazepine receptor (B... more Accumulation of [i IC]flumazenil (FMZ) reflects central nervous system benzodiazepine receptor (BZR). We searched for the optimal time for a static PET scan with FMZ as semi-quantitative imaging of BZR distribution. In 10 normal subjects, a dynamic series of decay-corrected PET scans was performed for 60 minutes, and the arterial blood was sampled during the scan to measure radioactivity and labeled metabolites. We generated 13 kinds of "static scan" images from the dynamic scan in each subject, and analyzed the pixel correlation for these images versus distribution volume (DV) images. We also analyzed the time for the [l 1C]FM Z in plasma and tissue to reach the equilibrium. The intra-subject pixel correlation demonstrated that the "static scan" images for the period centering around 30 minutes post-injection had the strongest linear correlation with the DV image. The ratio of radioactivity in the cortex to that in the plasma reached a peak at 40 minutes after injection. Considering the physical decay and patient burden, we conclude that the decay corrected static scan for [l tC]FM Z PET as semi-quantitative imaging of BZR distribution is to be optimally acquired from 20 to 40 minutes after injection.
Nucl Med Biol, 2005
We examined the densities of adenosine A2A receptors in cardiac and skeletal muscles between untr... more We examined the densities of adenosine A2A receptors in cardiac and skeletal muscles between untrained and endurance-trained subjects using positron emission tomography (PET) and [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX), a newly developed radioligand for mapping adenosine A2A receptors. Five untrained and five endurance-trained subjects participated in this study. The density of adenosine A2A receptors was evaluated as the distribution volume of [11C]TMSX in
Cancer Research, Jan 15, 1994
Tumor imaging with labeled liposomes is slow; although they reach the tumor quickly, their blood ... more Tumor imaging with labeled liposomes is slow; although they reach the tumor quickly, their blood clearance is slow, and the high blood background hinders early imaging. We have developed a rapid tumor imaging technique based on the active removal of liposomes from the circulation by using the avidin-biotin system. 67Ga-or lnIn-labeled liposomes with biotin molecules bound on the surface were administered to mice bearing sarcoma 180, and avidin was administered 2 h later. The strong affinity between biotin and avidin initiated the aggregation of liposomes, resulting in their rapid removal from the circulation by the reticuloendotheliai system, and the blood level of radioactivity was dramatically reduced without any change of the tumor level. Consequently, the tumor:blood ratio reached 14-18 only 2.5 h after liposome injection. Increased accumulation in the liver was also observed. By this method, an acceptable tumor image could be obtained no more than 2 h after administration of labeled liposomes.
Ann Nucl Med, 2008
Methods We studied fi ve AD patients and seven elderly volunteers. A dynamic series of decay-corr... more Methods We studied fi ve AD patients and seven elderly volunteers. A dynamic series of decay-corrected PET data acquisition was performed for 90 min starting at the time of the injection of 500 MBq of [ 11 C]SA4503. A twotissue three-compartment model was used to estimate K 1 , k 2 , k 3 , k 4 , and the delay between metabolite-corrected plasma and tissue time activity using a Gauss-Newton algorithm. The ratio of k 3 to k 4 was computed as the binding potential (BP), which is linearly related to the density of sigma 1 receptors. Unpaired t tests were used to compare K 1 and BP in patients with AD and normal subjects. Results As compared with normals, BP in the AD was signifi cantly lower in the frontal, temporal, and occipital lobe, cerebellum and thalamus, whereas K 1 was significantly lower in the parietal lobe. Conclusions [ 11 C]SA4503 PET can demonstrate that the density of cerebral and cerebellar sigma 1 receptors is reduced in early AD.
y-glutamylcysteine synthetase. In an in vitro study, ""Tc-HMPAO showed reactivity to th... more y-glutamylcysteine synthetase. In an in vitro study, ""Tc-HMPAO showed reactivity to the molecules possessing a -SH group, but were not specific to GSH. The order of 99rTTc-meso-HMPAOreac tivity to the mouse brain homogenate agreed with the order of GSH concentration: normal > BSO > DEM. GSH was a major contribu tor to the conversion reaction of ""Tc-meso-HMPAO to hydrophilic complex
Oxidative medicine and cellular longevity, 2015
Oxidative stress is believed to greatly contribute to the pathogenesis of various diseases, inclu... more Oxidative stress is believed to greatly contribute to the pathogenesis of various diseases, including neurodegeneration. Impairment of mitochondrial energy production and increased mitochondrial oxidative damage are considered early pathological events that lead to neurodegeneration. Manganese superoxide dismutase (Mn-SOD, SOD2) is a mitochondrial antioxidant enzyme that converts toxic superoxide to hydrogen peroxide. To investigate the pathological role of mitochondrial oxidative stress in the central nervous system, we generated brain-specific SOD2-deficient mice (B-Sod2 (-/-)) using nestin-Cre-loxp system. B-Sod2 (-/-) showed perinatal death, along with severe growth retardation. Interestingly, these mice exhibited spongiform neurodegeneration in motor cortex, hippocampus, and brainstem, accompanied by gliosis. In addition, the mutant mice had markedly decreased mitochondrial complex II activity, but not complex I or IV, in the brain based on enzyme histochemistry. Furthermore, b...
ANTI-AGING MEDICINE, 2011
Objective: We previously found that green tea catechins (GT-catechin) decrease oxidative damage t... more Objective: We previously found that green tea catechins (GT-catechin) decrease oxidative damage to DNA and suppress brain dysfunction in aged senescence-accelerated mice (SAMP10). To clarify the effect of GT-catechin on suppression of brain dysfunction, we compare the effect on learning ability among several catechins and examined the essential intake period for prevention of brain dysfunction. Methods: Male SAMP10 mice were allowed free access to water containing epigallocatechin gallate (EGCG, 0.06 mg/ml), epigallocatechin (EGC, 0.03 mg/ml), GT-catechin (0.2 mg/ml), or green tea extract (0.66 mg/ml). Learning ability of mice was measured using a step-through passive avoidance task. Results: SAMP10 mice exhibit brain dysfunction with aging. However, learning ability was significantly higher in mice that drank GT-catechin and EGCG than same-aged control mice that drank water. EGCG was an important component, but EGC had no effect on learning ability. The learning ability was significantly improved in mice that ingested EGCG for >5 months, and tended to improve in mice that ingested EGCG for 2 or 3 months. Next, the level of synaptophysin, a marker of presynapse, tended to be higher in mice that ingested EGCG but not in mice that ingested EGC. The levels of synaptophysin were significantly higher in mice ingested GT-catechin and green tea extract than control mice. Conclusion: The intake of EGCG, the major catechin in green tea, but not EGC, suppressed age-related brain dysfunction. The effective intake period of EGCG was > 5 months for suppression of brain dysfunction.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1998
The aim of this study was to explain the contribution of mitochondria to the accumulation of 99mT... more The aim of this study was to explain the contribution of mitochondria to the accumulation of 99mTc-meso-hexamethyl propyleneamine oxime (HMPAO) in the brain, after examinations were performed. We studied subcellular distribution of 99mTc-meso-HMPAO and glutathione (GSH) in normal and diethyl maleate (DEM)-administered mice. In normal brain, major radioactivity was found in the mitochondrial (49.0%) and cytosolic fractions (33.0%), while the GSH content was high in the cytosol (63.2%) and mitochondria (30.6%). The radioactivity in mitochondrial, cytosolic, microsomal and nuclear fractions was decreased in a dose-dependent manner by DEM, a GSH depleting agent, to 32.2% (mitochondrial) and 24.7% (cytosolic) of the control by a dose of 550 mg/kg. The GSH content in mitochondrial and cytosolic fractions also decreased in a dose-dependent manner on DEM treatment to 29.3% (mitochondrial) and 30.0% (cytosolic) of the control by 550 mg/kg of DEM. A good correlation was found between the upta...
International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology, 1992
Various radionuclide-ligand complexes were encapsulated in liposomes and their accumulations in t... more Various radionuclide-ligand complexes were encapsulated in liposomes and their accumulations in tumors were studied. Increased tumor accumulation was observed with every complex in the liposome-encapsulated form. However, different accumulation levels were registered for the various radionuclides even though they were all delivered using a similar liposome formulation. Though the liposomes remained intact in the circulation, they were degraded in the tumor, liver and spleen eventually. Thus, this suggests that tumor accumulation of liposome-encapsulated radionuclides is dependent on not only the in vivo behavior of the liposomes themselves, but also the characteristics of nuclide-ligand complexes after their release from liposomes. A correct choice of radionuclides and ligands for encapsulation in liposomes would enable excellent tumor-imaging agents to be achieved.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1999
The relationship between distribution of 99mTc meso-hexamethyl propyleneamine oxime (HMPAO) and g... more The relationship between distribution of 99mTc meso-hexamethyl propyleneamine oxime (HMPAO) and glutathione (GSH) content was studied in the mouse. The regional distributions of 99mTc meso-HMPAO and 99mTc d,I-HMPAO were examined using tissue sampling and autoradiographic methods and were compared with GSH content and distribution by a histochemical procedure. The uptake of 99mTc meso-HMPAO was highest in the cerebellum and lowest in the brain stem, whereas the distribution of 99mTc d,I-HMPAO was more uniform. The regional distribution of 99mTc meso-HMPAO in the mouse brain correlated with GSH content (r = 0.787), but that of 99mTc d,I-HMPAO did not. Treatment with diethyl maleate, a GSH depletor, significantly decreased the 99mTc meso-HMPAO uptake to 21%-33% of the control in every region, but the reduction of the 99mTc d,I-HMPAO uptake was moderate (58%-65% of the control). In the autoradiograph, the radioactivity of 99mTc meso-HMPAO was higher in the gray matter than in the white ...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1997
To clarify whether the content of glutathione (GSH) in the brain can be estimated by the uptake o... more To clarify whether the content of glutathione (GSH) in the brain can be estimated by the uptake of 99mTc-meso-HMPAO, we conducted the following in vivo and in vitro experiments. We investigated the effect of diethyl maleate (DEM) and buthionine sulfoximine (BSO) administration on the brain uptake of 99mTc-meso-HMPAO in the mouse, rat and rabbit, and the chemical specificity of in vitro interaction of 99mTc-HMPAO to GSH using measurements of octanol-extractable radioactivity as an index of remaining intact tracer. The uptake of 99mTc-meso-HMPAO in the mouse and rat brain were reduced together with decreased content of GSH by preloading of DEM, a GSH depletor that acts through glutathione S-transferase. Neither 99mTc-meso-HMPAO uptake nor GSH content was affected in the rabbit brain. Similarly, the uptake of 99mTc-meso-HMPAO and GSH content in the mouse brain was reduced by preinjection of BSO, a GSH depletor that acts through gamma-glutamylcysteine synthetase. In an in vitro study, 9...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1996
To visualize the regional localization of glutathione (GSH) in the brain, the relationship betwee... more To visualize the regional localization of glutathione (GSH) in the brain, the relationship between the concentrations of tissue GSH and uptake of [99mTc]meso-hexamethyl propyleneamine oxime ([99mTc] meso-HMPAO) or [99mTc]d,l-hexamethyl propyleneamine oxime ([99mTc]d,l-HMPAO) was studied in mice. The uptake of [99mTc]meso-HMPAO in the mouse brain was decreased to 35% of control paralleling the decrease in GSH content by pre-loading of diethyl maleate (DEM), an agent to reduce GSH. In contrast, pre-treatment with DEM scarcely affected the 99mTc-d,l-HMPAO uptake in the brain. The DEM treatment decreased the GSH content in liver, kidney, spleen, fat and lung but did not affect the uptake of [99mTc]meso-HMPAO in those tissues except lung. The images of rat brain acquired with a gamma camera showed a significant reduction of [99mTc]meso-HMPAO uptake by DEM treatment. Technetium-99m-meso-HMPAO may be a potential tool to assess GSH content and to estimate antioxidative ability in the brain.