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K Ishiwata

Publications and source records attributed to K Ishiwata.

At least 73 records · Page 4Linked to original sources
PubMed1998

Evaluation of carbon-11-labeled KF17837: a potential CNS adenosine A2a receptor ligand.

UNLABELLED: The 11C-labeled KF17837 ([7-methyl-11C](E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxa nthine) was evaluated as a PET ligand for mapping adenosine A2a receptors in the central nervous system (CNS). METHODS: The regional brain distribution of [11C]KF17837 and the effect of adenosine antagonists on the distribution were measured in mice by the tissue sampling method. In rats, the regional brain uptake of [11C]KF17837 and the effect of carrier KF17837 was visualized by autoradiography. Imaging of the monkey brain with [11C]KF17837 was performed by PET. RESULTS: In mice, a high uptake of [11C]KF17837 was found in the striatum in which A2a receptors were highly enriched. The uptake was decreased by co-injection of carrier KF17837 or a xanthine-type A2a antagonist CSC but not by nonxanthine-type A2a antagonists ZM 241385 or SCH 58261, or an A1 antagonist KF15372. In the rat brain, [11C]KF17837 was accumulated higher in the striatum than in other brain regions, and the uptake was blocked by co-injection of carrier KF17837. In a monkey PET study, a high striatal uptake of radioactivity was observed. CONCLUSION: Carbon-11-KF17837 binds to adenosine A2a receptors in the striatum. However, the presence of an unknown but specific binding site for xanthine-type compounds also was suggested in the other brain regions. The results also suggested that the in vivo receptor-binding sites of xanthine-type ligands are slightly different from those of nonxanthine-type A2a antagonists.

Animals↗
PubMed1997

Effects of reserpine treatment on the dopamine receptor binding of [3H/11C]nemonapride in the mouse and rat brain.

We investigated the effect of reserpine treatment on the striatal uptake of a radiolabeled dopamine D2-like receptor ligand nemonapride (NEM). In mice, the uptake of the [3H]NEM in the striatum, cortex and cerebellum was enhanced by the reserpine pretreatment. Neither the ratio of striatum to cerebellum nor that to cortex was affected by the reserpine pretreatment. In rats, ex vivo autoradiography showed no effect of the reserpine treatment on the striatal uptake of [11C]NEM or the striatum to cortex ratio. The results suggest that the receptor binding of NEM was not significantly influenced by reserpine-induced depletion of endogenous dopamine probably because of its high affinity for the receptors.

Animals↗
PubMed1997

Myocardial adenosine A2a receptor imaging of rabbit by PET with [11C]KF17837.

Adenosine A2a receptors are found in the endothelia, vascular smooth muscle cells and cardiac myocytes. The properties of a carbon-11 labeled A2a antagonist [11C]KF17837 ([7-methyl-11C](E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methy lxa nthine) for myocardial imaging were evaluated by dynamic PET scanning of the myocardium in rabbits. Myocardial uptake of [11C]KF17837 was clearly visualized by PET. The tracer was taken up at a high level by the myocardium immediately after the injection, and the myocardial level of radioactivity gradually decreased. On the other hand, an inactive [11C]Z-isomer of [11C]KF17837 showed a very low myocardial uptake and the myocardium was not visualized with a selective A1 antagonist [11C]KF15372. By co-injection with carrier KF17837 or a xanthine type A2a antagonist 7-chlorostyrylcaffeine (CSC), the myocardial uptake of [11C]KF17837 was completely blocked. The effect of non-xanthine A2a antagonists ZM 241,385 and SCH 58,261, which have a higher affinity than CSC, was smaller than that of the CSC. The effect of weak antagonists caffeine and alloxazine or a xanthine type A1 antagonist KF15372 on the radioactivity level was small. It is concluded that PET with [11C]KF17837 can image myocardial adenosine A2a receptors.

Animals↗
PubMed1997

Carbon-11 labeled ethionine and propionine as tumor detecting agents.

To develop 18F-fluoroalkyl derivatives of methionine (MET) as a tumor detecting agent by mean of clinical PET, a pilot study assessing the potential of their parent compounds, 11C-labeled ethionine (11C-ETH) and propionine (11C-PRO), was performed. 11C-ETH and 11C-PRO were prepared by the reaction of L-homocysteine thiolactone and corresponding 11C-alkyl iodides. After i.v. injection of a mixture of 3H-MET. 14C-ETH and 11C-PRO into mice bearing FM3A mammary carcinoma, the highest FM3A uptake was found in 14C-ETH, followed by 3H-MET and 11C-PRO, while the FM3A-to-brain and FM3A-to-muscle ratios were nearly the same for all three compounds. The FM3A uptake of 14C-ETH and 11C-PRO were nearly equal or slightly higher than the liver uptake. In the pancreas, liver, FM3A and brain tissues, incorporation of 14C-ETH into acid-precipitable materials was much lower than that of 3H-MET, whereas no incorporation of 11C-PRO was found. Brain uptake of all three compounds was significantly reduced by carrier MET-loading (5 min p.i.) or by cycloheximide treatment to inhibit protein synthesis (60 min p.i.), whereas the FM3A uptake was not affected. Incorporation of 14C-ETH into acid-precipitable materials was inhibited by the cycloheximide. The results suggest that 11C-labeled ETH has a similar potential for tumor detection by PET as 11C-MET, and that 11C-PRO has similar properties to those of other artificial amino acids. The development of 18F-fluoroalkyl derivatives of MET is of interest as the next step.

Animals↗
PubMed1997

A stereotaxic method of anatomical localization by means of H(2)15O positron emission tomography applicable to the brain activation study in cats: registration of images of cerebral blood flow to brain atlas.

In the neuronal activation study of normal animals, precise anatomical correlation, preferentially to a detailed brain atlas, is required for the activation foci co-registration. To obtain precise regional correlation between H(2)15O-PET images and the brain atlas, a method of stereotaxic image reorientation was applied to an activation study with vibrotactile stimulation. Cats anesthetized with halothane underwent repeated measurements of regional cerebral blood flow (rCBF) in the resting condition and during vibration of the right forepaw. The image set was adjusted three-dimensionally to the atlas. The postmortem brain was sectioned according to the atlas planes. The activated areas were determined by the stimulus-minus-resting subtraction images, and the areas were projected to the atlas. The PET images of the cat brain were compatible both to the postmortem brain slices and to the brain atlas. The activation foci obtained from the subtraction images corresponded to the area around the coronal sulcus, which is electrophysiologically known as the primary sensory area as described in the atlas. There were precise regional correlations between the PET image and anatomy in a PET activation study of the cat by means of stereotaxic image reorientation.

Animals↗
PubMed1997

Evaluation of carbon-11 labeled KF15372 and its ethyl and methyl derivatives as a potential CNS adenosine A1 receptor ligand.

We prepared [11C]KF15372 ([1-propyl-11C]8-dicyclopropylmethyl-1,3-dipropylxanthine, refs 10, 13) as well as its 11C-ethyl and 11C-methyl derivatives ([11C]EPDX and [11C]MPDX), and examined the potential of the three compounds as PET ligands for CNS adenosine A1 receptors. The three compounds had high affinity for the A1 receptors in vitro in the following order; [11C]EPDX > [11C]KF15372 > [11C]MPDX. In mice, the highest initial brain uptake was found in [11C]MPDX followed by [11C]EPDX and [11C]KF15372, but the level of [11C]MPDX decreased faster than those of the other two compounds. The uptake of each compound was decreased by carrier KF15372, but not by an A2A antagonist, indicating the selective affinity for the A1 receptors. Autoradiography with [11C]MPDX ex vivo demonstrated decreased A1 receptor binding in the superior colliculus of rats deprived of retino-collicular fibers by contralateral eye enucleation. These results show that three compounds have potential as PET ligands for CNS adenosine A1 receptors.

Animals↗
PubMed1997

Gnathostomiasis in frog-eating snakes from Japan.

Gnathostoma doloresi parasitizes the gastric wall of wild (boars) and domestic (pigs) swine (Sus scrofa). Its larvae cause cutaneous larva migrans in humans. Amphibians, reptiles and a freshwater fish are infected with the advanced 3rd stage larvae. Prevalence of G. doloresi larvae were surveyed in several snakes, especially in a common frog-eating snake (Rhabdophis tigrinus). All species of snakes examined were infected with G. doloresi larvae suggesting that snakes are important reservoir hosts. Prevalence of G. doloresi larvae in frog-eating snakes was lower than that found in mammal-eating snakes. Thus, as a source of infection to snakes, small mammals may be more important than frogs in the natural life cycle of G. doloresi in Japan.

Animals↗
PubMed1997

Three-dimensional imaging of cortical structure, function and glioma for tumor resection.

UNLABELLED: A three-dimensional brain imaging protocol with PET and MRI was used to visualize the cortical structure in relation to brain function and glioma infiltration to determine tumor resectability. METHODS: Sixteen patients with glioma had a PET scan with 11C-methionine to visualize tumor infiltration. The PET images were co-registered to the patients' own MRI reconstructed to the three-dimensional brain surface images to indicate the gyral structure and the extent of tumor infiltration. Thirteen patients, who bore tumors adjacent to the language or motor cortex, had H2 15O activation study to locate the eloquent cortex. The area of tumor infiltration was superimposed on the brain surface images together with the language and/or motor cortex. RESULTS: When a tumor was located within a single gyrus without influencing surface cortical gyrus pattern, the motor and language areas were identified morphologically by three-dimensional surface image alone. However, when the tumor caused swelling and deformation of cortical structure, functional mapping with H2(15)O activation technique was essential in locating them correctly. In such cases, the combined mapping of the facial motor area with oral movement and the language area with word repetition was the most useful method to identify the parasylvian structure in the dominant hemisphere. Total or near total resection of low-grade glioma in eight patients and the effective decompression of the active part of the malignant glioma in four patients was completed without causing functional neurological deterioration. CONCLUSION: The three-dimensional expression of cortical structure and function combined with PET glioma imaging with 11C-methionine is useful for radical resection of cerebral glioma.

Adult↗
PubMed1996

Evaluation of the brain uptake properties of [1-11C]labeled hexanoate in anesthetized cats by means of positron emission tomography.

Positron emission tomography (PET) was performed on the cat brain to characterize [1-11C]hexanoate and other [1-11C]labeled short and medium-chain fatty acids as a tracer of fatty acid oxidative metabolism. After an intravenous injection the brain uptake of [1-11C]hexanoate reached a peak followed by rapid washout until 2 min (first phase). Subsequently the total brain uptake was again increased and reached to a peak 7-10 min after tracer injection (second phase). The blood radioactivity of unmetabolized [1-11C]hexanoate was rapidly decreased and almost eliminated within the first 2 min, whereas the blood radioactivity of [11C]CO2/HCO3- was gradually increased and reached a peak approximately 5 min after tracer injection. As the effect of circulating [11C]CO2/HCO3- was examined by a bolus intravenous injection of [11C]CO2/HCO3-, the brain uptake of [11C]CO2/HCO3- was rapidly increased right after the injection and changed parallel to the blood level of [11C]CO2/HCO3-. These results suggest that, in contrast to the previous mouse data, the time-activity curve in the cat brain following intravenous injection of [1-11C]hexanoate has a biphasic pattern, the second phase being determined by peripherally originating [11C]CO2/HCO3-, and therefore does not reflect the metabolism of 11C-labeled fatty acid in the brain.

Animals↗
PubMed1996

A brain uptake study of [1-(11)C]hexanoate in the mouse: the effect of hypoxia, starvation and substrate competition.

We evaluated the potential of sodium [1-(11)C]hexanoate (11C-HA) as a radiopharmaceutical with which to assess oxidative metabolism of the brain by PET. 11C-HA, sodium [1-(14)C]acetate and [3H]deoxyglucose were simultaneously injected into mice under control, hypoxic and starving conditions. In the control, the brain uptake of 11C was maximal at 3 min (% ID/g = 2.2-2.5), being twice as high as that of 14C, followed by a gradual clearance. The time-radioactivity curve of 11C was similar to that of 14C. Hypoxia enhanced the brain uptake of 3H, but not of either 11C or 14C. Starvation enhanced the brain uptake of 3H and 11C. The clearance rate of 11C was not significantly affected by either condition. In the control brain at 3 min postinjection of HA, 65% of the total radioactivity was detected as labeled glutamate and glutamine, which was gradually decreased by 47% at 30 min. The brain to blood ratios of 11C-HA at 3 min were significantly reduced by butyrate, hexanoate and octanoate loading but not by that with other monocarboxylic acids or ketone bodies.

Animals↗
PubMed1996

Synthesis and evaluation of 5-HT3 receptor antagonist [11C]KF17643.

For imaging CNS 5-HT3 receptors by PET, a high affinity 5-HT3 receptor ligand, endo-8-methyl-8-azabicyclo[3.2.1]oct-3-yl 2-(n-propyloxy)-4-quinolinecarboxylate (KF17643), have been labeled with 11C. N-Methylation of the desmethyl compound with [11C]methyl iodide followed by HPLC separation produced [11C]KF17643 with the decay-corrected radiochemical yield of 19-28%, the specific activity of 7.5-49 GBq/mumol and the radiochemical purity of > 99% at 35-40 min from EOB. After i.v. injection of [11C]KF17643 into mice, it was taken by the brain at a high level and was stable for metabolism, but no sign for the 5-HT3 receptor selectivity was found in the brain tissues by the tissue sampling and autoradiography, probably because of large non-specific binding. The [11C]KF17643 was not suitable as a PET ligand for mapping the CNS 5-HT3 receptors.

Animals↗
PubMed1996

Synthesis and evaluation of an 18F-labeled dopa prodrug as a PET tracer for studying brain dopamine metabolism.

In the quantitative studies of presynaptic dopamine metabolism by PET with 6-[18F]fluoro-L-dopa (6-[18F]FDOPA), metabolic analysis in the plasma is required to determine the precise input function because of susceptibility of the compound to peripheral metabolism. In this study, we prepared 6-[18F]-fluoro-O-pivaloyl-L-dopa (6-[18F]FPDOPA) as a prodrug of 6-[18F]FDOPA, and evaluated its potential as a PET tracer in mice. If the 6-[18F]FPDOPA is stable peripherally and is hydrolyzed to 6-[18F]FDOPA in the brain tissues, disadvantage of the 6-[18F]FDOPA will be overcome. Compared with the 6-[18F]FDOPA, the initial brain uptake of the 6-[18F]FPDOPA was lower; however, the uptake in the latter become comparable, and the uptake ratios of striatum to other reference regions were larger. Medication of mice with inhibitors of aromatic amino acid decarboxylase and catechol-O-methyl transferase greatly enhanced the striatal uptake of the two compounds. The reduced brain uptake of the compounds by L-phenylalanine-loading suggested transport through the blood-brain barrier by the neutral amino acid transporter. HPLC analysis showed the presence of 6-[18F]FPDOPA, 6-[18F]FDOPA and 6-[18F]fluorodopamine in the striatum; however, 6-[18F]fluoro-3-O-methyl-L-dopa was a predominate metabolite in the brain and plasma as in the case of [18F]FDOPA. Results suggested that 6-[18F]FPDOPA had characteristics as a prodrug of 6-[18F]FDOPA; however, the compound was also labile to metabolic alteration in vivo.

Animals↗
PubMed1996

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↗
PubMed1996

Endogenous interleukin-4, but not interleukin-10, is involved in suppression of host resistance against Listeria monocytogenes infection in interferon-depleted mice.

The production and roles of endogenous interleukin-4 (IL-4) and IL-10 in a sublethal infection with Listeria monocytogenes were studies in normal mice and anti-gamma interferon (IFN-gamma) monoclonal antibody (MAb)-pretreated mice. In normal mice, the expression of mRNAs for IL-4 and IL-10, which was amplified by reverse transcription-PCR, was induced in the spleens and livers either early or late in infection, although the serum IL-4 and IL-10 were not detectable by enzyme-linked immunosorbent assays. In vivo administration of anti-IL-4 MAb showed no effect on antilisterial resistance, whereas anti-IL-10 MAb partially diminished the defense. In anti-IFN-gamma MAb-pretreated mice, a delay in the bacterial elimination from the spleens and livers was observed and high titers of serum IL-4 and IL-10 were induced late in infection. Production of endogenous IL-4 and IL-10 was suppressed in both CD4+ cell-and CD8+ cell depleted mice. The suppression of antilisterial resistance in anti-IFN-gamma MAb-pretreated mice was canceled when anti-IL-4 MAb was injected late in infection, whereas anti-IL-10 MAb showed no effect. These results suggest that the host immune responses were polarized into the T-helper 2 phenotype in anti-IFN-gamma MAb-pretreated mice and that inhibition of host resistance against L. monocytogenes by depletion of IFN-gamma might be attributable to IL-4 produced by T cells polarized into the T-helper 2 phenotype as well as the inhibition of the IFN-gamma effects.

Animals↗
PubMed1996

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↗
PubMed1996

Validation of recalled food intake in the past in a Japanese population.

To evaluate the validity of the recall method in estimating food intake in the distant past, we assessed past and current food intakes by mailed food questionnaires among 80 residents in Gifu, Japan who had answered the same questionnaire 9 years ago. We compared rank correlations and differences between recalled food intake scores and past ones with those between current food intake scores and past ones. We observed higher scores of recalled intake for meat, potatoes and alcohol, and a lower score of recalled intake for cereals than the scores of past intake. We observed increase in food intake scores of soyabean products, dairy products and potatoes and decrease in that of cereals intakes from past to current. The rank correlation coefficients between the recalled and past food intake scores (r = 0.24-0.89) were greater than those between the current and past ones (r = 0.10-0.70) for every food item except for dairy products. After stratification by sex, age and degree of change in body mass index (BMI), the greater correlation between the recalled and past food intake scores remained. These findings suggest that the recall method is more preferable than the current data to estimate food intake in the distant past in Japan.

Diet Surveys↗
PubMed1996

A feasibility study on L-[1-carbon-11]tyrosine and L-[methyl-carbon-11]methionine to assess liver protein synthesis by PET.

UNLABELLED: We studied the potential of L-[1-11C]tyrosine ([1-11C]Tyr) and L-[methyl-11C]methionine ([Me-11C]Met) as tracers for measuring protein synthesis rate (PSR) in the liver by PET and proposed their metabolic models. METHODS: In the liver and plasma of control and cycloheximide-treated mice injected with [1-14C]Tyr and [Me-3H]Met, incorporation of the radioactivity into the acid-soluble fraction and chloroform/methanol-extract (CM), RNA and protein fractions were measured. Data were compared with those from rat studies with 11C-labeled analogs and PET. RESULTS: In mice, liver uptake of [Me-3H]Met was over twice as large as that of [1-14C]Tyr. Similar uptake patterns of the 11C-labeled analogs were found in rats by PET. In the mouse liver at 1 to 6 hr after injection, approximately 69%-73% of the 14C was detected in the protein fraction, whereas approximately 65%-70% of the 3H was in the CM fraction, which reflected phospholipid synthesis. In plasma, the percentages of the protein fractions were approximately 73%-76% for 14C and approximately 36%-46% for 3H. Gel-filtration analysis suggested that 80% of the 14C-labeled plasma proteins was albumin originating from the liver, which corresponds to approximately 25% of the total labeled proteins synthesized in the liver at 6 hr. When protein synthesis was inhibited by cycloheximide, the liver uptake of the [1-14C]Tyr and the protein-incorporation of 14C in the liver and in plasma were decreased dose-dependently. On the other hand, uptake of [Me-3H]Met was significantly enhanced in the liver due to increased incorporation into the CM fraction. CONCLUSION: [1-Carbon-11]Tyr can be used for measuring the PSR in the liver by PET. Liver uptake of [Me-11C]Met mainly reflects phospholipid synthesis through the transmethylation process.

Animals↗