PubMed Health⌕ Search

Biomedical subjects

Y Kuge

Publications and source records attributed to Y Kuge.

At least 37 records · Page 2Linked to original sources
PubMed2000

Biodistribution of 3,4-dihydro-5-[11C]methoxy-1(2H)-isoquinolinone, a potential PET tracer for poly(ADP-ribose) synthetase.

Poly(adenosine diphosphate-ribose) synthetase (PARS) is a nuclear enzyme that is activated by deoxyribonucleic acid (DNA) strand breaks and participates in DNA repair. Excessive PARS activation, however, leads to cell death due to depletion of adenosine triphosphate (ATP). To evaluate whether it is possible to detect excessive activation of PARS with positron emission tomography (PET), we examined the pharmacokinetics of 3,4-dihydro-5-[(11)C]methoxy-1(2H)-isoquinolinone ([(11)C]MIQO), a potent poly(ADP-ribose) synthetase inhibitor, in the brain of rats and monkeys. Although the uptake of [(11)C]MIQO in the brain of normal rats was low, [(11)C]MIQO was rapidly incorporated into and then quickly washed out from the brain. The uptake of the radiotracer in the brain of normal monkeys was also low; however, [(11)C]MIQO gave a distribution image that differed from that of cerebral blood flow obtained by [(15)O]water-PET. No localization of [(11)C]MIQO in the brain of normal monkeys was observed. Low accumulation of some radioactivity was also observed in muscles surrounding the brain of monkeys, but did not seem to interfere with measurement of [(11)C]MIQO uptake in the brain with PET. Thus, detection of [(11)C]MIQO uptake with PET may be useful for detecting PARS activity in ischemic injury.

Animals↗
PubMed2000

[1-11C]Octanoate as a PET tracer for studying ischemic stroke: evaluation in a canine model of thromboembolic stroke with positron emission tomography.

Octanoate is taken up by the brain and converted in astrocytes to glutamine through the TCA cycle after beta-oxidation. Consequently, [1-11C]octanoate might serve as a useful positron emission tomography (PET) probe for studying cerebral oxidative metabolism and/or astroglial functions. The present study attempted to evaluate the utility of using [1-11C]octanoate as a PET tracer for imaging and evaluating the pathophysiology of ischemic stroke. We used a canine model of thromboembolic stroke. Five male beagle dogs were implanted with an indwelling catheter in the left internal carotid artery. A single autologous blood clot was injected into the left internal carotid artery through the catheter. The brain distribution of [1-11C]octanoate and cerebral blood flow (CBF) were determined 24 h after insult using a high resolution PET scanner. Post mortem brain regions unstained with 2,3,5-triphenyltetrazolium chloride (TTC) were defined as infarcts. In the region of an infarct, accumulation of [1-11C]octanoate decreased concurrently with CBF reduction. In contrast, normal accumulation of [1-11C]octanoate was observed in ischemic but vital regions, suggesting that an increased accumulation of [1-11C]octanoate relative to CBF takes place in these regions. In conclusion, [1-11C]octanoate accumulated in ischemic but vital regions, indicating that [1-11C]octanoate is a potentially useful PET tracer for imaging and evaluating the pathophysiology of ischemic stroke.

Animals↗
PubMed2000

The role of fatty acids in cardiac imaging.

Nuclear medicine has progressed in conjunction with the recent growth of molecular medicine. Myocardial energy metabolism has long been investigated in experimental models with the use of Langendorff's method or coronary sinus blood sampling. However, the introduction of a variety of radiopharmaceutical agents has now made possible easy visualization of myocardial energy metabolism in vivo with nuclear medicine techniques.

Animals↗
PubMed1999

[Synthesis of 18F-FDG with FDG MicroLab system: basic studies for clinical application].

We synthesized 18F-FDG by using an automated synthetic apparatus "FDG MicroLab" (GE Medical Systems) which produces 18F-FDG by a solid phase 18F-fluorination. Its quality and reproducibility were evaluated in order to assess feasibility of the apparatus for routine clinical production of 18F-FDG. For 5 consecutive 18F-FDG synthesis, target irradiation was carried out at 15 microA for 60 min. 18F-FDG was obtained in 50 min after EOB with an end-of-synthesis yield of 9.34 +/- 1.06 GBq. Radiochemical yield and radiochemical purity were 47 +/- 3% (decay corrected) and 98.0 +/- 0.5%, respectively. Other several quality control parameters tested conformed with "Standards of Compounds Labeled with Positron Nuclides" (RADIOISOTOPES, 44, 1995). Thus, the automated synthetic apparatus "FDG MicroLab" has proven to stably produce 18F-FDG with high yield and high purity. The apparatus is feasible for routine clinical production of 18F-FDG.

Chemical Phenomena↗
PubMed1999

[Visualization of normal organs in whole-body FDG-PET imaging].

It is important to know FDG accumulation in the normal distributions for interpreting whole-body PET imaging for tumor detection. Twenty-eight normal subjects were studied with whole-body PET imaging and were examined the intensity of FDG uptake in major organs and the factors which caused it's variety. Emission images were acquired and images were reconstructed without attenuation correction. The intensity of FDG uptake was classified into 4 grades visually. No accumulation was found in the thyroid, the esophagus and the spleen. The oral cavity, the liver, the stomach, and the colon were visualized in all subjects. The laryngeal muscle, the cervical muscle, and the heart accumulated FDG with various grade from 1 to 4 grades. No association was found between the intensity of uptake in the organs and volunteer's age. The fasting time was shorter in volunteers whose heart showed "high" grade than those showed less accumulation (p < 0.05). Serum concentration of free fatty acid was significantly lower in them, too (p < 0.05). Various FDG uptake was observed in many organs, especially the laryngeal muscle, the cervical muscle, and the heart. In our study, there was no facter which caused FDG uptake in organs except for the fasting time and the value of free fatty acid in the heart. Such analysis of whole-body FDG distributions in the normal subjects is valuable for tumor detection with FDG-PET.

Adult↗
PubMed1998

Development of step-specific PET tracers for studying fatty acid beta-oxidation: biodistribution of [1-(11)C] octanoate analogs in rats and a cat.

To evaluate the potential of [1-(11)C]-3-(R,S)-methyloctanoate (BMOA), [1-(11)C]-2-octynoate, and [1-(11)C]-2-decynoate as PET tracers for studying particular steps in fatty acid beta-oxidation, we examined the pharmacokinetics of these compounds in rats and a cat. In rats given these compounds, high levels of radioactivity accumulated in the heart, liver, and kidneys, suggesting their potential as tracers for studying beta-oxidation in these tissues. These organs were clearly visible with PET in a cat given BMOA, indicating the utility of BMOA for imaging these organs.

Animals↗
PubMed1998

[Application of a semi-automatic ROI setting system for brain PET images to animal PET studies].

ProASSIST, a semi-automatic ROI (region of interest) setting system for human brain PET images, has been modified for use with the canine brain, and the performance of the obtained system was evaluated by comparing the operational simplicity for ROI setting and the consistency of ROI values obtained with those by a conventional manual procedure. Namely, we created segment maps for the canine brain by making reference to the coronal section atlas of the canine brain by Lim et al., and incorporated them into the ProASSIST system. For the performance test, CBF (cerebral blood flow) and CMRglc (cerebral metabolic rate in glucose) images in dogs with or without focal cerebral ischemia were used. In ProASSIST, brain contours were defined semiautomatically. In the ROI analysis of the test image, manual modification of the contour was necessary in half cases examined (8/16). However, the operation was rather simple so that the operation time per one brain section was significantly shorter than that in the manual operation. The ROI values determined by the system were comparable with those by the manual procedure, confirming the applicability of the system to these animal studies. The use of the system like the present one would also merit the more objective data acquisition for the quantitative ROI analysis, because no manual procedure except for some specifications of the anatomical features is required for ROI setting.

Animals↗
PubMed1997

Positron emission tomography for quantitative determination of glucose metabolism in normal and ischemic brains in rats: an insoluble problem by the Harderian glands.

To examine the reliability of quantitative positron emission tomography studies in the rat (Rat-PET), we assessed the influence of radioactivity accumulated in the Harderian glands on PET CMRglc determination. We measured CMRglc by PET and ex vivo dissection methods by using 2-[18F]fluoro-2-deoxy-D-glucose in rats with and without focal brain ischemia. The CMRglc values obtained by PET, after correcting with recovery coefficients, were higher than those measured by the ex vivo method at rostral slices, and reduction of the CMRglc in the ischemic brain was not demonstrated by PET in the frontal cortex. The radioactivity accumulated in the Harderian glands prevents the quantitative determination of CMRglc using Rat-PET.

Animals↗
PubMed1996

Uptake of radioactive octanoate in astrocytoma cells: basic studies for application of [11C]octanoate as a PET tracer.

Fatty acids are taken up and metabolized in the brain. In vitro uptake experiments on astrocytoma cells were carried out to assess the potential use of [1-11C]octanoate as a positron emission tomography (PET) tracer for astroglial functions. Uptake of [1-14C]octanoate increased in a time-dependent fashion until 60 min after application. The uptake of [1-11C]octanoate showed similar results to that of [1-14C]octanoate until 10 min. As for medium pH, [1-14C]octanoate uptake increased gradually with the decrease in pH. We also examined the effects of glutamate, glucose deprivation and hypoxia on the uptake of octanoate and found that these conditions did not bring about any change in the extent of [1-14C]octanoate uptake. These results show that the octanoate uptake was not influenced by any of several pathological conditions. When the number of astrocytes increases in the area of hypoglycemia or hypoxia near a brain lesion, the amount of octanoate uptake also increases, so this indicates the possibility that 11C-octanoate will detect a brain lesion.

Astrocytoma↗
PubMed1996

[1-11C]octanoate as a potential PET tracer for studying glial functions: PET evaluation in rats and cats.

To evaluate the ability of [1-11C]octanoate as a PET tracer for imaging the brain, we examined its distribution in the brain and surrounding tissues in rats and cats with PET. In rats, owing to the accumulated radioactivity in the harderian glands, clear brain images were not obtained at rostral levels. In cats, the brain was imaged clearly at every level of the coronal brain slices, suggesting the potential of [1-11C]octanoate for imaging the brain.

Animals↗
PubMed1995

Brain uptake and metabolism of [1-11C]octanoate in rats: pharmacokinetic basis for its application as a radiopharmaceutical for studying brain fatty acid metabolism.

The uptake of octanoate in rat brain and its metabolism were investigated by means of intravenously injecting [1-11C] or [1-14C]octanoate as a tracer. The radioactivity in the cerebrum was increased by an injection of [1-11C]octanoate, and reached its peak level (0.33% ID/g) in about 2 to 5 min, and then decreased slowly. The cerebrum-to-blood ratio of the radioactivity increased with time over a period of 30 min. At 30 sec, [1-11C]octanoate that remained unchanged in the cerebrum accounted for only 8% of the total radioactivity, in spite of there being about 90% in the blood. By means of an injection of [1-14C]octanoate, more than 70% of the total radioactivity in the cerebrum was found to be attributable to radiolabeled glutamate and glutamine at each time point measured between 30 sec and 30 min. The results show that [1-11C]octanoate enters rat brain easily and is trapped in the cerebrum, probably in the form of glutamate and glutamine, and the usefulness of [1-11C]octanoate as a radiopharmaceutical for studying brain fatty acid metabolism by positron emission tomography is therefore suggested.

Animals↗
PubMed1995

Antitumor effect of arterial administration of a medium-chain triglyceride solution of an angiogenesis inhibitor, TNP-470, in rabbits bearing VX-2 carcinoma.

Using rabbits bearing VX-2 carcinoma on the inner side of the leg, we examined the antitumor activity of a medium-chain triglyceride (MCT) solution of an angiogenesis inhibitor, TNP-470 (AGM-1470, 6-O-(N-chloroacetylcarbamoyl)-fumagillol), following administration into the femoral artery feeding the tumor. The MCT solution of TNP-470 (1 and 5 mg) strongly suppressed tumor growth following a single intra-arterial (i.a.) injection 2 or 3 weeks after tumor inoculation. Moreover, remarkable regression of well-developed tumors, those 4 weeks after inoculation, was obtained by i.a. injection of the MCT solution containing 20 mg of TNP-470 without any influence on body weight. The antitumor effects were potentiated by coadministration of doxorubicin or mitomycin C (MMC) in the solution or microspheres containing MMC. In a shell-less chorioallantoic membrane (CAM) assay, angiogenesis was inhibited when a droplet of the MCT solution containing 25 micrograms of TNP-470 was placed on the CAM for 2 days, suggesting that the prolonged antitumor effect resulted from the inhibition of tumor neovascularization by sustained drug release from the preparation. These results indicate that i.a. injection of the MCT solution of TNP-470 is promising for treating well-developed tumors.

Animals↗
PubMed1995

Nylon monofilament for intraluminal middle cerebral artery occlusion in rats.

BACKGROUND AND PURPOSE: In rat middle cerebral artery (MCA) occlusion models with an intraluminal nylon monofilament, lesion volume and its reproducibility vary among laboratories. These variations may be caused by differences in the properties of nylon monofilaments. We performed the present study to compare the effects of two different types of 4-0 nylon monofilament on neurological and morphological outcomes in this model. METHODS: We randomly and blindly used two types of 4-0 nylon monofilament (Ethilon, n = 15, and Nitcho, n = 15) to permanently occlude the ostium of the right MCA intraluminally in rats. Neurological outcome and lesion size were compared 24 hours after MCA occlusion between the two groups. The diameter, tensile strength, and extensibility of each filament were measured. RESULTS: Neurological outcome was not different between the groups. The mortality within 24 hours was 13% (2/15) in the Ethilon group and 0% in the Nitcho group. Total lesion volume in the former was 295.9 +/- 97.2 mm3 (mean +/- SD), significantly larger and more reproducible than that in the latter (190.3 +/- 144.7 mm3, P = .026). The Ethilon filament had a significantly larger diameter (Ethilon, 0.193 +/- 0.001 mm; Nitcho, 0.180 +/- 0.001 mm; P < .0001), poorer tensile strength, and better extensibility than the other. CONCLUSIONS: Exact diameter and quality are not always the same among nylon monofilaments, even if they meet the standard for the designation 4-0. The present study indicates that slight differences of filament characteristics significantly affect lesion volume and its reproducibility. This result may explain some conflicting observations in this MCA occlusion model.

Animals↗
PubMed1994

Antitumor activity of a medium-chain triglyceride solution of the angiogenesis inhibitor TNP-470 (AGM-1470) when administered via the hepatic artery to rats bearing Walker 256 carcinosarcoma in the liver.

The antitumor effect of an angiogenesis inhibitor, TNP-470 (AGM-1470, 6-0-(N-chloroacetylcarbamoyl)-fumagillol), administered via the hepatic artery in a medium-chain triglyceride (MCT) solution, in which TNP-470 is very stable, was examined in rats bearing Walker 256 carcinosarcoma in the liver. The MCT solution containing 0.1 mg of TNP-470 completely suppressed tumor growth after a single arterial injection, and the solutions containing 0.5 approximately 5 mg of TNP-470 caused tumor regression function. These antitumor effects lasted for at least 2 weeks. Moreover, the administration of the MCT solution containing 5 mg of TNP-470 also caused remarkable regression of well-developed enlarged tumors 2 weeks after inoculation, indicating potential in the treatment of unresectable hepatic cancer. When the MCT solution containing radiolabeled TNP-470 was injected via the hepatic artery, the initial radioactivity in the tumor was 22 times that in the normal part of the liver and 5.7 times that in the tumor when an aqueous solution of radiolabeled TNP-470 was injected. Also, in the case of the MCT solution, the radioactivity in the tumor was maintained at a relatively high level for over 2 weeks after injection. These results indicate that the remarkable antitumor effect resulted from the selective delivery and prolonged retention of TNP-470 at the tumor site.

Alanine Transaminase↗
PubMed1993

Enzymatic optical resolution of dibenzoxepins and its application to an optically active antiallergic agent with thromboxane A2 receptor antagonistic activity.

Methyl (+/-)-11-(2-hydroxyethyl)thio-6,11-dihydrodibenz[b,e]oxepin- 2- carboxylate (5) was enantio-selectively acylated with acetic anhydride in an organic medium by Lipase Amano P to give methyl (-)-11-(2-acetoxyethyl)thio-6,11-dihydrodibenz[b,e]oxepin-2- carboxylate (8), and the (+)-enantiomer by Lipase Sigma Type VII. Using Lipase Amano P, (+)- and (-)-(5) could be prepared with high optical purity (84-94% e.e.). These products were respectively converted to (+)- and (-)-KW-4099, which had antiallergic activity with complete retention of the optical purity.

Acylation↗
PubMed1992

Accumulation of radioactivity in the pancreas after intravenous administration of [13N]ammonia.

A biodistribution study of [13N]ammonia in rats showed a high accumulation of radioactivity in the pancreas soon after the intravenous injection of this tracer. In humans, the pancreas was also clearly visualized by dynamic positron emission tomography soon after the intravenous injection of [13N]ammonia. To investigate the mechanism of the pancreatic accumulation of [13N]ammonia, in vitro studies with pancreatic slices and in vivo biodistribution and metabolism studies were carried out in rats. The results indicated that [13N]ammonia enters the pancreas from the blood by diffusion at a rate dependent on local blood flow, and then is rapidly incorporated into the amino acid fraction (mainly the glutamine fraction), followed by its incorporation into protein. These findings suggest that [13N]ammonia could be useful for diagnostic imaging of the pancreas.

Ammonia↗
PubMed1992

Investigation of radiopharmaceuticals for pancreatic imaging: accumulation of amines in the pancreas.

To develop radiopharmaceuticals for pancreatic imaging, radioiodinated ethyl benzene derivatives containing various functional groups (amino, carboxyl, and methyl groups) were synthesized and the effects of these functional groups were compared in vitro and in vivo. At 2 min after intravenous injection, the amino derivative, 2-(4-iodophenyl)-N,N-dimethyl ethylamine, displayed about twice the pancreatic uptake and a more than 8-fold higher pancreas/liver ratio than the carboxyl and methyl derivatives. This high and selective in vivo accumulation on the amino derivative in the pancreas was well supported by in vitro studies on the uptake by pancreatic tissue slices. The mechanism promoting pancreatic accumulation of radiopharmaceuticals with an amino group is also discussed.

Amines↗