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Nagara Tamaki

Publications and source records attributed to Nagara Tamaki.

84 records · Page 5Linked to original sources

In vitro uptake of [1-14C]Octanoate in brain slices of rats: basic studies for assessing [1-11C]Octanoate as a PET tracer of glial functions.

To clarify the contribution of glial cells to octanoate uptake into the brain, we determined the effects of fluoroacetate, a selective inhibitor of glial metabolism, on in vitro brain uptake of [1-14C]octanoate, using rat brain slices. The [1-14C]octanoate uptake significantly decreased, depending on the concentration of fluoroacetate (p = 0.001). The [1-14C]octanoate uptakes at 5 mM (0.23 +/- 0.05% uptake/mg slice) and 25 mM fluoroacetate (0.12 +/- 0.01% uptake/mg slice) were significantly lower than that at control (0.29 +/- 0.02% uptake/mg slice, p < 0.05 and p < 0.001, respectively). The results demonstrate the contribution of glial cells to octanoate uptake into the brain. The potential of [1-11C]octanoate as a PET tracer for studying glial functions is suggested.

Animals↗

A simplified and improved synthesis of [11C]phosgene with iron and iron (III) oxide.

[11C]Phosgene ([11C]COCl2), a useful precursor for labeling several radiopharmaceuticals, is generally produced by catalytic oxidation of [11C]carbon tetrachloride over Fe granules, although in low yields or with poor reproducibility. In order to develop am improved synthesis of [11C]phosgene, two oxidizing agents, Fe2O3 and CuO, were examined. The yield of [11C]phosgene was significantly increased using Fe2O3 powder mixed with Fe granules, while the use of CuO alone, or CuO powder mixed with Fe granules resulted in an insignificant yield. The yield and specific activity of S- (-) [11C]CGP-12177 synthesized using Fe2O3 powder mixed with Fe granules were markedly higher than those synthesized by the previous methods using Fe granules alone or Fe granules mixed with Fe powder. Thus, in the present study, we developed a simple and practical method for the synthesis of [11C]phosgene, which provided an improved yield of S- (-) [11C]CGP-12177.

Carbanilides↗

Age-related changes of myocardial norepinephrine transporter density in rats: implications for differential cardiac accumulation of MIBG in aging.

The myocardial regional distribution of [(125)I]MIBG was examined in various aged (7-, 18-, 42-, 47-, and 65-week-old) rats and compared with the effects of regional myocardial blood flow and norepinephrine transporter (NET) function on regional [(125)I]MIBG accumulation in aged rats. In 7- and 18-week-old rats, the accumulation of [(125)I]MIBG was higher in the inferior wall than anterior wall. However, in more than 42-week-old rats, the uptake of MIBG was lower in the inferior wall than that the anterior wall. The uptake of [(99m)Tc]MIBI was greater in the inferior wall than the anterior wall in 18-week-old rats, but was reduced in the inferior wall compared to the anterior wall in 42- and 47- week-old rats. Furthermore, the in vitro binding studies of [(3)H]desipramine to cardiac membranes showed that the B(max) value of NET was larger for the inferior wall than the anterior wall in 7-week-old rats, but was smaller for the inferior wall than the anterior wall in 47-week-old rats. The K(D) values for both walls were significantly larger in 47-week-old than 7-week-old rats. These results indicated that myocardial MIBG accumulation was lower in the inferior wall than the anterior wall of older rats, and that this differential MIBG accumulation in aging was related to the regional changes in myocardial blood flow and NET functions in the inferior wall.

3-Iodobenzylguanidine↗

Quantitative evaluation of the relative contribution ratio of cerebral tissue to near-infrared signals in the adult human head: a preliminary study.

Combining spatially- and time-resolved spectroscopies. we attempted to quantitatively evaluate the contribution ratio of the partial mean pathlength of cerebral tissue to the observed overall mean pathlength, in which haemoglobin concentrations were selectively changed by administration of acetazolamide. When acetazolamide was administered, the observed increases in oxygenated haemoglobin depended on the probe distance, which became progressively larger at distances of 2, 3 and 4 cm. Increases in oxygen saturation were detected at 3 and 4 cm spacing, but not at 2 cm. Assuming that the modified Lambert-Beer's law can exist in the inhomogeneous structure of the head, then, we could estimate the contribution ratio of the cerebral tissue to optical signals at the probe distances of 2, 3 and 4 cm as 33%, 55% and 69%, respectively. Using these values, we recalculated acetazolamide-induced concentration changes in oxygenated-haemoglobin in the cerebral tissue, which resulted in the same values at distances of 2, 3 and 4 cm as expected. Thus, our present method opened the door to the possibility of selectively obtaining optical signals attributed to cerebral tissue.

Adult↗

Unique profile of spreading depression in a primate model.

Spreading depression (SD) is considered to play a role in pathologic conditions of humans such as in the evolution of ischemic brain injury and migraine aura. Because many studies have demonstrated spreading hypoperfusion in patients with migraine and persistent hypoperfusion in nonprimate animal models of SD, these changes in cerebral blood flow (CBF) were regarded as an epiphenomenon of SD. However, there is no direct evidence of the occurrence of SD in primates. The authors attempted to elicit SD by applying 3.3 mol/L potassium chloride to the cerebral cortex of nine male cynomolgus monkeys. The CBF was monitored by positron emission tomography in five animals. Propagated direct-current shifts were found by the two neighboring microelectrodes only in one animal. The direct-current wave propagated at a speed of 4 mm/min and its amplitude was 20 mV, being consistent with the SD findings. Except in one animal with 6 SD episodes, SD waves were recorded infrequently at the rostral site (none in three animals, once in three, and twice in two). Focal hyperemia accompanied SD. Neither spreading hypoperfusion nor persistent hypoperfusion was found. These unique features of SD in primates raise a doubt as to whether the role of SD in nonprimate animals is the same as that in stroke and migraine in humans.

Animals↗

Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: a study using oxygen 15-labeled water PET.

BACKGROUND: Myocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15-labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD. METHODS AND RESULTS: Twenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF) and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg. kg(-1). min(-1)) were determined with the use of O-15-labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perfusion abnormality (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 +/- 0.54) than in group B (2.22 +/- 0.87, P <.05), in group C (2.92 +/- 1.21, P <.01), and in normal segments (3.86 +/- 1.24, P <.001). CFR in group B was lower than in group C (P <.02) and in normal segments (P <.001). CFR in group C was lower than in normal segments (P <.02). CONCLUSIONS: Areas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments.

Aged↗

Lung tumors evaluated with FDG-PET and dynamic CT: the relationship between vascular density and glucose metabolism.

PURPOSE: The aim of the current study was to evaluate the relationship between FDG-PET and dynamic CT in lung tumors. METHOD: Forty consecutive patients with pulmonary tumors underwent whole-body FDG-PET and contrast-enhanced dynamic CT. The size of tumors was 2.6 +/- 0.2 cm (mean +/- SD) at the largest diameter. The standardized uptake value (SUV) of FDG-PET, peak attenuation (APA), and relative flow (RF) of dynamic CT were evaluated. All patients underwent surgery, and tissue samples were available to be studied. The intratumoral microvessel densities (MVDs) were counted and compared with the radiologic parameters. The duration between radiologic examinations and surgery was within 2 weeks in all patients. RESULTS: The mean SUV, APA, and RF of lung cancers were significantly higher than those of benign lesions (p < 0.05). The mean APA and RF of lung cancers correlated with mean SUV (APA : r = 0.665, p < 0.0001; RF: r = 0.848, p < 0.05) and mean MVD (APA: r = 0.801, p < 0.0001; RF: r = 0.723, p < 0.05). The mean SUV of lung cancers correlated with the mean MVD (r = 0.612, p < 0.001). No correlation was found between the mean APA, RF, SUV, and MVD in benign tumors. CONCLUSION: The APA and RF of dynamic CT correlated with the SUV of FDG-PET imaging in lung cancer. The APA and RF of dynamic CT as an index of blood pooling may be related to increased glucose metabolism in lung cancer.

Adult↗

Positron emission tomography reporter gene imaging in the myocardium: for monitoring of angiogenic gene therapy in ischemic heart disease.

Cardiac angiogenic gene therapy has emerged as a novel treatment approach for patients with intractable ischemic heart disease, aiming at facilitating neovascularization to augment blood flow in the ischemic myocardium by introducing genes encoding for angiogenic factors. While several clinical trials for cardiac angiogenic gene therapy are currently in progress, there remains a discrepancy between impressive preclinical results and their limited clinical findings. On the other hand, positron emission tomography (PET) reporter gene imaging has been developed to monitor expression of transgenes in vivo. PET reporter genes encode for proteins that retain complementary positron-emitting tracers (PET reporter probes), and theoretically any therapeutic gene can be linked and coexpressed with an appropriate PET reporter gene. Consequently, PET reporter gene imaging with a PET reporter probe affords external determination of the location, magnitude, and duration of expression of therapeutic genes noninvasively. Since PET imaging can be performed in various species ranging from mice to humans, in vivo cardiac PET reporter gene imaging could play a critical role in identifying the "missing link" as a powerful translational research tool. In this article, we discuss the role of PET reporter gene imaging in basic and clinical research on cardiac angiogenic gene therapy.

Genes, Reporter↗

Mediastinal lymph node staging by FDG-PET in patients with non-small cell lung cancer: analysis of false-positive FDG-PET findings.

BACKGROUND: Accurate staging of mediastinal and hilar lymph nodes is a critical factor determining operability in patients with non-small cell lung cancer (NSCLC). Positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose as a tracer (FDG-PET) has recently been reported to be more effective in detecting tumor involvement in mediastinal and hilar lymph nodes than computed tomography (CT). OBJECTIVE: In this study, we analyzed the accuracy of FDG-PET in mediastinal and hilar lymph node staging in patients with NSCLC and the factors associated with false-positive or false-negative FDG-PET findings in mediastinal and hilar lymph node staging. METHODS: Fifty-four patients with NSCLC who underwent preoperative analysis including chest CT and whole-body FDG-PET were evaluated retrospectively. Using FDG-PET, lesions were considered to be positive if a definite, localized area of higher uptake, excluding physiologic uptake, than in surrounding normal tissue was present. On CT findings, lymph nodes were considered to be positive if they were >10 mm in short-axis diameter, except subcarinal lymph nodes (#7), which were considered to be positive if they were >15 mm in short-axis diameter. All patients underwent surgical resection of primary tumors and mediastinal and hilar lymph nodes between 1999 and 2001 in our institute. Resected lymph nodes were histologically examined for the existence of tumor cells. RESULTS: A total of 306 lymph nodes were resected and used for analysis. The sensitivity, specificity, positive predictive value and negative predictive value of FDG-PET were 73, 98, 70 and 98%, while those of CT were 55, 96, 55 and 96%, respectively. When pre-operative nodal staging was compared with post-operative histopathological staging, 44 patients (81%) were correctly staged, 7 (13%) were overstaged and 3 (6%) were understaged by FDG-PET, while 39 patients (72%) were correctly staged, 8 (15%) were overstaged and 7 (13%) were understaged by CT. All 7 overstaged patients by FDG-PET had other pulmonary complications, including interstitial pneumonitis (n = 2), previous pulmonary tuberculosis (n = 3), silicosis (n = 1) and emphysema (n = 1), although they were not in the active stage. In 3 understaged patients by FDG-PET, lymph nodes were also undetectable by CT. CONCLUSION: FDG-PET is superior to CT in mediastinal and hilar lymph node staging of patients with NSCLC. However, care should be taken in lymph node staging for patients who have other pulmonary complications, including interstitial pneumonitis, previous pulmonary tuberculosis and silicosis.

Adenocarcinoma↗