SHI Accelerator Service Co.

Shinagawa-ku, Japan

SHI Accelerator Service Co.

Shinagawa-ku, Japan
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PubMed | Okayama University of Science, Medical and Biological Laboratories Co and SHI Accelerator Service Ltd
Type: | Journal: Autoimmunity reviews | Year: 2016

Oxidized LDL (oxLDL) can exist as a complex with An antibody-based PET probe, 3H3-scFv has exhibits specificity towards The present in vivo evidence supports the pathophysiological involvement of oxLDL/


Fujinaga M.,Japan National Institute of Radiological Sciences | Yamasaki T.,Japan National Institute of Radiological Sciences | Yamasaki T.,Tohoku University | Maeda J.,Japan National Institute of Radiological Sciences | And 9 more authors.
Journal of Medicinal Chemistry | Year: 2012

Three novel 4-substituted benzamides have been synthesized as potential ligands for the positron emission tomography (PET) imaging of metabotropic glutamate 1 (mGlu1) receptor in the brain. Of these compounds, N-(4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl)-N,4-dimethylbenzamide (4) exhibited the highest binding affinity (Ki = 13.6 nM) for mGlu1 and was subsequently labeled with carbon-11. In vitro autoradiography using rat brain sections showed that [11C]4 binding was consistent with the distribution of mGlu1, with high specific binding in the cerebellum and thalamus. PET studies with [11C]4 in monkey showed a high brain uptake and a kinetic profile suitable for quantitative analysis. Pretreatment with a mGlu1-selective ligand 16 largely decreased the brain uptake, indicating high in vivo specific binding of [11C]4 to mGlu1. In metabolite analysis, only unchanged [11C]4 was found in the brain. [ 11C]4 is a useful PET ligand for the imaging and quantitative analysis of mGlu1 in monkey brain and merits further evaluation in humans. © 2012 American Chemical Society.


Ogawa M.,Japan National Institute of Radiological Sciences | Ogawa M.,SHI Accelerator Service Ltd. | Takada Y.,Japan National Institute of Radiological Sciences | Takada Y.,Yokohama City University | And 3 more authors.
Nuclear Medicine and Biology | Year: 2010

Introduction: Carbon-11-labeled phosgene is an important labeling precursor for PET molecular probes. Despite the usefulness of [11C]phosgene, some difficulties, especially in the formation of [11C]phosgene process from [11C]CCl4, hamper its use. The present article shows a simple preparation method for [11C]phosgene. Method: [11C]CCl4 was obtained using the conventional method by passing a mixture of [11C]CH4 and Cl2 through a heated quartz tube. The [11C]CCl4 was transformed to [11C]phosgene simply by passing through a pretreatment tube of a Kitagawa gas detection system for the working-environmental CCl4 concentration measurement at room temperature with a flow rate of 50 ml/min. Result: This tube successfully transformed [11C]CCl4 to [11C]phosgene at room temperature. [11C]Phosgene was obtained at nearly 80% radiochemical yield (EOB) in a short synthesis time with high reproducibility. Conclusion: A high yield and reliable [11C]phosgene production method using a gas detector tube system for working-environmental CCl4 concentration measurement was developed. © 2010 Elsevier Inc. All rights reserved.


Takada Y.,Japan National Institute of Radiological Sciences | Takada Y.,Yokohama City University | Ogawa M.,Japan National Institute of Radiological Sciences | Ogawa M.,SHI Accelerator Service Ltd. | And 2 more authors.
Applied Radiation and Isotopes | Year: 2010

Automated radiosynthesis of [2- 11C-carbonyl]dantrolene, the substrate of breast cancer resistance protein (BCRP/ABCG2), was performed for the first time through a multi-step/one-pot labeling sequence that started with ethyl 2-{2-[5-(4-nitrophenyl)furfurylidene]hydrazino}acetate and used [ 11C]phosgene as a labeling agent. After optimization of the automated synthesis conditions and parameters, [2- 11C-carbonyl]dantrolene was obtained at a radiochemical yield of 34.0±8.4% (decay-corrected). The radiochemical purity was greater than 98% and the specific activity was 46.8±15.2GBq/μmol at the end of the synthesis. © 2010 Elsevier Ltd.


Tiwari A.K.,Japan National Institute of Radiological Sciences | Tiwari A.K.,Institute of Nuclear Medicine and Allied Sciences | Yui J.,Japan National Institute of Radiological Sciences | Fujinaga M.,Japan National Institute of Radiological Sciences | And 9 more authors.
Journal of Neurochemistry | Year: 2014

We developed the novel positron emission tomography (PET) ligand 2-[5-(4-[11C]methoxyphenyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl- N-phenylacetamide ([11C]MBMP) for translocator protein (18 kDa, TSPO) imaging and evaluated its efficacy in ischemic rat brains. [11C]MBMP was synthesized by reacting desmethyl precursor (1) with [11C] CH3I in radiochemical purity of ≥ 98% and specific activity of 85 ± 30 GBq/μmol (n = 18) at the end of synthesis. Biodistribution study on mice showed high accumulation of radioactivity in the TSPO-rich organs, e.g., the lungs, heart, kidneys, and adrenal glands. The metabolite analysis in mice brain homogenate showed 80.1 ± 2.7% intact [11C]MBMP at 60 min after injection. To determine the specific binding of [11C]MBMP with TSPO in the brain, in vitro autoradiography and PET studies were performed in an ischemic rat model. In vitro autoradiography indicated significantly increased binding on the ipsilateral side compared with that on the contralateral side of ischemic rat brains. This result was supported firmly by the contrast of radioactivity between the ipsilateral and contralateral sides in PET images. Displacement experiments with unlabelled MBMP or PK11195 minimized the difference in uptake between the two sides. In summary, [11C]MBMP is a potential PET imaging agent for TSPO and, consequently, for the up-regulation of microglia during neuroinflammation. We developed 2-[5-(4-[ 11C]methoxyphenyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl-N- phenylacetamide ([11C]MBMP) as a novel positron emission tomography ligand for imaging of translocator protein (18 kDa, TSPO) in the brain. [ 11C]MBMP exhibited high in vitro and in vivo specific binding with TSPO in the ischemic rat brain. We developed 2-[5-(4-[11C] methoxyphenyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl-N-phenylacetamide ([ 11C]MBMP) as a novel positron emission tomography ligand for imaging of translocator protein (18 kDa, TSPO) in the brain. [11C]MBMP exhibited high in vitro and in vivo specific binding with TSPO in the ischemic rat brain. © 2014 International Society for Neurochemistry.


Yamasaki T.,Japan National Institute of Radiological Sciences | Fujinaga M.,Japan National Institute of Radiological Sciences | Yui J.,Japan National Institute of Radiological Sciences | Ikoma Y.,Japan National Institute of Radiological Sciences | And 7 more authors.
Journal of Cerebral Blood Flow and Metabolism | Year: 2014

Because of its role in multiple central nervous system (CNS) pathways, metabotropic glutamate receptor type 1 (mGluR1) is a crucial target in the development of pharmaceuticals for CNS disorders. N-[4-[6-(isopropylamino)- pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[11C]-methylbenzamide ([11C]ITDM) was recently developed as a positron emission tomography (PET) ligand for mGluR1. To devise a method for measurement of the binding potential (BPND) of [11C]ITDM to mGluR1, reference tissue methods aimed at replacing measurement of the arterial input function are desirable. In this study, we evaluated a noninvasive quantification method of mGluR1 with [11C]ITDM, demonstrating its accuracy using Huntington disease model R6/2 mice. The BPND measurements based on the Logan reference (Logan Ref) method have closely approximated that based on the arterial input method. We performed PET analysis with Logan Ref to assess its accuracy in quantifying the decline of mGluR1 expression in R6/2 mice. Significant decreases in BPND values in R6/2 mice were detected in cerebellum, thalamus, striatum, and cingulate cortex. We compared autoradiographs of R6/2 mouse brain sections with immunohistochemical images, and found a close correlation between changes in radioactive signal intensity and degree of mGluR1 expression. In conclusion, [11C]ITDM-PET is a promising tool for in vivo quantification of mGluR1 expression. © 2014 ISCBFM All rights reserved.


Xie L.,Japan National Institute of Radiological Sciences | Yui J.,Japan National Institute of Radiological Sciences | Hatori A.,Japan National Institute of Radiological Sciences | Yamasaki T.,Japan National Institute of Radiological Sciences | And 7 more authors.
Journal of Hepatology | Year: 2012

Background & Aims: Mitochondrial dysfunction is responsible for liver damage and disease progression in non-alcoholic fatty liver disease (NAFLD). Translocator protein (18 kDa) (TSPO), a mitochondrial transmembrane protein, plays important roles in modulating mitochondrial function. This study explored whether TSPO can be used as an imaging biomarker of non-invasive diagnosis and staging of NAFLD, monitored using positron emission tomography (PET) with a TSPO radioligand [18F]FEDAC. Methods: PET with [18F]FEDAC, non-enhanced computerized tomography (CT), autoradiography, histopathology, and gene analysis were performed to evaluate and quantify TSPO levels and NAFLD progression in methionine and choline-deficient diet-fed mice. Correlations were analyzed between uptake ratio of radioactivity and NAFLD activity score (NAS) in the liver. Results: Uptake of [18F]FEDAC obviously increased with disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH) (p <0.01). A close correlation was identified between [ 18F]FEDAC uptake ratio and NAS in the liver (Pearson's r = 0.922, p = 0.000). Specific binding of [18F]FEDAC to TSPO in the NAFLD livers was assessed in competition studies with the unlabelled TSPO-selective ligand PK11195. Autoradiography and histopathology confirmed the PET imaging results. Further, the mRNA levels of the functional macromolecular signaling complex composed of TSPO were obviously higher compared to controls. Conclusions: TSPO expression increases in NAFLD and closely correlates with NAFLD progression. TSPO as a specific molecular imaging biomarker may open a novel avenue for non-invasive, reliable, and quantitative diagnosis and staging of NAFLD. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


Yui J.,Japan National Institute of Radiological Sciences | Xie L.,Japan National Institute of Radiological Sciences | Fujinaga M.,Japan National Institute of Radiological Sciences | Yamasaki T.,Japan National Institute of Radiological Sciences | And 5 more authors.
Stroke | Year: 2013

Background and Purpose - Recent pharmacological evidence shows that antagonists for the metabotropic glutamate 1 (mGlu1) receptor exhibit neuroprotective effects in an ischemic brain. The aim of this study was to visualize the mGlu1 receptor and to monitor neuroprotective effects in a rat model of mild focal ischemia using positron emission tomography (PET) with N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-[ 11C]methoxy-N-methylbenzamide ([11C]ITMM), a radiotracer for mGlu1. Methods - Rats were subjected to a 30-minute transient right middle cerebral artery occlusion. Saline or minocycline, a neuroprotective agent, was intravenously injected immediately after surgery and then daily during the subsequent 7 days. PET imaging with [11C]ITMM was performed on the rats on days 1 to 7 after ischemia. In vitro autoradiography and histopathologic staining were conducted to confirm the results of in vivo PET. Results - PET with [11C]ITMM demonstrated a gradual decrease of radioactivity in the ipsilateral sides of the ischemic brains. The radioactivity uptake ratio between the ipsilateral and contralateral sides also decreased with time. Minocycline treatment slowed down the decrease in the radioactivity level in the ipsilateral sides. Pretreatment with JNJ16259685, an mGlu1-selective ligand, significantly reduced brain radioactivity, confirming that the uptake of [ 11C]ITMM primarily reflects mGlu1 levels in the brain regions, including the ischemic area. In vitro autoradiography and histopathology confirmed the changes in mGlu1 levels in the brains. Conclusions - [ 11C]ITMM-PET may be a useful technique for characterizing the change in mGlu1 level during the occurrence and progression of neuronal damage and for evaluating the neuroprotective effects of drugs after ischemia. © 2013 American Heart Association, Inc.


Yui J.,Japan National Institute of Radiological Sciences | Maeda J.,Japan National Institute of Radiological Sciences | Kumata K.,Japan National Institute of Radiological Sciences | Kawamura K.,Japan National Institute of Radiological Sciences | And 7 more authors.
Journal of Nuclear Medicine | Year: 2010

We evaluated two 18F-labeled PET ligands, N-benzyl-N-ethyl-2-[7, 8-dihydro-7-(2-18F-fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl] acetamide (18F-FEAC) and N-benzyl-N-methyl-2-[7,8-dihydro-7-(2- 18F-fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide ( 18F-FEDAC), by investigating their kinetics in the monkey brain and by performing in vitro and in vivo imaging of translocator protein (18 kDa) (TSPO) in the infarcted rat brain. Methods: Dissection was used to determine the distribution of 18F-FEAC and 18F-FEDAC in mice, whereas PET was used for a monkey. With each 18F-ligand, in vitro autoradiography and small-animal PET were performed on infarcted rat brains. Results: 18F-FEAC and 18F-FEDAC had a high uptake of radioactivity in the heart, lung, and other TSPO-rich organs of mice. In vitro autoradiography showed that the binding of each 18F-ligand significantly increased on the ipsilateral side of rat brains, compared with the contralateral side. In a small-animal PET study, PET summation images showed the contrast of radioactivity between ipsilateral and contralateral sides. Pretreatment with TSPO ligands N-benzyl-N-ethyl-2-(7-methyl-8-oxo-2-phenyl-7,8- dihydro-9H-purin-9-yl) acetamide (AC-5216) or (R)-N-methyl-N-(1-methylpropyl)-1- (2-chlorophenyl)isoquinoline-3-carboxamide (PK11195) diminished the difference in uptake between the 2 sides. The PET study showed that each 18F-ligand had uptake and distribution patterns in the monkey brain similar to those of 11C-AC-5216. After injection into the monkey during PET, the uptake of each 18F-ligand in the brain decreased over time whereas 11C-AC-5216 did not. In the brain homogenate of mice, the percentage of the fraction corresponding to intact 18F-FEAC and 18F-FEDAC was 68% and 75% at 30 min after injection. In monkey plasma, each 18F-ligand was scarcely metabolized until the end of the PET scan. Conclusion: 18F-FEAC and 18F-FEDAC produced in vitro and in vivo signals allowing visualization of the increase in TSPO expression in the infarcted rat brain. The kinetics of both 18F- ligands in the monkey brain and tolerance for in vivo metabolism suggested their usefulness. for imaging studies of TSPO in primates. Copyright © 2010 by the Society of Nuclear Medicine, Inc.

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