2021/11/12 更新

写真a

ノセ ナオコ
能勢 直子
NOSE Naoko
所属
医歯薬学域 助教(特任)
職名
助教(特任)
外部リンク

学位

  • 博士(保健学) ( 2021年9月   大阪大学 )

研究キーワード

  • 再生医療

  • 分子イメージング

  • 核医学

研究分野

  • ライフサイエンス / 放射線科学

学歴

  • 大阪大学大学院   医学系研究科博士課程   保健学専攻

    2018年4月 - 2021年9月

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  • 大阪教育大学   教育学部   教養学科自然研究専攻生命科学コース

    2002年4月 - 2006年3月

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論文

  • [18F]FDG-labelled stem cell PET imaging in different route of administrations and multiple animal species. 査読 国際共著 国際誌

    Naoko Nose, Suguru Nogami, Kazuhiro Koshino, Xinyu Chen, Rudolf A Werner, Soki Kashima, Steven P Rowe, Constantin Lapa, Kazuki Fukuchi, Takahiro Higuchi

    Scientific reports   11 ( 1 )   10896 - 10896   2021年5月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Stem cell therapy holds great promise for tissue regeneration and cancer treatment, although its efficacy is still inconclusive and requires further understanding and optimization of the procedures. Non-invasive cell tracking can provide an important opportunity to monitor in vivo cell distribution in living subjects. Here, using a combination of positron emission tomography (PET) and in vitro 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) direct cell labelling, the feasibility of engrafted stem cell monitoring was tested in multiple animal species. Human mesenchymal stem cells (MSCs) were incubated with phosphate-buffered saline containing [18F]FDG for in vitro cell radiolabelling. The pre-labelled MSCs were administrated via peripheral vein in a mouse (n = 1), rats (n = 4), rabbits (n = 4) and non-human primates (n = 3), via carotid artery in rats (n = 4) and non-human primates (n = 3), and via intra-myocardial injection in rats (n = 5). PET imaging was started 10 min after cell administration using a dedicated small animal PET system for a mouse and rats. A clinical PET system was used for the imaging of rabbits and non-human primates. After MSC administration via peripheral vein, PET imaging revealed intense radiotracer signal from the lung in all tested animal species including mouse, rat, rabbit, and non-human primate, suggesting administrated MSCs were trapped in the lung tissue. Furthermore, the distribution of the PET signal significantly differed based on the route of cell administration. Administration via carotid artery showed the highest activity in the head, and intra-myocardial injection increased signal from the heart. In vitro [18F]FDG MSC pre-labelling for PET imaging is feasible and allows non-invasive visualization of initial cell distribution after different routes of cell administration in multiple animal models. Those results highlight the potential use of that imaging approach for the understanding and optimization of stem cell therapy in translational research.

    DOI: 10.1038/s41598-021-90383-4

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  • Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay. 査読 国際共著 国際誌

    Nose N, Werner RA, Ueda Y, Günther K, Lapa C, Javadi MS, Fukushima K, Edenhofer F, Higuchi T

    International journal of cardiology   269   229 - 234   2018年10月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.ijcard.2018.06.089

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  • Synthesis and Initial Characterization of a Reversible, Selective 18F-Labeled Radiotracer for Human Butyrylcholinesterase. 査読 国際共著 国際誌

    Christian Gentzsch, Xinyu Chen, Philipp Spatz, Urban Košak, Damijan Knez, Naoko Nose, Stanislav Gobec, Takahiro Higuchi, Michael Decker

    Molecular imaging and biology   23 ( 4 )   505 - 515   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: A neuropathological hallmark of Alzheimer's disease (AD) is the presence of amyloid-β (Aβ) plaques in the brain, which are observed in a significant number of cognitively normal, older adults as well. In AD, butyrylcholinesterase (BChE) becomes associated with Aβ aggregates, making it a promising target for imaging probes to support diagnosis of AD. In this study, we present the synthesis, radiochemistry, in vitro and preliminary ex and in vivo investigations of a selective, reversible BChE inhibitor as PET-tracer for evaluation as an AD diagnostic. PROCEDURES: Radiolabeling of the inhibitor was achieved by fluorination of a respective tosylated precursor using K[18F]. IC50 values of the fluorinated compound were obtained in a colorimetric assay using recombinant, human (h) BChE. Dissociation constants were determined by measuring hBChE activity in the presence of different concentrations of inhibitor. RESULTS: Radiofluorination of the tosylate precursor gave the desired radiotracer in an average radiochemical yield of 20 ± 3 %. Identity and > 95.5 % radiochemical purity were confirmed by HPLC and TLC autoradiography. The inhibitory potency determined in Ellman's assay gave an IC50 value of 118.3 ± 19.6 nM. Dissociation constants measured in kinetic experiments revealed lower affinity of the inhibitor for binding to the acylated enzyme (K2 = 68.0 nM) in comparison to the free enzyme (K1 = 32.9 nM). CONCLUSIONS: The reversibly acting, selective radiotracer is synthetically easily accessible and retains promising activity and binding potential on hBChE. Radiosynthesis with 18F labeling of tosylates was feasible in a reasonable time frame and good radiochemical yield.

    DOI: 10.1007/s11307-021-01584-2

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  • Synthesis and Initial Characterization of a Selective, Pseudo-irreversible Inhibitor of Human Butyrylcholinesterase as PET Tracer. 査読 国際共著 国際誌

    Christian Gentzsch, Matthias Hoffmann, Yasuhiro Ohshima, Naoko Nose, Xinyu Chen, Takahiro Higuchi, Michael Decker

    ChemMedChem   16 ( 9 )   1427 - 1437   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The enzyme butyrylcholinesterase (BChE) represents a promising target for imaging probes to potentially enable early diagnosis of neurodegenerative diseases like Alzheimer's disease (AD) and to monitor disease progression in some forms of cancer. In this study, we present the design, facile synthesis, in vitro and preliminary ex vivo and in vivo evaluation of a morpholine-based, selective inhibitor of human BChE as a positron emission tomography (PET) tracer with a pseudo-irreversible binding mode. We demonstrate a novel protecting group strategy for 18 F radiolabeling of carbamate precursors and show that the inhibitory potency as well as kinetic properties of our unlabeled reference compound were retained in comparison to the parent compound. In particular, the prolonged duration of enzyme inhibition of such a morpholinocarbamate motivated us to design a PET tracer, possibly enabling a precise mapping of BChE distribution.

    DOI: 10.1002/cmdc.202000942

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  • Capabilities of multi-pinhole SPECT with two stationary detectors for in vivo rat imaging 査読 国際共著 国際誌

    Jan P. Janssen, Jan V. Hoffmann, Takayuki Kanno, Naoko Nose, Jan-Peter Grunz, Masahisa Onoguchi, Xinyu Chen, Constantin Lapa, Andreas K. Buck, Takahiro Higuchi

    Scientific Reports   10 ( 1 )   18616 - 18616   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    <title>Abstract</title>
    We aimed to investigate the image quality of the U-SPECT5/CT E-Class a micro single-photon emission computed tomography (SPECT) system with two large stationary detectors for visualization of rat hearts and bones using clinically available <sup>99m</sup>Tc-labelled tracers. Sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR) of the small-animal SPECT scanner were investigated in phantom studies using an ultra-high-resolution rat and mouse multi-pinhole collimator (UHR-RM). Point source, hot-rod, and uniform phantoms with <sup>99m</sup>Tc-solution were scanned for high-count performance assessment and count levels equal to animal scans, respectively. Reconstruction was performed using the similarity-regulated ordered-subsets expectation maximization (SROSEM) algorithm with Gaussian smoothing. Rats were injected with ~ 100 MBq [<sup>99m</sup>Tc]Tc-MIBI or ~ 150 MBq [<sup>99m</sup>Tc]Tc-HMDP and received multi-frame micro-SPECT imaging after tracer distribution. Animal scans were reconstructed for three different acquisition times and post-processed with different sized Gaussian filters. Following reconstruction, CNR was calculated and image quality evaluated by three independent readers on a five-point scale from 1 = “very poor” to 5 = “very good”. Point source sensitivity was 567 cps/MBq and radioactive rods as small as 1.2 mm were resolved with the UHR-RM collimator. Collimator-dependent uniformity was 55.5%. Phantom CNR improved with increasing rod size, filter size and activity concentration. Left ventricle and bone structures were successfully visualized in rat experiments. Image quality was strongly affected by the extent of post-filtering, whereas scan time did not have substantial influence on visual assessment. Good image quality was achieved for resolution range greater than 1.8 mm in bone and 2.8 mm in heart. The recently introduced small animal SPECT system with two stationary detectors and UHR-RM collimator is capable to provide excellent image quality in heart and bone scans in a rat using standardized reconstruction parameters and appropriate post-filtering. However, there are still challenges in achieving maximum system resolution in the sub-millimeter range with in vivo settings under limited injection dose and acquisition time.

    DOI: 10.1038/s41598-020-75696-0

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    その他リンク: http://www.nature.com/articles/s41598-020-75696-0

  • Stability of Distribution of F18 Flurpiridaz After Transient Coronary Occlusion in Pigs. 査読 国際共著 国際誌

    Rudolf A Werner, Kazuhiro Koshino, Kenji Arimitsu, Constantin Lapa, Mehrbod S Javadi, Steven P Rowe, Naoko Nose, Hiroyuki Kimura, Kenji Fukushima, Takahiro Higuchi

    JACC. Cardiovascular imaging   12 ( 11 Pt 1 )   2269 - 2271   2019年11月

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  • Initial Evaluation of AF78: a Rationally Designed Fluorine-18-Labelled PET Radiotracer Targeting Norepinephrine Transporter. 査読 国際共著 国際誌

    Chen X, Fritz A, Werner RA, Nose N, Yagi Y, Kimura H, Rowe SP, Koshino K, Decker M, Higuchi T

    Molecular imaging and biology   22 ( 3 )   602 - 611   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s11307-019-01407-5

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  • Stability of Myocardial F-18-flurpiridazDistribution after Transient Coronary Occlusion in Pigs 査読 国際共著 国際誌

    Werner Rudolf, Koshino Kazuhiro, Arimitsu Kenji, Lapa Constantin, Fukujima Kenji, Rowe Steven, Nose Naoko, Kimura Hiroyuki, Higuchi Takahiro

    JOURNAL OF NUCLEAR MEDICINE   60   2019年5月

  • The Impact of Ageing on 11C-Hydroxyephedrine Uptake in the Rat Heart. 査読 国際共著 国際誌

    Rudolf A Werner, Xinyu Chen, Yoshifumi Maya, Christoph Eissler, Mitsuru Hirano, Naoko Nose, Hiroshi Wakabayashi, Constantin Lapa, Mehrbod S Javadi, Takahiro Higuchi

    Scientific reports   8 ( 1 )   11120 - 11120   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We aimed to explore the impact of ageing on 11C-hydroxyephedrine (11C-HED) uptake in the healthy rat heart in a longitudinal setting. To investigate a potential cold mass effect, the influence of specific activity on cardiac 11C-HED uptake was evaluated: 11C-HED was synthesized by N-methylation of (-)-metaraminol as the free base (radiochemical purity >95%) and a wide range of specific activities (0.2-141.9 GBq/μmol) were prepared. 11C-HED (48.7 ± 9.7MBq, ranged 0.2-60.4 μg/kg cold mass) was injected in healthy Wistar Rats. Dynamic 23-frame PET images were obtained over 30 min. Time activity curves were generated for the blood input function and myocardial tissue. Cardiac 11C-HED retention index (%/min) was calculated as myocardial tissue activity at 20-30 min divided by the integral of the blood activity curves. Additionally, the impact of ageing on myocardial 11C-HED uptake was investigated longitudinally by PET studies at different ages of healthy Wistar Rats. A dose-dependent reduction of cardiac 11C-HED uptake was observed: The estimated retention index as a marker of norepinephrine function decreased at a lower specific activity (higher amount of cold mass). This observed high affinity of 11C-HED to the neural norepinephrine transporter triggered a subsequent study: In a longitudinal setting, the 11C-HED retention index decreased with increasing age. An age-related decline of cardiac sympathetic innervation could be demonstrated. The herein observed cold mass effect might increase in succeeding scans and therefore, 11C-HED microPET studies should be planned with extreme caution if one single radiosynthesis is scheduled for multiple animals.

    DOI: 10.1038/s41598-018-29509-0

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  • The Impact of Ageing on [C-11]meta-Hydroxyephedrine Uptake in the Rat Heart 査読 国際共著 国際誌

    Werner Rudolf, Chen Xinyu, Hirano Mitsuru, Nose Naoko, Lapa Constantin, Javadi Mehrbod, Higuchi Takahiro

    JOURNAL OF NUCLEAR MEDICINE   59   2018年5月

  • Subcellular storage and release mode of the novel 18F-labeled sympathetic nerve PET tracer LMI1195 査読 国際共著 国際誌

    Xinyu Chen, Rudolf A. Werner, Constantin Lapa, Naoko Nose, Mitsuru Hirano, Mehrbod S. Javadi, Simon Robinson, Takahiro Higuchi

    EJNMMI Research   8 ( 1 )   12 - 12   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Verlag  

    Background: 18F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine (18F-LMI1195) is a new class of PET tracer designed for sympathetic nervous imaging of the heart. The favorable image quality with high and specific neural uptake has been previously demonstrated in animals and humans, but intracellular behavior is not yet fully understood. The aim of the present study is to verify whether it is taken up in storage vesicles and released in company with vesicle turnover. Results: Both vesicle-rich (PC12) and vesicle-poor (SK-N-SH) norepinephrine-expressing cell lines were used for in vitro tracer uptake studies. After 2 h of 18F-LMI1195 preloading into both cell lines, effects of stimulants for storage vesicle turnover (high concentration KCl (100 mM) or reserpine treatment) were measured at 10, 20, and 30 min. 131I-meta-iodobenzylguanidine (131I-MIBG) served as a reference. Both high concentration KCl and reserpine enhanced 18F-LMI1195 washout from PC12 cells, while tracer retention remained stable in the SK-N-SH cells. After 30 min of treatment, 18F-LMI1195 releasing index (percentage of tracer released from cells) from vesicle-rich PC12 cells achieved significant differences compared to cells without treatment condition. In contrast, such effect could not be observed using vesicle-poor SK-N-SH cell lines. Similar tracer kinetics after KCl or reserpine treatment were also observed using 131I-MIBG. In case of KCl exposure, Ca2+-free buffer with the calcium chelator, ethylenediaminetetracetic acid (EDTA), could suppress the tracer washout from PC12 cells. This finding is consistent with the tracer release being mediated by Ca2+ influx resulting from membrane depolarization. Conclusions: Analogous to 131I-MIBG, the current in vitro tracer uptake study confirmed that 18F-LMI1195 is also stored in vesicles in PC12 cells and released along with vesicle turnover. Understanding the basic kinetics of 18F-LMI1195 at a subcellular level is important for the design of clinical imaging protocols and imaging interpretation.

    DOI: 10.1186/s13550-018-0365-9

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  • Radionuclide tracer assay for metabolic substrate shift during cardiac differentiation 査読 国際共著 国際誌

    Naoko Nose, Ryohei Kobayashi, Rudolf Werner, Yuichiro Ueda, Constantin Lapa, Kazuhito Fukushima, Takahiro Higuchi

    JOURNAL OF NUCLEAR MEDICINE   58   2017年5月

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    担当区分:筆頭著者   記述言語:英語   出版者・発行元:SOC NUCLEAR MEDICINE INC  

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  • Assessment of coronary flow reserve using a combination of planar first-pass angiography and myocardial SPECT: Comparison with myocardial O-15-water PET 査読 国際共著 国際誌

    Naoko Nose, Kazuhito Fukushima, Constantin Lapa, Rudolf A. Werner, Mehrbod Som Javadi, Junichi Taki, Takahiro Higuchi

    INTERNATIONAL JOURNAL OF CARDIOLOGY   222   209 - 212   2016年11月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    Coronary flow reserve (CFR), defined as the ratio of maximum coronary flow increase from baseline resting blood flow, is one of the most sensitive parameters to detect early signs of coronary arteriosclerosis at the microvascular level. Myocardial perfusion PET is a well-established technology for CFR measurement, however, availability is still limited. The aim of this study is to introduce and validate myocardial flow reserve measurement by myocardial perfusion SPECT.
    Methods: Myocardial perfusion SPECT at rest and ATP stress (0.16 mg/Kg/min) was performed in 10 patients with known coronary artery disease. Immediately after the injection of Tc-99m sestamibi (MIBI), left ventricular (LV) dynamic planar angiographic data were obtained for 90s. Coronary flow reserve index as measured by MIBI SPECT (CFRMIBI) was calculated as follows: CFRMIBI = Cm(s)Sbm(b) / Cm(b)Sbm(s), where subscripts (b, s,) Cm, and Sbm indicate baseline, during stress, myocardial counts with MIBI SPECT, and integral of LV counts with first pass angiography, respectively. Additionally, standard stress/rest O-15-water PET to estimate CFR was performed in all patients as standard of reference.
    Results: CFRMIBI increased in conjunction with CFR, but underestimated blood flow at high flow rates. The relationship between CFRMIBI (Y) and CFRPET (X) was well fitted as follows: Y = 1.40x(1-exp(1.79/x)) (r = 0.84).
    Conclusions: The index of CFRMIBI reflects the CFR by O-15-water PET but underestimates flow at high flows, maybe as a reflection of pharmacokinetic limitations of MIBI. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.ijcard.2016.07.183

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  • Radionuclide functional assay for in vitro metabolic status during cardiac differentiation in human induced pluripotent stem cells 査読 国際共著 国際誌

    Werner Rudolf, Nose Naoko, Kadari Asifiqbal, Lapa Constantin, Javadi Mehrbod, Ueda Yuichiro, Fukushima Kazuhito, Edenhofer Frank, Higuchi Takahiro

    JOURNAL OF NUCLEAR MEDICINE   57   2016年5月

  • Bioactive beads-mediated transformation of rice with large DNA fragments containing Aegilops tauschii genes 査読 国際誌

    Naoki Wada, Shin&apos, ichiro Kajiyama, Yukio Akiyama, Shigeki Kawakami, Daisuke No, Susumu Uchiyama, Motoyasu Otani, Takiko Shimada, Naoko Nose, Go Suzuki, Yasuhiko Mukai, Kiichi Fukui

    PLANT CELL REPORTS   28 ( 5 )   759 - 768   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Transformation with large DNA molecules enables multiple genes to be introduced into plants simultaneously to produce transgenic plants with complex phenotypes. In this study, a large DNA fragment (ca. 100 kb) containing a set of Aegilops tauschii hardness genes was introduced into rice plants using a novel transformation method, called bioactive beads-mediated transformation. Nine transgenic rice plants were obtained and the presence of transgenes in the rice genome was confirmed by PCR and FISH analyses. The results suggested that multiple transgenes were successfully integrated in all transgenic plants. The expression of one of the transgenes, puroindoline b, was confirmed at the mRNA and protein levels in the T(2) generation. Our study clearly demonstrates that the bioactive bead method is capable of producing transgenic rice plants carrying large DNA fragments. This method will facilitate the production of useful transgenic plants by introducing multiple genes simultaneously.

    DOI: 10.1007/s00299-009-0678-2

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共同研究・競争的資金等の研究

  • レポーター蛋白基質特異性を応用した高感度汎用型生体移植後細胞モニタリング法の開発

    研究課題/領域番号:20K16386  2020年04月 - 2022年03月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    能勢 直子

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

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