Development of Cellular and Molecular Magnetic Resonance Imaging and Application using targeted multimodal probes.

• Project/Area Number: 19500401
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biological material science
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: AOKI Ichio National Institute of Radiological Sciences, 分子イメージング研究センター, チームリーダー (10319519)
• Co-Investigator(Kenkyū-buntansha): TANAKA Chuzo 明治国際医療大学, 医学教育研究センター, 教授 (80163541) ; KANNO Iwao 独立行政法人放射線医学総合研究所, 分子イメージング研究センター, センター長 (10360356)
• Co-Investigator(Renkei-kenkyūsha): TANAKA Chuzo 明治国際医療大学, 医学教育研究センター, 教授 (80163541) ; KANNO Iwao 独立行政法人放射線医学総合研究所, 分子イメージング研究センター, センター長 (10360356)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 医用 / 生体画像 / 高磁場MRI / ナノ粒子 / リポソーム / 腫瘍 / 化学療法 / 温度感受性ポリマー

Research Abstract

高磁場MRIを用いて、(1)Ca2+チャネルを通過するマンガン造影剤を使用し、脳虚血後に生じるグリア細胞の増殖であるグリオーシスのin vivo検出および経時的観察に成功した、(2)DDS技術による腫瘍集積性を生かしたフラーレン・マンガン造影剤を使用した微小腫瘍の検出、および超音波/光治療の効果判定と経時的追跡を行った、(3)光イメージングにおいて良好な周波数分解能を持つカンタムドット(Quantum dots; QD)を使用した光・MRIのハイブリッド造影剤の開発に成功した。

Research Products

• [Journal Article] Developments of sulcal pattern and subcortical structures of the forebrain in cynomolgus monkey fetuses: 7-tesla magnetic resonance imaging provides high reproducibility of gross structural changes (2009)
  • Author(s): Sawada K, Sun XZ, Fukunishi K, Kashima M, Sakata-Haga H, Tokado H, Aoki I, Fukui Y
  • Journal Title: Brain Struct Funct. 2009 Feb 12
  • Peer Reviewed
• [Journal Article] Nitroxyl Radicals for Labeling of Conventional Therapeutics and Noninvasive Magnetic Resonance Imaging of Their Permeability for Blood-Brain Barrier: Relationship between Structure, Blood Clearance, and MRI Signal Dynamic in the Brain (2009)
  • Author(s): Zhelev Z, Bakalova R, Aoki I, Matsumoto KI, Gadjeva V, Anzai K, Kanno I.
  • Journal Title: Mol Pharm. 2009 Feb 10
  • Peer Reviewed
• [Journal Article] Visualization of free radical reactions in an aqueous sample irradiated by 290 MeV carbon beam (2009)
  • Author(s): Matsumoto KI, Nagata K, Yamamoto H, Endo K, Anzai K, Aoki I.
  • Journal Title: Magnetic Resonance in Medicine 61(5) Pages: 1033-1039
  • Peer Reviewed
• [Journal Article] Developments of sulcal pattern and subcortical structures of the forebrain in cynomolgus monkey fetuses : 7-tesla magnetic resonance imaging provides high reproducibility of gross structural changes (2009)
  • Author(s): Sawada K, Sun XZ, Fukunishi K, Kashima M, Sakata-Haga H, Tokado H, Aoki I, Fukui Y.
  • Journal Title: Brain Structure and Function
  • Peer Reviewed
• [Journal Article] Nitroxyl Radicals for Labeling of Conventional Therapeutics and Noninvasive Magnetic Resonance Imaging of Their Permeability for Blood-Brain Barrier : Relationship between Structure, Blood Clearance, and MRI Signal Dynamic in the Brain(DOI:10.1021/mp800175k) (2009)
  • Author(s): Zhelev Z, Bakalova R, Aoki I, Matsumoto KI, Gadjeva V, Anzai K, Kanno I.
  • Journal Title: Molecular Pharmaceutics
  • Peer Reviewed
• [Journal Article] Nitroxyl radicals as low toxic spin-labels for non-invasive magnetic resonance imaging of blood-brain barrier permeability for conventional therapeutics (2009)
  • Author(s): Zhelev Z, Bakalova R, Aoki I, Matsumoto K, Gadjeva V, Anzai K, Kanno I.
  • Journal Title: Chemical Communications Issue 1 Pages: 53-55
  • Peer Reviewed
• [Journal Article] Nitroxyl radicals as low toxic spin-labels for non-invasive magnetic resonance imaging of blood-brain barrier permeability for conventional therapeutics (2008)
  • Author(s): Zhelev Z, Bakalova R, Aoki I, Matsumoto K, Gadjeva V, Anzai K, Kanno I
  • Journal Title: Chem Commun (Camb)2009 Jan 7;(1):53-5. Epub 2008 Nov 13
  • Peer Reviewed
• [Journal Article] Multimodal silica-shelled quantum dots: direct intracellular delivery, photosensitization, toxic, and microcirculation effects (2008)
  • Author(s): Bakalova R, Zhelev Z, Aoki I, Masamoto K, Mileva M, Obata T, Higuchi M, Gadjeva V, Kanno I
  • Journal Title: Bioconjug Chem 2008 Jun;19(6 Pages: 1135-1142
  • Peer Reviewed
• [Journal Article] Multimodal silica-shelled quantum dots : direct intracellular delivery, photosensitization, toxic, and microcir culation effects (2008)
  • Author(s): Bakalova R, Zhelev Z, Aoki I, Masamoto K, Mileva M, Obata T, Higuchi M, Gadjeva V, Kanno I.
  • Journal Title: Bioconjugate Chemistry 19(6) Pages: 1135-1142
  • Peer Reviewed
• [Journal Article] Detection of cortical laminar architecture using manganese-enhanced MRI (2008)
  • Author(s): Afonso C.Silva, Jung Hee Lee, Carolyn W-H.Wu, Jason Tucciarone, Galit Pelled, Ichio Aoki, Alan P.Koretsky
  • Journal Title: Journal of Neuroseience Methods 167 Pages: 246-257
  • Peer Reviewed
• [Journal Article] 動物用MRイメージング計測 (2008)
  • Author(s): 青木 伊知男
  • Journal Title: 遺伝子医学MOOK 9 Pages: 101-106
• [Journal Article] DDSによるMR分子イメージングヘ (2008)
  • Author(s): 青木 伊知男、バカロバルミアナ
  • Journal Title: Drug Delivery System 23 Pages: 61-68
  • Peer Reviewed
• [Journal Article] Multimodal and biocompatible quantum dots - strategy of design (2007)
  • Author(s): Bakalova, R., Zhelev, Z., Aoki, I., Kanno, I
  • Journal Title: Nature Photonics 1(9) Pages: 487-489
  • Peer Reviewed
• [Journal Article] Neuronal response to Shepard's tones. An auditory fMRI study using multifractal analysis (2007)
  • Author(s): Shimizu Y, Umeda M, Mano H, Aoki I, Higuchi T, Tanaka C
  • Journal Title: Brain Res Epub 2007 Oct 16 Pages: 113-123
  • Peer Reviewed
• [Journal Article] Neuronal response to Shepard's tones: an auditory fMRI study using multifractal analysis (2007)
  • Author(s): Yu Shimizu, Masahiro Umeda, Ichio Aoki, Toshihiro Higuchi, Chuzo Tanaka, et. al.
  • Journal Title: Brain Research 1186 Pages: 113-123
  • Peer Reviewed
• [Journal Article] Designing quantum-dots probes (2007)
  • Author(s): Rumiana Bakalova-Zheleva, Zhivko Zhelev, Ichio Aoki, Iwao Kanno
  • Journal Title: Nature Photonics 1 Pages: 487-489
  • Peer Reviewed
• [Journal Article] Koretsky AP. Detection of cortical laminar architecture using manganese-enhanced MRI
  • Author(s): Silva AC, Lee JH, Wu CW, Tucciarone J, Pelled G, Aoki I
  • Journal Title: J Neurosci Methods 30;167(2) Pages: 246-257
  • Peer Reviewed
• [Presentation] 高磁場MRIによる分子イメージングへのアプローチ (2008)
  • Author(s): 青木 伊知男
  • Organizer: 第1回創薬とイメージングに関するシンポジウム
  • Place of Presentation: 大阪市
  • Year and Date: 2008-02-22
• [Presentation] Development of Multimodal Thermosensitive Polymer-Modified Liposome (MTPL) as a Carrier for MRI and Optical Imaging (2008)
  • Author(s): Ichio Aoki, Misao Yoneyama, Jun Hirose, Yuzuru Minemoto, Takayoshi Koyama, Sadahito Aoshima, Jeff Kershaw, Kenji Kono, Yukihito Ishizaka, Iwao Kanno
  • Organizer: 2008 World Molecular Imaging Congress 1569
  • Place of Presentation: Nice, France
• [Presentation] In Vivo Optical and Magnetic Resonance Imaging of Electroporation-Mediated Transgene Expression in Experimental Tumors (2008)
  • Author(s): Winn Aung, Sumitaka Hasegawa, Michiko Koshikawa, Takayuki Obata, Hiroo Ikehira, Takako Furukawa, Ichio Aoki, Tsuneo Saga.
  • Organizer: 2008 World Molecular Imaging Congress, 698
  • Place of Presentation: Nice, France
• [Presentation] In-Vivo Application of Manganese-Labeled Immunocytes (2008)
  • Author(s): Kenichi Odaka, Ichio Aoki, Junji Moriya, Kaoru Tateno, Hiroyuki Tadokoro, Tohru Minamino, Toshiaki Irie, Issei Komuro, Kanno Iwao
  • Organizer: 2008 World Molecular Imaging Congress, 1034
  • Place of Presentation: Nice, France
• [Presentation] Exploring Molecular Targets for Mesothelioma Imaging (2008)
  • Author(s): Michiko Koshikawa, Sumitaka Hasegawa, Isao Takahashi, Misao Hachiya, Takako Furukawa, Makoto Akashi, Satoshi Yoshida, Ichio Aoki, Tsuneo Saga
  • Organizer: 2008 World Molecular Imaging Congress, 1141
  • Place of Presentation: Nice, France
• [Presentation] Compartmentalized Diffusion-Weighted Fmri Signal in Alpha-Chloralose Anesthetized Rat Somatosensory Cortex at 7 T (2008)
  • Author(s): Joonas A. Autio, Jeff Kershaw, Takayuki Obata, Sayaka Shibata, Daigo Kuroiwa, Iwao Kanno, Ichio Aoki
  • Organizer: 2008 World Molecular Imaging Congress, 1918
  • Place of Presentation: Nice, France
• [Presentation] Quantum Dots in Multimodal Imaging: Probe Design, Spectral Characteristics, and Application (2008)
  • Author(s): Zhivko Zhelev, Bakalova Rumiana, Aoki Ichio, Gadjeva Veselina, Kanno Iwao
  • Organizer: 2008 World Molecular Imaging Congress, 1595
  • Place of Presentation: 2008 World Molecular Imaging Congress, 1595
• [Presentation] Multimodal Molecular Probes: Chemical Design, Spectral Characteristics and Application for In Vitro and In Vivo Imaging (2008)
  • Author(s): Rumiana Bakalova, Zhivko Zhelev, 青木伊知男, 松本謙一郎, Veselina Gadjeva, 安西和紀, 菅野 巖
  • Organizer: 第3回日本分子イメージング学会
  • Place of Presentation: 埼玉
• [Presentation] 温度感受性リポソームによるMRI/蛍光の複合機能プローブの開発-腫瘍検出、薬剤放出の可視化、化学療法のために (2008)
  • Author(s): 青木伊知男、米山 操、廣瀬 淳、峯本 譲、小山貴芳、青島貞人、Jeff Kershaw、河野健司、石坂幸人、菅野 巖
  • Organizer: 第3回日本分子イメージング学会
  • Place of Presentation: 埼玉
• [Presentation] マウス実験腫瘍へのエレクトロポレーションによる遺伝子導入とその遺伝子発現のin vivo MRI/蛍光イメージング (2008)
  • Author(s): 長谷川純崇、Winn Aung、米山操、越川道子、楢崎美智子、小畠隆行、古川高子、青木伊知男、佐賀恒夫
  • Organizer: 第3回日本分子イメージング学会
  • Place of Presentation: 埼玉
• [Presentation] 血管新生モニタリングのための磁気共鳴イメージング造影剤の作成 (2008)
  • Author(s): 城潤一郎、林 雪、米山操、柴田さやか、青木伊知男、田畑泰彦
  • Organizer: 第3回日本分子イメージング学会
  • Place of Presentation: 埼玉
• [Presentation] Thermosensitive Polymer-modified Liposome as a Multimodal and Multifunctional Carrier for MRI and Optical Imaging : Tumor Detection, Visualization of Triggered Drug Release, and Chemotherapy (2008)
  • Author(s): Ichio Aoki, Misao Yoneyama, Jeffrey Kershaw, Iwao Kanno, et. al
  • Organizer: ISMRM 16th Scientific Meeting and Exhibition
  • Place of Presentation: Tront, Canada
• [Presentation] A social eating party induced affiliation behavior of chick reared in socially deprived condition (2008)
  • Author(s): Mamiko Koshiba, Takashi Ogino, Ichio Aoki, et. al.
  • Organizer: CINP Pacific-Asia Regional Meeting
  • Place of Presentation: Kuala Lumpur,Malaysia
• [Presentation] マンガン増感MRI(MEMRI)によるラット前肢末梢神経経路トレーシング (2007)
  • Author(s): 青木伊知男、Afonso Silva、Alan Koretsky
  • Organizer: 第35回日本磁気共鳴医学会
  • Place of Presentation: 神戸
• [Presentation] マンガン増感MRIによる移植細胞標識の試み (2007)
  • Author(s): 小高謙一、青木伊知男、米山 操、森谷純治、舘野 馨、田所 裕之、南野 徹、小室一成、入江俊章、鈴木和年、菅野 巖
  • Organizer: 第35回日本磁気共鳴医学会
  • Place of Presentation: 神戸
• [Presentation] 社会性コミュニケーション行動に関与する脳領域の7T MRIによる解析 (2007)
  • Author(s): 小柴満美子、荻野孝史、青木伊知男、池平博夫、菅野 巖、中村 俊
  • Organizer: 第35回日本磁気共鳴医学会大会
  • Place of Presentation: 神戸
• [Presentation] Polymer coating of quantum dots is crucial for their in vivo optical imaging application (2007)
  • Author(s): Bakalova R, Masamoto K, Zhelev Z, Aoki I, Obata T, Kanno I
  • Organizer: Joint Molecular Imaging Conference 0366
  • Place of Presentation: Providence, USA
• [Presentation] 複合イメージングと生物学診断のためのカンタムドットを利用した分子プローブについて (2007)
  • Author(s): Bakalova Rumiana、Zhivko Zhelev、青木伊知男、Genoveva Zlateva、小畠隆行、菅野 巖
  • Organizer: 第2回日本分子イメージング学会学術集会
  • Place of Presentation: 福井
• [Presentation] 高速・定量値マッピングのマンガン増感MRIへの適用 (2007)
  • Author(s): 米山 操、Jeff Kershaw、菅野 巖、青木伊知男
  • Organizer: 第2回日本分子イメージング学会学術集会
  • Place of Presentation: 福井
• [Presentation] マンガン増感MRIによる移植免疫細胞の標識技術の開発 (2007)
  • Author(s): 小高謙一、青木伊知男、米山 操、森谷純治、舘野 馨、田所 裕之、南野 徹、小室一成、入江俊章、鈴木和年、菅野 巖
  • Organizer: 第2回日本分子イメージング学会学術集会
  • Place of Presentation: 福井
• [Presentation] Detection of Reactive Gliosis using Manganese-enhanced MRI (MEMRI). International Society for Magnetic Resonance in Medicine (2007)
  • Author(s): Y. Kawai, I. Aoki, N. Matsumoto, M. Umeda, T. Higuchi, J. Kershaw, A. C. Silva, C. Tanaka
  • Organizer: Scientific Meeting and Exhibition
  • Place of Presentation: Berlin, Germany
• [Presentation] Thermosensitive Polymer-Modified Liposome as a Multimodal and Multifunctional Carrier for MRI and Optical Imaging: Tumor Detection, Visualization of Triggered Drug Release, and Chemotherapy (2007)
  • Author(s): Aoki I, Yoneyama M, Hirose J, Minemoto Y, Koyama T, Aoshima S, Kershaw J, Kono K, Ishizaka Y, Kanno I.
  • Organizer: International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition
• [Presentation] マンガン増感MRIによる移植細胞標識の試み (2007)
  • Author(s): 小高 謙一、青木 伊知男, ら
  • Organizer: 第35回日本磁気共鳴医学会大会
  • Place of Presentation: 神戸市
• [Presentation] Quantum Dot-Based Nanobioprobes for Multimodal Imaging and Biomedical Diagnostics (2007)
  • Author(s): Rumiana Bakalova-Zheleva, Zhivko Zhelev, Ichio Aoki, et. al.
  • Organizer: EuroNanoForum2007
  • Place of Presentation: Dusseldorf,Germany
• [Presentation] Quantum dot-based nanobioprobes for multimodal imaging and biomedical diagnostics (2007)
  • Author(s): Rumiana Bakalova-Zheleva, Zhivko Zhelev, Ichio Aoki, et. al.
  • Organizer: 2nd International Symposium Advanced micro-and mesoporous materials
  • Place of Presentation: Varna,Bulgaria
• [Presentation] Quantum dot-based molecular probes for multimodal imaging and biomedical diagnostics (2007)
  • Author(s): Rumiana Bakalova-Zheleva, Zhivko Zhelev, Ichio Aoki
  • Organizer: 第2回日本分子イメージング学会総会・学術集会
  • Place of Presentation: 福井市
• [Presentation] Polymer coating of quantum dots is crucial for their in vivo optical imaging application (2007)
  • Author(s): Rumiana Bakalova-Zheleva, Kazuto Masamoto, Zhivko Zhelev, Ichio Aoki, et. al.
  • Organizer: Joint Molecular Imaging Conference2007
  • Place of Presentation: Providence,USA
• [Presentation] 高磁場磁気共鳴画像法による細胞・分子イメージング〜マンガン増感MRI(MEMRI)を中心に〜 (2007)
  • Author(s): 青木 伊知男
  • Organizer: 第28回日本炎症・再生医学会
  • Place of Presentation: 東京
• [Presentation] マンガン増感MRI(MEMRI)によるラット前肢末梢神経経路トレーニング (2007)
  • Author(s): 青木 伊知男, ら
  • Organizer: 第35回日本磁気共鳴医学会大会
  • Place of Presentation: 神戸市
• [Presentation] 高速・定量値マッピングのマンガン増感MRIへの適用 (2007)
  • Author(s): 米山 操、Kershaw Jeffrey、菅野 巖、青木 伊知男
  • Organizer: 第2回日本分子イメージング学会総会・学術集会
  • Place of Presentation: 福井市
• [Book] Bakalova Rumian.DDSによる「MR分子イメージング」へ(in press) (2008)
  • Author(s): 青木伊知男
  • Publisher: Drug Delivery System
• [Book] 動物用MRイメージング計測、ますます広がる分子イメージング技術 : 生物医学研究から先端医療、創薬研究までを支える分子イメージング技術(in press) (2008)
  • Author(s): 青木伊知男
  • Publisher: 遺伝子医学MOOK ; 9
• [Book] Rumiana Bakalova、DDS による「MR分子イメージング」へ、Drug Delivery System、分子イメージングとDDS、総説、23(1) (2008)
  • Author(s): 青木伊知男
• [Book] .MRIによる分子イメージングの研究動向50(12) (2007)
  • Author(s): 青木伊知男
  • Publisher: 放射線科学
• [Book] 動物用MRイメージング計測、遺伝子医学MOOK9号「生物医学研究から先端医療、創薬研究までを支える分子イメージング技術」、第1章、2.MRIによる分子イメージングISBN978-4-944157-39-6
  • Author(s): 青木伊知男
• [Remarks]
  • URL: http://www.nirs.go.jp/research/division/mic/group/g_sentan-seitai-th.html
• [Patent(Industrial Property Rights)] 常磁性金属含有ポリアミドアミンデンドロン脂質 (2008)
  • Filing Date: 2008-04-25