Construction of antibody-based molecular imaging techniques to analyze a development of tumor angiogenesis.

2010 Fiscal Year Final Research Report

• Project/Area Number: 20200017
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: Biomedical engineering/Biological material science; Medical pharmacy
• Research Institution: Osaka University
• Principal Investigator: MUKAI Yohei Osaka University, 大学院・薬学研究科, 助教 (60444501)
• Co-Investigator(Kenkyū-buntansha): SEINO Satoshi 大阪大学, 大学院・工学研究科, 講師 (90432517) ; OKADA Yoshiaki 大阪大学, 大学院・薬学研究科, 助教 (50444500) ; MORITA Masahito 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (30381594) ; HATAZAWA Jun 大阪大学, 大学院・医学研究科, 教授 (70198745)
• Co-Investigator(Renkei-kenkyūsha): NAKAGAWA Shinsaku 大阪大学, 大学院・薬学研究科, 教授 (70207728) ; YAMAMOTO Takao 大阪大学, 大学院・工学研究科, 教授 (00174798) ; DOI Takefumi 大阪大学, 大学院・薬学研究科, 教授 (00211409) ; INUBUSHI Toshiro 滋賀医科大学, MR医学総合研究センター, 教授 (20213142) ; KANAI Yasukazu 大阪大学, 大学院・医学研究科, 助教 (80467555)
• Project Period (FY): 2008 – 2010
• Keywords: 医用・生体画像 / 腫瘍血管 / 抗体 / SPECT / MRI

Research Abstract

We aim to develop a method to analyze a progress of tumor blood vessels by antibody-based imaging using anti-tumor endothelial marker antibodies. In the assessment of these antibodies, we show that cell-internalizing antibody can accumulate into the endothelial cells efficiently. This property may be useful for specific labeling of tumor endothelial cells. In the development of a novel MR imaging agent, we show that PEG-modified gold-iron oxide nanoparticles can accumulate in the tumor, and they can visualize a tumor tissue using MRI. In addition, we also developed a method to modify antibodies on a tip of PEG. It may be novel tumor endothelial specific MR imaging agent. We also developed a method of antibody labeling using 123I. We are challenging an antibody based SPECT imaging with help of Dr. Hatazawa, Osaka University. In the future, these antibody-based technologies will be useful for the analysis of the progress of tumor blood vessels.

Research Products

• [Journal Article] Vascular bed-specific regulation of the von Willebrand factor promoter in the heart and skeletalmuscle (2010)
  • Author(s): Liu J, Yuan L, Molema I, Regan E, Janes L, Beeler D, Spokes K, Okada Y, Minami T, Oettgen P, Aird WC
  • Journal Title: Blood (in press)
  • Peer Reviewed
• [Journal Article] Cellular and molecular MR and fluorescence imaging. (2010)
  • Author(s): 森田将史
  • Journal Title: 日本放射線技術学会雑誌 (in press )
  • Peer Reviewed
• [Journal Article] Solution of the Structure of the TNF-TNFR2 Complex. (2010)
  • Author(s): Mukai Y, Nakamura T, Yoshikawa M, Yoshioka Y, Tsunoda S, Nakagawa S,, Yamagata Y, Tsutsumi Y
  • Journal Title: Sci Signal. 3(148) Pages: 83
  • Peer Reviewed
• [Journal Article] Simple PEG Conjugation of SPIO via an Au-S Bond Improves Its Tumor Targeting Potency as a Novel MR Tumor Imaging Agent. (2010)
  • Author(s): Kojima H, Mukai Y, Yoshikawa M, Kamei K, Yoshikawa T, Morita M, Inubushi T, Yamamoto TA, Yoshioka Y, Okada N, Seino S, Nakagawa S,
  • Journal Title: Bioconjug Chem. 21(6) Pages: 1026-1031
  • Peer Reviewed
• [Journal Article] 腫瘍MRイメージングにおける造影剤開発 (2010)
  • Author(s): 向洋平、中川晋作
  • Journal Title: JSMI Report. 3(1) Pages: 14-17
  • Peer Reviewed
• [Journal Article] Direct cell-entry of gold/iron-oxide magnetic nanoparticles in adenovirus mediated gene delivery. (2009)
  • Author(s): Kamei K, Mukai Y, Kojima H, Yoshikawa T, Yoshikawa M, Kiyohara G, Yamamoto TA, Yoshioka Y, Okada N, Seino S, Nakagawa S,
  • Journal Title: Biomaterials. 30(9) Pages: 1809-1814
  • Peer Reviewed
• [Journal Article] Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1. (2009)
  • Author(s): Baek KH, Zaslavsky A, Lynch RC, Britt C, Okada Y, Siarey RJ, Lensch MW, Park IH, Yoon SS, Minami T, Korenberg JR, Folkman J, Daley GQ, Aird WC, Galdzicki Z, Ryeom S
  • Journal Title: Nature. 459(7250) Pages: 1126-1130
  • Peer Reviewed
• [Journal Article] Dispersibility improvement of gold/iron-oxide composite nanoparticles by polyethylenimine modification. (2009)
  • Author(s): Seino S, Matsuoka Y, Kinoshita T, Nakagawa S,, Yamamoto TA
  • Journal Title: J Magn Magn Mater. 321(10) Pages: 1404-1407
  • Peer Reviewed
• [Journal Article] A GABP-binding element in the Robo4 promoter is necessary for endothelial expression in vivo. (2008)
  • Author(s): Okada Y, Jin E, Nikolova-Krstevski V, Yano K, Liu J, Beeler D, Spokes K, Kitayama M, Funahashi N, Doi T, Janes L, Minami T, Oettgen P, Aird WC.
  • Journal Title: Blood. 112(6) Pages: 2336-2339
  • Peer Reviewed
• [Journal Article] MRI-based correction for partial-volume effect improves detectability of intractable epileptogenic foci on 123I-iomazenil brain SPECT images. (2008)
  • Author(s): Kato H, Shimosegawa E, Oku N, Kitagawa K, Kishima H, Saitoh Y, Kato A, Yoshimine T, Hatazawa J
  • Journal Title: J Nucl Med. 49 Pages: 383-389
  • Peer Reviewed
• [Presentation] Ligand independent assembly of purified soluble Magic Roundabout (Robo4), a tumor-specific endothelial marker (2009)
  • Author(s): Yoshikawa M, Mukai Y, Okada Y, Yoshioka Y, Tsunoda S, Tsutsumi Y, Okada N, Aird WC, Doi T, Nakagawa S
  • Organizer: ECCO 15 and 34th ESMO Multidisciplinary Congress
  • Place of Presentation: Berlin (Germany)
  • Year and Date: 20090920-20090924
• [Presentation] Design of tumor targeting magnetic resonance imaging (MRI) agent based on gold/iron-oxide composite nanoparticle. (2009)
  • Author(s): Kojima H, Mukai Y, Kamei K, Seino S, Morita M, Inubushi T, Yoshioka Y, Okada N, Nakagawa S
  • Organizer: ECCO 15 and 34th ESMO Multidisciplinary Congress
  • Place of Presentation: Berlin (Germany)
  • Year and Date: 20090920-20090924
• [Presentation] Direct cell entry of gold/iron-oxide magnetic nanoparticles in adenovirus mediated gene delivery (2009)
  • Author(s): Mukai Y, Kojima H, Yoshikawa T, Kamei K, Yoshikawa M, Yamamoto TA, Yoshioka Y, Okada N, Seino S, Nakagawa S
  • Organizer: ECCO 15 and 34th ESMO Multidisciplinary Congress
  • Place of Presentation: Berlin (Germany)
  • Year and Date: 20090920-20090924
• [Presentation] 生体内応用を目指したPEG化金/酸化鉄磁性複合ナノ粒子の合成 (2009)
  • Author(s): 清野智史、山中誠之、中川貴、小島拓記、向洋平、中川晋作、山本孝夫
  • Organizer: 第33回日本磁気学会学術講演会
  • Place of Presentation: 長崎
  • Year and Date: 20090912-20090915
• [Presentation] 金磁性複合ナノ粒子のバイオ・DDS分野への展開 (2009)
  • Author(s): 向洋平
  • Organizer: 第3回「ナノメディスン・アプリケーション研究会」
  • Place of Presentation: 大阪
  • Year and Date: 2009-09-16
• [Presentation] 金磁性複合ナノ粒子のバイオ分野への応用 (2009)
  • Author(s): 向洋平
  • Organizer: 第31回ナノバイオ磁気工学専門研究会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-23
• [Presentation] Robo4プロモーターに存在するGABP結合配列のin vivoにおける重要性 (2009)
  • Author(s): 岡田欣晃、金恩京、北山美絵、舟橋伸昭、矢野喜一郎、Aird WC、土井健史
  • Organizer: 第10回Pharmaco-Hematologyシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2009-06-20
• [Presentation] 超高分解能半導体PETを用いた124I-iomazenilによるラット脳中枢性ベンゾジアゼピン受容体分布の画像化およびin vivoにおける基礎的検討 (2008)
  • Author(s): 金井泰和,船木善仁,山崎浩道,菊池洋平,松山成男,高沢正志、今泉昌男、中村賢治,中沢浩一,下瀬川恵久,石井慶造,畑澤順
  • Organizer: 第86回放射性医薬品・画像診断薬研究会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-06
• [Presentation] Synthesis of^124I-iomazenil and imaging of central benzodiazepine receptor distribution in rat brain by means of semiconductor high resolution animal PET scanner. (2008)
  • Author(s): Kanai Y, Yamazaki H, Funaki Y, Matsuyama S, Kikuchi Y, Sakamaki M, Shimosegawa E, Ishii K, Hatazawa J
  • Organizer: 第55回米国核医学会議
  • Place of Presentation: ニューオリンズ
  • Year and Date: 2008-06-14
• [Presentation]
  • Author(s): 岡田欣晃、金恩京、北山美絵、舟橋伸昭
• [Remarks] ホームページ等
• [Remarks] 大阪大学研究者総覧(向洋平)
  • URL: http://www.dma.jim.osaka-u.ac.jp/kg-portal/aspI/RX0011D.asp?UNO=15207&page=1
• [Patent(Industrial Property Rights)] MRI造影剤 (2010)
  • Inventor(s): 向洋平、清野智史、森田将史、中川貴、中川晋作
  • Industrial Property Rights Holder: 大阪大学
  • Industrial Property Number: 特願2010-041460
  • Filing Date: 20100200