Phosphorescent Light-emitting lridium Complexes Serve as a Hypoxia-sensing Probe for Tumor Imaging in Living Animals.

• Project/Area Number: 21200077
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: Physical pharmacy; Applied pharmacology
• Research Institution: Akita Prefectural University (2011); Gunma University (2009-2010)
• Principal Investigator: HOSAKA Masahiro 秋田県立大学, 生物資源科学部, 教授 (80311603)
• Co-Investigator(Kenkyū-buntansha): YOSHIHARA Toshitada 群馬大学, 大学院・工学研究科, 助教 (10375561)
• Co-Investigator(Renkei-kenkyūsha): IIDA Yasuhiko 鈴鹿医療科学大学, 薬学部, 教授 (60252425)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥27,690,000 (Direct Cost: ¥21,300,000、Indirect Cost: ¥6,390,000); Fiscal Year 2011: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2010: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000); Fiscal Year 2009: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
• Keywords: イメージング / イリジウム錯体 / 低酸素病態 / 腫瘍 / 可視化

Research Abstract

Iridium complex is a promising organic light-emitting diode material for next generation video displays that emits phosphorescence quenched by oxygen. We focused this oxygen-quenching feature for imaging tumor hypoxia. We used Red light-emitting Ir(btp)_2(acac) (BTP)to image nude mouse-transplanted tumors, and succeed to image tumors. Since BTP is easily modifiable, we synthesized BTP analogues with a longer excitation/emission wavelength. One of them, BTPHSA, depicted clear imaging from tumors transplanted 6-7 mm deep from the skin surface. Another analogue, BTPDM, shines brighter than BTP in tumors, since BTPDM has character to access easily and reach in cells. We suggest that iridium complex materials have a vast potential for imaging hypoxic lesions such as tumor tissues.

Research Products

• [Journal Article] Iridium Complex Probes for Monitoring of Cellular Oxygen Levels and Imaging of Hypoxic Tissues. (2012)
  • Author(s): Yoshihara, T., Kobayashi, A., Oda, M., Hosaka, M., Takeuchi, T., Tobita, S.
  • Journal Title: Proc. SPIE Volume: 8233
• [Journal Article] Ratiometric Molecular Sensor for Monitoring Oxygen Levels in Living Cells. (2012)
  • Author(s): Yoshihara, T., Yamaguchi, Y. , Hosaka, M., Takeuchi, T., Tobita, S.
  • Journal Title: Angew Chem Int Ed Engl. Volume: 51 Pages: 4148-4151
• [Journal Article] Iridium Complex Probes for Monitoring of Cellular Oxygen Levels and Imaging of Hypoxic Tissues (2012)
  • Author(s): Yoshihara, T., Kobayashi, A., Oda, M., Hosaka, M., Takeuchi, T., Tobita, S.
  • Journal Title: Proc.SPIE Volume: 8233 Pages: 82330A-82330A
  • DOI: 10.1117/12.910170
  • Peer Reviewed
• [Journal Article] Ratiometric Molecular Sensor for Monitoring Oxygen Levels in Living Cells (2012)
  • Author(s): Yoshihara, T., Yamaguchi, Y., Hosaka, M., Takeuchi, T., Tobita, S.
  • Journal Title: Angew Chem Int Ed Engl Volume: 51 Issue: 17 Pages: 4148-4151
  • DOI: 10.1002/anie.201107557
  • Peer Reviewed
• [Journal Article] Silylation Enhancement of Photodynamic Activity of Tetraphenylporphyrin Derivative. (2011)
  • Author(s): Horiuchi, H., Kameya, T., Hosaka, M., Yoshimura, K., Kyushin, S., Matsumoto, H., Okutsu, T., Takeuchi, T., Hiratsuka, H.
  • Journal Title: J. Photochem. Photobiol. Volume: 221 Pages: 98-104
• [Journal Article] Development of Iridium(III) Complexes with High Cellular Uptake Efficiency. (2011)
  • Author(s): Yoshihara, T., Ichikawa, K., Hosaka, M., Takeuchi, T., Tobita, S.
  • Journal Title: Photomedicine and Photobiology Volume: 33 Pages: 15-16
• [Journal Article] Luminal Interaction of Phogrin with Carboxypeptidase E for Effective Targeting to Secretory Granules. (2011)
  • Author(s): Saito, N., Takeuchi, T., Kawano, A., Hosaka, M., Hou, N., Torii, S.
  • Journal Title: Traffic Volume: 12 Pages: 499-506
• [Journal Article] Development of Iridium(III) Complexes with High Cellular Uptake Efficiency (2011)
  • Author(s): Yoshihara, T., Ichikawa, K., Hosaka, M., Takeuchi, T., Tobita, S.
  • Journal Title: Photomedicine and Photobiology Volume: 33 Pages: 15-16
  • Peer Reviewed
• [Journal Article] Cholesterol Biosynthesis Pathway Intermediates and Inhibitors Regulate Glucose-stimulated Insulin Secretion and Secretory Granule Formation in Pancreatic beta-Cells. (2010)
  • Author(s): Tsuchiya, M., Hosaka, M., Moriguchi, T., Zhang, S., Suda, M., Yokota-Hashimoto, H., Shinozuka, K., Takeuchi, T. (The first two authors contributed equally to this work.)
  • Journal Title: Endocrinology Volume: 151 Pages: 4705-4716
• [Journal Article] Phosphorescent Light-emitting Iridium Complexes Serve as a Hypoxia-sensing Probe for Tumor Imaging in Living Animals. (2010)
  • Author(s): Zhang, S., Hosaka, M., Yoshihara, T., Negishi, K., Iida, Y., Tobita, S., Takeuchi, T. (The first three authors contributed equally to this work.)
  • Journal Title: Cancer Research Volume: 70 Pages: 4490-4498
• [Journal Article] Secretogranin III: a bridge between core hormone aggregates and the secretory granule membrane. (2010)
  • Author(s): Hosaka, M., Watanabe, T.
  • Journal Title: Endocrine J. Volume: 57 Pages: 275-286
  • NAID: 10029584142
• [Journal Article] Secretogranin III : a bridge between core hormone aggregates and the secretory granule membrane. (2010)
  • Author(s): Hosaka M, Watanabe T
  • Journal Title: Endocrine J Volume: 57 Pages: 275-286
  • NAID: 10029584142
  • Peer Reviewed
• [Journal Article] Cholesterol Analogs Labeled with Novel Silylated Fluorescent Compounds. (2009)
  • Author(s): Moriguchi, T., Hosaka, M., Yosinari, A., Ozaki, A., Takeuchi, T., Shinozuka, K.
  • Journal Title: Chemistry Letters Volume: 38 Pages: 966-967
  • NAID: 10025547099
• [Journal Article] Secretogranin II Binds to Secretogranin III and Forms Secretory Granules with Orexin, Neuropeptide Y and Proopiomelanocortin. (2009)
  • Author(s): Hotta, K., Hosaka, M., Tanabe, A., Takeuchi, T. (The first two authors contributed equally to this work.)
  • Journal Title: J. Endocrinol. Volume: 202 Pages: 13-14
• [Journal Article] Development of photodetection method of tumor using phosphorescence of iridium(III) complexes. (2009)
  • Author(s): Yoshihara, T., Karasawa, Y., Negishi, K., Fushiya, M., Hosaka, M., Takeuchi, T., Tobita, S.
  • Journal Title: Photomedicine and Photobiology Volume: 31 Pages: 13-14
• [Journal Article] Development of photodetection method of tumor using phosphorescence of iridium(III)complexes (2009)
  • Author(s): Yoshihara T, Karasawa Y, Negishi K, Fushiya M, Hosaka M, Takeuchi T, Tobita S
  • Journal Title: Photomedicine and Photobiology 31 Pages: 13-14
• [Journal Article] Cyclophilin C-associated protein regulation of phagocytic functions via NFAT activation in macrophages.
  • Author(s): Yamaguchi, R., Hosaka, M., Torii, S., Hou, N., Saito, N., Yoshimoto, Y., Imai., H., Takeuchi, T.
  • Journal Title: Brain Res. Volume: 1397 Pages: 55-65
• [Journal Article] Luminal Interaction of Phogrin with Carboxypeptidase E for Effective Targeting to Secretory Granules.
  • Author(s): Saito, N., Takeuchi, T., Kawano, A., Hosaka, M., Hou, N., Torii, S.
  • Journal Title: Traffic Volume: (In press)
  • Peer Reviewed
• [Journal Article] Phosphorescent Light-emitting Iridium Complexes Serve as a Hypoxia-sensing Probe for Tumor Imaging in Living Animals
  • Author(s): Zhang S, Hosaka M, Yoshihara T, Negishi K, Iida Y, Tobita S, Takeuchi, T
  • Journal Title: Cancer Research (in press)
  • Peer Reviewed
• [Presentation] 様々な分泌刺激に対する細胞内膜系小器官の応答の解析:下垂体前葉性腺刺激ホルモン産生細胞をモデルとして： (2012)
  • Author(s): 暮地本宙己, 甲賀大輔, 穂坂正博, 牛木辰男, 渡部剛
  • Organizer: 第１１７回日本解剖学会総会
  • Year and Date: 2012-03-26
• [Presentation] Iridiumcomplex probes for monitoring of cellular oxygen levels and imaging of hypoxic tissues (2012)
  • Author(s): Tobita, S., Yoshihara, T., Kobayashi, A., Ichikawa, K., Hosaka, M., Takeuchi, T
  • Organizer: SPIE
• [Presentation] Iridiumcomplex probes for monitoring of cellular oxygen levels and imaging of hypoxictissues (2012)
  • Author(s): Tobita, S., Yoshihara, T., Kobayashi, A., Ichikawa, K., Hosaka, M., Takeuchi, T
  • Organizer: SPIE
  • Place of Presentation: San Francisco, USA
• [Presentation] 生体内低酸素領域を識別するためのイリジウム錯体の開発および生体内発光特性 (2011)
  • Author(s): 吉原利忠, 市川和貴, 大堀優佳, 小林敦, 穂坂正博, 竹内利行, 飛田成史
  • Organizer: 第５回分子科学討論会
  • Year and Date: 2011-09-23
• [Presentation] イリジウム錯体のりん光寿命測定によるin vivo酸素濃度計測 (2011)
  • Author(s): 小林敦, 吉原利忠, 穂坂正博, 竹内利行, 飛田成史
  • Organizer: 第５回分子科学討論会
  • Year and Date: 2011-09-23
• [Presentation] 近赤外りん光を示すイリジウム錯体を用いた低酸素がん腫瘍イメージング (2011)
  • Author(s): 大堀優佳, 吉原利忠, 小林敦, 穂坂正博, 竹内利行, 飛田成史
  • Organizer: 第５回分子科学討論会
  • Year and Date: 2011-09-23
• [Presentation] イリジウム錯体のりん光を用いた低酸素がん腫瘍イメージング:配位子の構造が細胞内動態に及ぼす影響 (2011)
  • Author(s): 市川和貴, 吉原利忠, 小林敦, 穂坂正博, 竹内利行, 飛田成史
  • Organizer: 第５回分子科学討論会
  • Year and Date: 2011-09-23
• [Presentation] 生体内低酸素領域を識別するためのイリジウム錯体の開発および生体内発光特性 (2011)
  • Author(s): 吉原利忠, 市川和貴, 大堀優佳, 小林敦, 穂坂正博, 竹内利行, 飛田成史
  • Organizer: 第5回分子科学討論会
  • Place of Presentation: 札幌市
  • Year and Date: 2011-09-23
• [Presentation] イリジウム錯体のりん光寿命測定によるin vivo酸素濃度計測 (2011)
  • Author(s): 小林敦, 吉原利忠, 穂坂正博, 竹内利行, 飛田成史
  • Organizer: 第5回分子科学討論会
  • Place of Presentation: 札幌市
  • Year and Date: 2011-09-23
• [Presentation] 近赤外りん光を示すイリジウム錯体を用いた低酸素がん腫瘍イメージング (2011)
  • Author(s): 大堀優佳, 吉原利忠, 小林敦, 穂坂正博, 竹内利行, 飛田成史
  • Organizer: 第5回分子科学討論会
  • Place of Presentation: 札幌市
  • Year and Date: 2011-09-23
• [Presentation] イリジウム錯体のりん光を用いた低酸素がん腫瘍イメージング:配位子の構造が細胞内動態に及ぼす影響 (2011)
  • Author(s): 市川和貴, 吉原利忠, 小林敦, 穂坂正博, 竹内利行, 飛田成史
  • Organizer: 第5回分子科学討論会
  • Place of Presentation: 札幌市
  • Year and Date: 2011-09-23
• [Presentation] アミノクマリン誘導体を蛍光団とする蛍光性コレステロールの開発と光物理特性 (2011)
  • Author(s): 追川竜介, 吉原利忠, 村瀬秋子, 穂坂正博, 飛田成史
  • Organizer: 2011年光化学討論会
  • Year and Date: 2011-09-07
• [Presentation] 高い酸素応答性を有する近赤外発光イリジウム錯体の開発と光物理特性 (2011)
  • Author(s): 八木橋美樹, 吉原利忠, 穂坂正博, 竹内利行, 飛田成史
  • Organizer: 2011年光化学討論会
  • Year and Date: 2011-09-07
• [Presentation] アミノクマリン誘導体を蛍光団とする蛍光性コレステロールの開発と光物理特性 (2011)
  • Author(s): 追川竜介、吉原利忠、村瀬秋子、穂坂正博、飛田成史
  • Organizer: 2011年光化学討論会
  • Place of Presentation: 宮崎市
  • Year and Date: 2011-09-07
• [Presentation] 高い酸素応答性を有する近赤外発光イリジウム錯体の開発と光物理特性 (2011)
  • Author(s): 八木橋美樹、吉原利忠、穂坂正博, 竹内利行、飛田成史
  • Organizer: 2011年光化学討論会
  • Place of Presentation: 宮崎市
  • Year and Date: 2011-09-07
• [Presentation] 高い細胞膜透過性を示すイリジウム錯体の開発およびin vivo光イメージング (2011)
  • Author(s): 吉原利忠、市川和貴、穂坂正博、竹内利行、飛田成史
  • Organizer: 第33回日本光医学・光生物学会
  • Place of Presentation: 大阪市
  • Year and Date: 2011-07-23
• [Presentation] がんの光イメージングのためのりん光プローブ分子の開発 (2011)
  • Author(s): 吉原利忠, 市川和貴, 八木橋美樹, 穂坂正博, 竹内利行, 飛田成史
  • Organizer: 第６回日本分子イメージング学会学術大会
  • Year and Date: 2011-05-22
• [Presentation] がんの光イメージングのためのりん光プローブ分子の開発 (2011)
  • Author(s): 吉原利忠、市川和貴、八木橋美樹、穂坂正博、竹内利行、飛田成史
  • Organizer: 第6回日本分子イメージング学会学術大会
  • Place of Presentation: 神戸市
  • Year and Date: 2011-05-22
• [Presentation] Developments of Hypoxia-Sensing Probes with High Cellular Uptake Efficiency (2011)
  • Author(s): Yoshihara, T., Ichikawa, K., Hosaka, M., Takeuchi, T., Tobita, S.
  • Organizer: The First International Symposium on Element Innovation
• [Presentation] Iridium complex, a phosphorescent light-emitting diode material, serves as a novel chemical probe for imaging hypoxic tumor tissues. (2010)
  • Author(s): Masahiro Hosaka
  • Organizer: 2010 World Molecular Imaging Congress
  • Year and Date: 2010-09-11
• [Presentation] Iridium complex, a phosphorescent light-emitting diode material, serves as a novel chemical probe for imaging hypoxic tumor tissues (2010)
  • Author(s): Masahiro Hosaka
  • Organizer: 2010 World Molecular Imaging Congress
  • Place of Presentation: 京都
  • Year and Date: 2010-09-11
• [Presentation] Sorting mechanism of regulated secretory proteins by Secretogranin III (2009)
  • Author(s): Masahiro Hosaka
  • Organizer: 15th International Symposia on Chromaffin Cell Biology
  • Year and Date: 2009-11-16
• [Presentation] Sorting mechanism of regulated secretory proteins by Secretogranin III (2009)
  • Author(s): 穂坂正博
  • Organizer: 15th International Symposia on Chromaffin Cell Biology
  • Place of Presentation: Merida, MEXICO
  • Year and Date: 2009-11-16
• [Presentation] 低酸素環境感知プローブイリジウム錯体による腫瘍イメージング (2009)
  • Author(s): 穂坂正博, 吉原利忠, 張少娟, 飯田靖彦, 遠藤啓吾, 飛田成史, 竹内利行
  • Organizer: 日本生化学会
  • Year and Date: 2009-10-24
• [Presentation] 低酸素環境感知プローブイリジウム錯体による腫瘍イメージング (2009)
  • Author(s): 穂坂正博、吉原利忠、張少娟、飯田靖彦、遠藤啓吾、飛田成史、竹内利行
  • Organizer: 日本生化学会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2009-10-24
• [Presentation] イリジウム錯体の燐光を利用した癌の光検出法の開発 (2009)
  • Author(s): 吉原利忠, 唐澤靖幸, 根岸一也, 伏屋昌則, 穂坂正博, 竹内利行, 飛田成史
  • Organizer: 日本光医学会・光生物学会
  • Year and Date: 2009-07-24
• [Presentation] イリジウム錯休の燐光を利用した癌の光検出法の開発 (2009)
  • Author(s): 吉原利忠, 唐澤靖幸, 根岸一也, 伏屋昌則, 穂坂正博, 竹内利行, 飛田成史
  • Organizer: 日本光医学会・光生物学会
  • Place of Presentation: 梅田スカイビル
  • Year and Date: 2009-07-24
• [Presentation] 癌のin vivoりん光イメージングを指向したイリジウム錯体の改良 (2009)
  • Author(s): 吉原利忠, 根岸一也, 伏屋昌則, 穂坂正博, 竹内利行, 飛田成史
  • Organizer: 日本分子イメージング学会
  • Year and Date: 2009-05-15
• [Presentation] 癌の in vivo りん光イメージングを指向したイリジウム錯体の改良 (2009)
  • Author(s): 吉原利忠、根岸一也、伏屋昌則、穂坂正博、竹内利行、飛田成史
  • Organizer: 日本分子イメージング学会
  • Place of Presentation: 学術総合センター
  • Year and Date: 2009-05-15
• [Presentation] 高い細胞膜透過性を示すイリジウム錯体の開発およびin vivo光イメージング
  • Author(s): 吉原利忠, 市川和貴, 穂坂正博, 竹内利行, 飛田成史
  • Organizer: 第33回日本光医学・光生物学会
• [Book] 実験医学増刊Vol. 30 N0. 7, リン光プローブの設計・開発に基づくin vivo低酸素環境イメージング (2012)
  • Author(s): 飛田成史, 吉原利忠, 穂坂正博, 竹内利行
  • Publisher: 羊土社
• [Book] 実験医学増刊Vol.30 No.7 (2012)
  • Author(s): 飛田成史、吉原利忠、穂坂正博、竹内利行
  • Total Pages: 226
  • Publisher: 羊土社
• [Book] Medical Science Digest 35, りん光分子プローブを用いた癌環境イメージング-低酸素の可視化 (2009)
  • Author(s): 飛田成史, 吉原利忠, 穂坂正博, 竹内利行
• [Remarks]
  • URL: http://www.akita-pu.ac.jp/bioresource/dbt/molb/mhosaka/index.html
• [Remarks]
  • URL: http://www.akita-pu.ac.jp/bioresource/dbt/molb/mhosaka/index.html
• [Remarks]
  • URL: http://www.akita-pu.ac.jp/stic/souran/scholar/detail.php?id=270
• [Remarks]
  • URL: http://www.imcr.gunma-u.ac.jp/lab/secbio/
• [Remarks]
  • URL: http://www.imcr.gunma-u.ac.jp/lab/secbio/page5/page5.html
• [Patent(Industrial Property Rights)] 酸素濃度測定試薬および酸素濃度測定方法 (2012)
  • Inventor(s): 飛田成史, 吉原利忠, 竹内利行, 穂坂正博
  • Industrial Property Rights Holder: 群馬大学
  • Acquisition Date: 2012-02-24
• [Patent(Industrial Property Rights)] 新規化合物およびそれを含む機能性プローブ:Novel compound and functionalluminescent probe comprising same (2010)
  • Inventor(s): 飛田成史, 吉原利忠, 穂坂正博, 竹内利行
  • Industrial Property Rights Holder: 群馬大学
  • Filing Date: 2010-04-22
  • Overseas
• [Patent(Industrial Property Rights)] 新規化合物およびそれを含む機能性プローブNovel compound and functional luminescent probe comprising same (2010)
  • Inventor(s): 飛田成史, 吉原利忠, 穂坂正博, 竹内利行
  • Industrial Property Rights Holder: 国立大学法人群馬大学
  • Filing Date: 2010-04-22
  • Overseas