Development and application of radiometal-octabromoporphyrin as a tumor imaging agent

• Project/Area Number: 24591812
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Kanazawa University
• Principal Investigator: KITAMURA Yoji 金沢大学, 学際科学実験センター, 准教授 (10368483)
• Co-Investigator(Kenkyū-buntansha): OGAWA Kazuma 金沢大学, 新学術創成研究機構, 准教授 (30347471)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 放射性医薬品 / ポルフィリン / 腫瘍 / 錯体

Outline of Final Research Achievements

In this study, a new radiometal-octabromoporphyrines was developed and the possibililty of application for a new tumor imaging agent was examined. As a result, it was found that Octabromotetrakis (4-carboxyphenyl)porphine（OBTCPP） could be radiolabelled by 111In, a radio nuclear for diagnosis, in short times. It was also found that, in tumor bearing mice which transplanted NB2a tumor cell or KLN205 tumor cell, 111In-OBTCPP was accumulated in both tumors at about 4% dose/g, and tumor to muscle ratio was over 10 in the tumors.

Research Products

• [Journal Article] Design, synthesis and biological evaluation of negatively charged 111In-DTPA-octreotide derivatives (2014)
  • Author(s): Oshima N, Akizawa H, Zhao S, Nishijima K, Kitamura Y, Arano Y, Kuge Y, Ohkura K
  • Journal Title: Bioorgan Med Chem Volume: 22 Issue: 4 Pages: 1377-1382
  • DOI: 10.1016/j.bmc.2013.12.063
  • Peer Reviewed
• [Journal Article] Anxiety- and depression-like behavior in mice lacking the CD157/BST1 gene, a risk factor for Parkinson's disease. (2014)
  • Author(s): Lopatina O, Yoshihara T, Nishimura T, Zhong J, Akther S, Fakhrul AA, Liang M, Higashida C, Sumi K, Furuhara K, Inahata Y, Huang JJ, Koizumi K, Yokoyama S, Tsuji T, Petugina Y, Sumarokov A, Salmina AB, Hashida K, Kitao Y, Hori O, Asano M, Kitamura Y, Kozaka T, Shiba K, Zhong F, Xie MJ, Sato M, Ishihara K, Higashida H.
  • Journal Title: Front Behav Neurosci Volume: 8 Pages: 1-18
  • DOI: 10.3389/fnbeh.2014.00133
  • Peer Reviewed / Open Access
• [Journal Article] The potential of o-bromo-trans-decalinvesamicol as a new PET ligand for vesicular acetylcholine transporter imaging. (2014)
  • Author(s): Azim M. A.-u., Kozaka T., Uno I., Miwa D., Kitamura Y., Ogawa K., Makino A., Kiyono Y. and Shiba K.
  • Journal Title: Synapse Volume: 68 Issue: 10 Pages: 445-453
  • DOI: 10.1002/syn.21756
  • Peer Reviewed
• [Journal Article] Regional brain imaging of vesicular acetylcholine transporter (VAChT) using o-[^<12>5I]iodo-trans-decalin vesamicol as a new potential imaging probe (2014)
  • Author(s): Kozaka, T., Uno, I., Kitamura, Y., Miwa, D., Azim,MA., Ogawa, K. Shiba. K
  • Journal Title: Synapse Volume: Vol. 68 Issue: 3 Pages: 107-113
  • DOI: 10.1002/syn.21720
  • Peer Reviewed
• [Journal Article] Decontamination of radioactivity from contaminated vegetables derived from the Fukushima nuclear accident. (2013)
  • Author(s): Shiba K., Kitamura Y., Kozaka T., Uno I., Shimizu K., Masumoto K., Hirota M., Higaki S., Miyoshi H., Saze T., Sakama M. and Yanaga M.
  • Journal Title: Radiation Measurements Volume: 55 Pages: 26-29
  • DOI: 10.1016/j.radmeas.2013.01.010
  • Peer Reviewed
• [Journal Article] Development and evaluation of a novel (99m)tc-labeled annexin A5 for early detection of response to chemotherapy (2013)
  • Author(s): Ogawa, K. Ohtsuki, K. Shibata, T. Aoki, M. Nakayama, M. Kitamura, Y. Ono, M. Ueda, M. Doue, T. Onoguchi, M. Shiba, K. Odani, A.
  • Journal Title: PLoS One Volume: 8 Issue: 12 Pages: e81191-e81191
  • DOI: 10.1371/journal.pone.0081191
  • NAID: 120006986751
  • Peer Reviewed
• [Journal Article] Development and evaluation of a radiobromine-labeled sigma ligand for tumor imaging. (2013)
  • Author(s): Ogawa K., Kanbara H., Kiyono Y., Kitamura Y., Kiwada T., Kozaka T., Kitamura M., Mori T., Shiba K. and Odani A.
  • Journal Title: Nuclear Medicine and Biology Volume: 40 Issue: 4 Pages: 445-450
  • DOI: 10.1016/j.nucmedbio.2013.02.008
  • Peer Reviewed
• [Journal Article] Development of Novel Radiogallium-Labeled Bone Imaging Agents Using Oligo-Aspartic Acid Peptides as Carriers. (2013)
  • Author(s): Ogawa K., Ishizaki A., Takai K., Kitamura Y., Kiwada T., Shiba K. and Odani A.
  • Journal Title: PLoS ONE Volume: 8 Issue: 12 Pages: e84335-e84335
  • DOI: 10.1371/journal.pone.0084335
  • NAID: 120007185665
  • Peer Reviewed
• [Journal Article] Development of New Zinc Dithiosemicarbazone Complex for Use as Oral Antidiabetic Agent. (2013)
  • Author(s): Kadowaki S., Munekane M., Kitamura Y., Hiromura M., Kamino S., Yoshikawa Y., Saji H. and Enomoto S.
  • Journal Title: Biological Trace Element Research Volume: 154 Issue: 1 Pages: 111-119
  • DOI: 10.1007/s12011-013-9704-x
  • Peer Reviewed
• [Journal Article] Characteristics of radioactive contamination of vegetables derived from the Fukushima nuclear accident (2012)
  • Author(s): Shiba K., Kitamura Y., Kozaka T., Uno I., Shimizu K., Hirota M., Higaki S. and Masumoto K.
  • Journal Title: Radiation Safety Management Volume: 11 Issue: 1 Pages: 19-22
  • DOI: 10.12950/rsm.11.19
  • NAID: 130002581100
  • ISSN: 1347-1511, 1884-9520
  • Peer Reviewed
• [Journal Article] Chemical removal of radionuclides in contaminated spinach derived from the Fukushima nuclear accident (2012)
  • Author(s): Shiba K., Kitamura Y., Kozaka T., Uno I., Miyoshi H., Yanaga M.
  • Journal Title: Radiation Safety Management Volume: 11 Issue: 1 Pages: 23-26
  • DOI: 10.12950/rsm.11.23
  • NAID: 130002581101
  • ISSN: 1347-1511, 1884-9520
  • Peer Reviewed
• [Journal Article] Development and evaluation of a novel radioiodinated vesamicol analog as a sigma receptor imaging agent. (2012)
  • Author(s): Ogawa K., Kanbara H., Shiba K., Kitamura Y., Kozaka T., Kiwada T. and Odani A.
  • Journal Title: EJNMMI Research Volume: 2 Issue: 1 Pages: 54-63
  • DOI: 10.1186/2191-219x-2-54
  • NAID: 120007186978
  • Peer Reviewed
• [Journal Article] Syntheses and in vitro evaluation of decalinvesamicol analogues as potential imaging probes for vesicular acetylcholine transporter (VAChT) (2012)
  • Author(s): Kozaka, T., Uno, I., Kitamura, Y., Miwa, D., Ogawa, K., Shiba, K
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: Vol.20 Issue: 16 Pages: 4936-4941
  • DOI: 10.1016/j.bmc.2012.06.040
  • Peer Reviewed
• [Presentation] [111In-DTPA-D-Phe-1-Asp0-D-Phe1]-オクトレオチドの体内動態評価: 放射能の腎集積性低減と腫瘍集積性の向上 (2015)
  • Author(s): 大島伸宏, 秋澤宏行, 河嶋秀和, 趙松吉, 趙芫, 西嶋剣一, 北村陽二, 荒野泰, 久下裕司, 大倉一枝
  • Organizer: 日本薬学会 第135年会
  • Place of Presentation: 神戸学院大学，兵庫県
  • Year and Date: 2015-03-28
• [Presentation] 15q重複モデルマウスにおける脳内ドーパミン神経系の変化 (2015)
  • Author(s): 黒宮里紗, 菅谷望, 北村陽二, 三輪大輔, 小阪孝史, 小川数馬, 内匠透, 柴和弘
  • Organizer: 日本薬学会 第135年会
  • Place of Presentation: 神戸サンボーホール，兵庫県
  • Year and Date: 2015-03-28
• [Presentation] 新規vesamicol類縁体PIDVのσ-2受容体イメージング剤としての可能性 (2015)
  • Author(s): 小阪孝史, 緩詰沙耶, 三輪大輔, 北村陽二, Mohammad A. AZIM, 小川数馬, 川井恵一, 柴 和弘
  • Organizer: 日本薬学会 第135年会
  • Place of Presentation: 神戸サンボーホール，兵庫県
  • Year and Date: 2015-03-27
• [Presentation] 光学活性体(-)-[11C]OMDVのVAChTイメージング剤としての評価 (2015)
  • Author(s): 小阪孝史, 茂野泰貴, 三輪大輔, 北村陽二, Mohammad A. AZIM, 小川数馬, 川井恵一, 柴和弘
  • Organizer: 日本薬学会 第135年会
  • Place of Presentation: 神戸サンボーホール，兵庫県
  • Year and Date: 2015-03-27
• [Presentation] SPECT用σ-2受容体イメージング剤の合成と基礎的評価 (2014)
  • Author(s): 小阪孝史、緩詰沙耶、三輪大輔、Mohammad A. Azim、黒宮里紗、北村陽二、小川数馬、川井恵一、柴 和弘
  • Organizer: 第54回日本核医学会学術総会
  • Place of Presentation: 大阪国際会議場，大阪府
  • Year and Date: 2014-11-05 – 2014-11-08
• [Presentation] PET用イメージング剤[11C]OMDVの光学分割と動態評価 (2014)
  • Author(s): 三輪大輔、小阪孝史、北村陽二、Mohammad A. Azim、黒宮里紗、緩詰沙耶、小川数馬、川井恵一、柴 和弘
  • Organizer: 第54回日本核医学会学術総会
  • Place of Presentation: 大阪国際会議場，大阪府
  • Year and Date: 2014-11-05 – 2014-11-08
• [Presentation] 放射性金属-八臭素化ポルフィリン誘導体の腫瘍診断薬としての検討 (2014)
  • Author(s): 北村陽二、小川数馬、小阪孝史、中島美由紀、Mohammad A. Azim、三輪大輔、黒宮里紗、緩詰沙耶、柴 和弘
  • Organizer: 第25回 日本微量元素学会学術集会
  • Place of Presentation: 岡山大学，岡山県
  • Year and Date: 2014-07-03 – 2014-07-04
• [Presentation] Study of radiomeal-octabromoporphyrin complex as a tumor diagnostic agent (2014)
  • Author(s): Yoji KITAMURA, Kazuma OGAWA, Takashi KOZAKA, Miyuki NAKASHIMA, Mohammad A. Azim, Daisuke MIWA, Risa KUROMIYA, Saya YURUZUME, and Kazuhiro SHIBA
  • Organizer: 第24回金属の関与する生体関連反応シンポジウムSRM2014
  • Place of Presentation: 京都薬科大学，京都府
  • Year and Date: 2014-06-14 – 2014-06-15
• [Presentation] Introduction of radiobromine labeled decalinvesamicol analogue as a new and promising PET vesicular acetylcholine transporter (VAChT) imaging probe. (2014)
  • Author(s): Azim Anwar-ul, Takashi Kozaka, Izumi Uno, Daisuke Miwa, Yoji Kitamura, Kazuma Ogawa, Keiichi Kawai, Yasushi Kiyono, and Kazuhiro Shiba
  • Organizer: 2014 SNMMI 61th annual meeting
  • Place of Presentation: St. Louis Convention Center, ST. LOUIS, MISSOURI, USA.
  • Year and Date: 2014-06-07 – 2014-06-11
• [Presentation] σ-2受容体イメージング剤PIDVの開発研究 (2014)
  • Author(s): 小阪孝史、緩詰沙耶、三輪大輔、鵜野いずみ、Mohammad A. Azim、北村陽二、小川数馬、川井恵一、柴 和弘
  • Organizer: 第9回日本分子イメージング学会総会・学術集会
  • Place of Presentation: 千里ライフサイエンスセンター，大阪府
  • Year and Date: 2014-05-22 – 2014-05-23
• [Presentation] Evaluation of Radiolabeled o-Bromo-decalinvesamicol (OBDV) as a PET Ligand for the Vesicular Acetylcholine Transporter (VAChT) (2014)
  • Author(s): Azim Mohammad Anwar-ul，Takashi Kozaka，Izumi Uno，Daisuke Miwa，Yoji Kitamura，Kazuma Ogawa，Keiichi Kawai，Akira Makino，Yasushi Kiyono，Kazuhiro Shiba
  • Organizer: International Workshop for Molecular Functional Imaging -Brain and Gynecologic Oncology-(Fukui2014: The Fifth International Workshop on Biomedical Imaging)
  • Place of Presentation: ユアーズホテルフクイ，福井県
• [Presentation] A new and promising VAChT imaging probe for PET: Radiobromine labeled analogue of decalinvesamicol (2014)
  • Author(s): Azim Mohammad Anwar-ul，小阪 孝史，鵜野 いずみ，三輪 大輔，北村 陽二，小川 数馬，川井 恵一，清野 泰，柴 和弘
  • Organizer: 日本薬学会 第134年会
  • Place of Presentation: 熊本大学，熊本県
• [Presentation] 生理活性放射性金属キレート化合物 (2014)
  • Author(s): 北村 陽二
  • Organizer: 日本薬学会 第134年会
  • Place of Presentation: 熊本大学，熊本県
  • Invited
• [Presentation] Syntheses and in vitro evaluation of OBBV as a potential σ-1 receptor imaging probe (2013)
  • Author(s): Mohammad Anwar-Ul Azim，小阪孝史，鵜野いずみ，三輪大輔，北村陽二，小川数馬，絹谷清剛，川井恵一，柴 和弘
  • Organizer: 第8回日本分子イメージング学会総会・学術集会
  • Place of Presentation: 横浜赤レンガ倉庫1号館，神奈川県
• [Presentation] 111In標識八臭素化ポルフィリン誘導体の腫瘍診断薬としての検討 (2013)
  • Author(s): 北村陽二，小川数馬，小阪孝史，Mohammad Anwar-Ul Azim，鵜野いずみ，三輪大輔，中島美由紀，御舩正樹，斎藤 寛，榎本秀一，柴 和弘
  • Organizer: 第8回日本分子イメージング学会総会・学術集会
  • Place of Presentation: 横浜赤レンガ倉庫1号館，神奈川県
• [Presentation] In vivo evaluation of radioiodinated o-iodo-trans-decalinvesamicol(OIDV) as a vesicular acetylcholine transporter (VAChT) imaging agent. (2013)
  • Author(s): Uno I, Kozaka T, Kitamura Y, Miwa D, Azim MA, Ogawa K, Kawai K, Taki J, Kinuya S, Shiba K.
  • Organizer: 2013 SNMMI 60th annual meeting
  • Place of Presentation: Vancouber Convention Centre, Vancouber, BC, Canada.
• [Presentation] The development of potential vesicular acetylcholine transporter (VAChT) PET imaging probes. (2013)
  • Author(s): Kozaka T, Miwa D, Uno I, Kitamura Y, Azim MA, Ogawa K, Kinuya S, Kawai K, Shiba K.
  • Organizer: 2013 SNMMI 60th annual meeting
  • Place of Presentation: Vancouber Convention Centre, Vancouber, BC, Canada.
• [Presentation] In vivo evaluation of radiomeal-octabromoporphyrin complex as a tumor imaging agent (2013)
  • Author(s): Yoji Kitamura, Kazuma Ogawa, Takashi Kozaka, Mohammad A. Azim, Izumi Uno, Daisuke Miwa, Narumi Nishimura, Kaname Hatakenaka, Miyuki Nakashima, Masaki Mifune, Yutaka Saito, Shuichi Enomoto, and Kazuhiro Shiba
  • Organizer: 第23回金属の関与する生体関連反応シンポジウムSRM2013
  • Place of Presentation: 武蔵野大学，東京都
• [Presentation] 脳内小胞アセチルコリントランスポーター（VAChT）のPETイメージングプローブ[11C]OMDVの開発 (2013)
  • Author(s): 三輪 大輔，小阪孝史，鵜野いずみ，北村陽二，Mohammad A. Azim，河村和紀，小川数馬，川井恵一，柴 和弘
  • Organizer: 第11回次世代を担う若手のためのフィジカル・ファーマフォーラム
  • Place of Presentation: 清水テルサおよび三保園ホテル，静岡県
• [Presentation] VAChTイメージング用[125I]OIDVのジアステレオマー分離と in vivo 脳内動態変化 (2013)
  • Author(s): 鵜野 いずみ，小阪 孝史，三輪 大輔，北村 陽二，Mohammad A. Azim，小川 数馬，川井 恵一，柴 和弘
  • Organizer: 第11回次世代を担う若手のためのフィジカル・ファーマフォーラム
  • Place of Presentation: 清水テルサおよび三保園ホテル，静岡県
• [Presentation] 骨指向性放射性ガリウム標識薬剤の開発研究 (2013)
  • Author(s): 石﨑淳志，小川数馬，高井健一郎，北村陽二，黄檗達人，柴和弘, 小谷明
  • Organizer: 第11回次世代を担う若手のためのフィジカル・ファーマフォーラム
  • Place of Presentation: 清水テルサおよび三保園ホテル，静岡県
• [Presentation] In vivo evaluation of radiobromine-labeled o-bromo-trans-decalinvesamicol (OBDV) as a potential VAChT imaging probe (2013)
  • Author(s): Azim Mohammad Anwar-ul，小阪孝史，鵜野いずみ，三輪大輔，北村陽二，小川数馬，川井恵一，清野 泰，柴 和弘
  • Organizer: 第１３回放射性医薬品・画像診断薬研究会
  • Place of Presentation: 京都ガーデンパレス，京都府
• [Presentation] アルツハイマー病の早期診断を目的とした新規PET用VAChTイメージング剤[11C]OMDVの合成とin vivo評価 (2013)
  • Author(s): 小阪孝史，三輪大輔，鵜野いずみ，北村陽二，Mohammad Anwar-ul AZIMl，河村和紀，小川数馬，川井恵一，柴 和弘
  • Organizer: 日本薬学会 第133年会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] OIDVのジアステレオマー分離とその選択的VAChTイメージング剤としての評価 (2013)
  • Author(s): 鵜野いずみ，小阪孝史，三輪大輔，北村陽二，Mohammad Anwar-ul AZIMl，小川数馬，川井恵一，河原栄，柴 和弘
  • Organizer: 日本薬学会 第133年会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] PET 用VAChT イメージング剤の開発研究 (2012)
  • Author(s): 小阪孝史，三輪大輔，鵜野いずみ，北村陽二，Mohammad Anwar-ul AZIMl，小川数馬，川井恵一，絹谷清剛，柴 和弘
  • Organizer: 第１２回放射性医薬品・画像診断薬研究会
  • Place of Presentation: 京都テルサ（京都）
• [Presentation] アスパラギン酸で負電荷を導入した 111In-DTPA-D-Phe1-オクトレオチド誘導体の in vitro 腫瘍集積性および体内動態の評価 (2012)
  • Author(s): 大島 伸宏，秋澤 宏行，趙 松吉，趙 芫，西嶋 剣一，北村 陽二，荒野 泰，久下 裕司，大倉 一枝
  • Organizer: 日本薬学会北海道支部第 139 回例会
  • Place of Presentation: 北海道大学 学術交流会館（北海道）
• [Presentation] Evaluation of 99mTc-labeled Annexin A5 using a bis(hydroxamamide) derivative for detection of tumor response to therapy (2012)
  • Author(s): Kazuma Ogawa，Tomomi Shibata，Yoji Kitamura，Tatsuto Kiwada，Morio Nakayama，Kazuhiro Shiba，Akira Odani
  • Organizer: Society of Nuclear Medicine 59th Annual Meeting
  • Place of Presentation: Miami Beach Convention Center (USA)
• [Presentation] Study on a radiomeal-octabromoporphyrin complex as a tumor imaging agent (2012)
  • Author(s): Yoji Kitamura, Takako Shimizu, Asana Tatsumi, Kazuma Ogawa, Takashi Kozaka, et. al.
  • Organizer: 第22回金属の関与する生体関連反応シンポジウムSRM2012
  • Place of Presentation: 金沢大学（石川県）
• [Presentation] 前シナプスコリン作動性神経描画用新規VAChTイメージング剤の開発 (2012)
  • Author(s): 鵜野いずみ，小阪孝史，三輪大輔，北村陽二，道関美祐希，小川数馬，川井恵一，河原 栄，柴 和弘
  • Organizer: 第7回日本分子イメージング学会総会・学術集会
  • Place of Presentation: アクトシティ浜松（静岡県）
• [Presentation] N末端構造を変換した111In-DOTA-octreotide の体内動態に関する検討 (2012)
  • Author(s): 竹中文章，北村陽二，神野伸一郎，秋澤宏行，荒野 泰，榎本秀一
  • Organizer: 第7回日本分子イメージング学会総会・学術集会
  • Place of Presentation: アクトシティ浜松（静岡県）