Development of the Colin transporter imaging agent for early diagnosis of Alzheimer's disease

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591813
• 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: SHIBA Kazuhiro 金沢大学, 学際科学実験センター, 教授 (40143929)
• Co-Investigator(Kenkyū-buntansha): KITAMURA Yoji 金沢大学, 学際科学実験センター, 准教授 (10368483) ; KOZAKA Takashi 金沢大学, 学際科学実験センター, 助教 (50579836)
• Project Period (FY): 2011 – 2013
• Keywords: アルツハイマー病 / コリン作動性神経 / 分子イメージング / アセチルコリントランスポーター / SPECT

Research Abstract

We aimed at the development of the imaging probe for early diagnosis of Alzheimer's disease (AD). The cognitive impairment of AD is related to the cholinergic nerve system. we targeted the cholin transporter(ChT) and the acetylcholine transporter(VAChT) which exist in pre-synapse in cholinergic nerve. We synthesized the imaging probes with high affinity for ChT or VAChT. We could not develope a probe with high affinity for ChT in in vitro assays. However, I could synthesize a probe with high affinity for VAChT such as (-)-o-iododecalinvesamicol(OIDV). Radioiodinated OIDV ((-)-[I-125]OIDV) accumulated in rat brain through B.B.B. In vivo blocking and ex vivo autoradiography study showed that (-)-[I-125]OIDV selevtively accumulated in the VAChT in rat brain. These results showed that (-)-[I-125]OIDV bound selectively to VAChT in rat brain in vivo. Radioiodinated (-)-OIDV labeled with I-123 was suggested to be useful as a VAChT imaging agent for SPECT.

Research Products

• [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 Pages: 107-113
  • DOI: 10.1002/syn.21720
  • 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 Pages: 4936-4941
  • DOI: 10.1016/j.bmc.2012.06.040
  • Peer Reviewed
• [Presentation] Evaluation of radiolabeled o-bromo- decalinvesamicol (OBDV) as a PET ligand for the Vesicular Acetylcholine Transporter (VAChT) (2014)
  • Author(s): Azim, MA., Kozaka, T., Uno, I., Miwa, D., Kitamura, Y., Ogawa, K., Kawai, K., Makino, A., Kiyono, Y and Shiba, K
  • Organizer: International Workshop on Molecular Functional Imaging for Brain and Gynecologic Oncology
  • Place of Presentation: ユアーズホテルフクイ(福井市)
  • Year and Date: 20140303-04
• [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[^<11>C]OMDVの開発 (2013)
  • Author(s): 三輪大輔,小阪孝史,鵜野いずみ,北村陽二, Azim Mohammad A.,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(静岡市)
  • Year and Date: 20130829-30
• [Presentation] VAChTイメージング用[^<125>I]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、Azim Mohammad A、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(静岡市)
  • Year and Date: 20130829-30
• [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. Vancouber Convention Centre
  • Place of Presentation: Vancouber, BC, Canada
  • Year and Date: 20130608-12
• [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
  • Year and Date: 20130608-12
• [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[^<11>C]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 Anwer-ul AZIM,川村和紀、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、横浜市
  • Year and Date: 20130327-30
• [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 Anwer-ul AZIM,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、横浜市
  • Year and Date: 20130327-30
• [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、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・学術大会
  • Place of Presentation: アクトシティ浜松(浜松市)
  • Year and Date: 20120524-25
• [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,Azim Mohammad Anwar-ul,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,京都市
  • Year and Date: 2012-12-15
• [Presentation] VAChTイメージング用新規プローブの合成とその評価 (2011)
  • Author(s): 鵜野いずみ,小阪孝史,北村陽二,小川数馬,川井恵一,絹谷清剛,柴和弘
  • Organizer: 第11回放射性医薬品・画像診断薬研究会
  • Place of Presentation: 京都市
  • Year and Date: 2011-12-03
• [Presentation] Vesamicol誘導体を用いた新規VAChTイメージング剤の開発 (2011)
  • Author(s): 小阪孝史,鵜野いずみ,北村陽二,小川数馬,川井恵一,絹谷清剛,柴和弘
  • Organizer: 第51回日本核医学会学術総会
  • Place of Presentation: 筑波市
  • Year and Date: 2011-10-29