Development of pre-synaptic cholinergic nervous system imaging agent for Alzheimer's disease early diagnosis

• Project/Area Number: 19390316
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: Kanazawa University
• Principal Investigator: SHIBA Kazuhiro Kanazawa University, 学際科学実験センター, 教授 (40143929)
• Co-Investigator(Kenkyū-buntansha): 森 厚文 金沢大学, 学際科学実験センター, 教授 (90019604) ; 小川 数馬 金沢大学, 学際科学実験センター, 助教 (30347471)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2007: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: アセチルコリントランスポーター / 分子イメージング / SPECT / PET / コリン作動性神経 / PFT / コリン作動生神経 / アセチルコリントランスボータ

Research Abstract

We have tried to develop a molecular imaging agent of acethylcholine transporter (VAChT) for Alzheimer's disease early diagnosis, because biochemical changes of the presynaptic cholinergic system have been related to the pathogenesis of Alzheimer's disease. We synthesized (-)-[^<11>C]-methylvesamicol((-)-[^<11>C]OMV) and radioiodinated trans-decalin-o-iodovesamicol(DOIV) as new acetylcholine transporter imaging agents. (-)-[^<11>C]OMV binding in the ipsilateral cortex to the lesion was significantly reduced by 22.0±6.7% compared with that in the contralateral region in kinetics study using disability model monkeys produced by selectively destroying the p75NTR-positive cells in the right hemisphere of the brain. DOIV exhibited in vitro a highest affinity for VAChT among our vesamicol analogs synthesized previously. These results suggested that (-)-[^<11>C]OMV may be useful in the study of dementia characterized by degeneration of the cholinergic neurotransmitter system. Furthermore, radioiodinated DOIV may be superior to (-)-[^<11>C]OMV as VAChT imaging agent.

Research Products

• [Journal Article] The potential of (-)-o-[11C] methyl vesamicol for diagnosing cholinergic deficit dementia. (2009)
  • Author(s): Shiba, K., Nishiyama, S., Tsukada, H., Ishiwata, K., Kawamura, K., Ogawa, K., Mori, H.
  • Journal Title: Synapse Vol.63 Pages: 167-171
  • Peer Reviewed
• [Journal Article] The potential of (-)-o-[11C] methyl vesamicol for diagnosing cholinergic deficit dementia (2009)
  • Author(s): Shiba, K., Nishiyama, S., Tsukada, H., Ishiwata, K., Kawamura, K., Ogawa, K., Mori, H.
  • Journal Title: Synapse Vol.63 Pages: 167-171
  • Peer Reviewed
• [Journal Article] The potential of (-)-o-[11C]methylvesamicol for diagnosing cholinergic deficit dementia (2009)
  • Author(s): Kazuhiro Shiba
  • Journal Title: Synapse 63 Pages: 167-171
  • Peer Reviewed
• [Journal Article] A Change of in Vivo Characteristics Depending on Specific Activity of Radioiodinated (+)-2-[4-(4-iodophenyl) piperidino] cyclohexanol [(+)-pIV] as a Ligand for Sigma Receptor Imaging. (2008)
  • Author(s): Akhter, N., Shiba, K.Ogawa, K., Tsuji, S., Kinuya, S., Nakajima, K, Mori, H.
  • Journal Title: Nucl.Med.Biol. Vol.35 Pages: 29-34
  • Peer Reviewed
• [Journal Article] A Change of in Vivo Characteristics Depending on Specific Activity of Radioiodinated (+)-2-[4-(4-iodophenyl) piperidino] cyclohexanol [(+)-pIV] as a Ligand for Sigma Receptor Imaging (2008)
  • Author(s): Akhter, N., Shiba, K., Ogawa, K., Tsuji, S., Kinuya, S., Nakajima, K, Mori, H.
  • Journal Title: Nucl.Med.Biol. Vol.35 Pages: 29-34
  • Peer Reviewed
• [Journal Article] Rapid Reduction of al-Receptor Binding and 18F-FDG Uptake in Rat Gliomas After In vivo Treatment with Doxorubicine. (2007)
  • Author(s): Waarde, AV., Shiba, K., de Jong, JR., Tshiwata, K., Dierckx, RA, Elsinga, PH.
  • Journal Title: JNucl.Med. Vol.48 Pages: 1320-1326
  • Peer Reviewed
• [Journal Article] Synthesis and evaluation of fluorine -18- labeled SA4503 as a selective sigmal receptor ligand for positron emission tomography. (2007)
  • Author(s): Kawamura, K., Tsukada, H., Shiba, K., Tsuji, C., Harada, N., Kimura, Y, Ishiwata, K.
  • Journal Title: Nucl.Med.Biol. Vol.34 Pages: 571-577
  • Peer Reviewed
• [Journal Article] Rapid Reduction of σ1-Receptor Binding and 18F-FDG Uptake in Rat Gliomas After In vivo Treatment with Doxorubicine (2007)
  • Author(s): Waarde, AV., Shiba, K., de Jong, JR., Ishiwata, K., Dierckx, RA, Elsinga, PH.
  • Journal Title: J Nucl.Med. Vol.48 Pages: 1320-1326
  • NAID: 120007191067
  • Peer Reviewed
• [Journal Article] Synthesis and evaluation of fluorine-18-labeled SA4503 as a selective sigmal receptor ligand for positron emission tomography (2007)
  • Author(s): Kawamura, K., Tsukada, H., Shiba, K., Tsuji, C., Harada, N., Kimura, Y, Ishiwata, K.
  • Journal Title: Nucl.Med.Biol. Vol.34 Pages: 571-577
  • Peer Reviewed
• [Presentation] vesamiool類縁体0^iodo-trans-decalinvesamicol(OIDV)の新規VAChTイメージング剤としての可能性 (2011)
  • Author(s): 小阪孝史
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡県立大学(静岡)
  • Year and Date: 2011-03-30
• [Presentation] 脳の機能及び脳疾患の診断と分子イメージング (2011)
  • Author(s): 柴和弘
  • Organizer: 北陸原子力懇談会
  • Place of Presentation: 金沢都ホテル(石川県)
  • Year and Date: 2011-03-17
• [Presentation] vesamicol類縁体O-iodo-trans-decalinvesamicol(OIDV)の新規VAChTイメージング剤としての可能性 (2011)
  • Author(s): 小坂孝史、鵜野いずみ、北村陽二、小川結加、太田朱音、小川数馬、柴和弘
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡県立大学(静岡県
• [Presentation] PET及びSPECT用インビボ分子イメージング剤の開発研究 (2009)
  • Author(s): 柴和弘
  • Organizer: -脳神経機能の可視化を目指して-
  • Place of Presentation: 富山大学生命科学先端研究センター学術セミナー(富山県)
  • Year and Date: 2009-11-24
• [Presentation] アルツハイマー病の早期診断を目的とした放射性医薬品研究の展望 (2009)
  • Author(s): 柴和弘
  • Organizer: 金沢大学市民公開講座-市民のための放射能・放射線の話-
  • Place of Presentation: 金沢大学サテライトプラザ(石川県)
  • Year and Date: 2009-09-06
• [Presentation] Ligand for vesicular acetylcholine transporter. (2009)
  • Author(s): Shiba.K
  • Organizer: 2009 BIO INTERNATIONAL CONVENTION" (BT02009).
  • Place of Presentation: Georgia World Congress Center (USA)
• [Presentation] Ligand for vesicular acetylcholine transporter (2009)
  • Author(s): Shiba. K
  • Organizer: 2009 BIO INTERNATIONAL CONVENTION" (BIO2009)
  • Place of Presentation: Atlanta (USA)
• [Presentation] Depending on Species Specificity Influence of Difference Metabolic Function in the Biodistribution of Radiolabeled Sigma Ligand as the Tumor Seeking Agent. (2008)
  • Author(s): N.Akhter, K.Shiba, K.Ogawa, S.Tsuji, K.Nakajima, S.Kinuya, H.Mori
  • Organizer: 38th Annual Scientific Meeting of the Australian and New Zealand Society of Nuclear Medicine 2008.
  • Place of Presentation: Conrad Jupiters (Australia)
• [Presentation] Influence of different metabolic function by the species specificity in the biodistribution of radiolabeled sigma ligand as a tumor seeking agent. (2008)
  • Author(s): N.Akhter,K.Shiba, K.Ogawa, S.Tsuji, K.Nakajima, S.Kinuya, H.Mori
  • Organizer: 55th SNM Annual Meeting of the Society of Nuclear Medicine.
  • Place of Presentation: New Orleans Convention Center (USA)
• [Presentation] トランスポーター分子イメージングを利用した脳神経変性疾患の早期診断法に関する研究 (2007)
  • Author(s): 柴和弘
  • Organizer: トランスポーター研究会北陸地方部
  • Place of Presentation: 小杉文化ホール(富山県)
  • Year and Date: 2007-09-29
• [Presentation] トランスポーター分子イメージングを利用した脳神経変性疾患の早期診断法に関する研究 (2007)
  • Author(s): 柴和弘
  • Organizer: トランスポーター研究会北陸地方部
  • Place of Presentation: 射水市(富山県)
  • Year and Date: 2007-09-29
• [Presentation] In-vivo characteristics of high and low specific activity radioiodinated (+)-2-[4-(4-iodophenyl) piperidino] cyclohexanol [(+)-pIV] for imaging sigma-1 receptor in brain. (2007)
  • Author(s): Akhter.N, Shiba.K, K.Ogawa, Kinuya.S, Nakajima.K, Mori.H
  • Organizer: INTERNATIONAL CONFERENCE ON RADIOPHARMACEUTICAL THERAPY (ICRT-2007)
  • Place of Presentation: Ulaanbaatar (Mongolia)
• [Presentation] Potential usefulness of the D2R reorter gene imaging by IBF as a gene therapy monitoring for cerebellar disorder. (2007)
  • Author(s): Shiba.K, K.Ogawa, Torashima.T, Hirai.H, Akhter.N, Kinuya.S, Mori.H
  • Organizer: 54th SNM annual meeting of the Society of Nuclear Medicine.
  • Place of Presentation: Washington Convention Center (USA)
• [Presentation] ^<18>F-labeled SA4503 as a selective sigmal receptor ligand for PET. (2007)
  • Author(s): Kawamura.K, Tsukada.H, Shiba.K, Tsuji.C, Harada.N, Kimura.Y, Ishiwata.K
  • Organizer: A preconference Summer School to BRATN07 and BRATNPET07, under the auspices of the International Society for Cerebral Blood Flow and Metabolism.
  • Place of Presentation: Translational Research Informatics Center (Hyogo)
• [Presentation] In-vivo characteristics of high and low specific activity radioiodinated (+)-2-[4-(4-iodophenyl) piperidino] cyclohexanol [(+)-pIV] for imaging sigma-1 receptor in brain (2007)
  • Author(s): Akhter. N, Shiba. K, Ogaw. K, Kinuya. S, Nakajima. K, Mori. H
  • Organizer: INTERNATIONAL CONFERENCE ON RADIOPHARMACEUTICAL THERAPY (ICRT-2007)
  • Place of Presentation: Ulaanbaatar (Mongolia)
• [Presentation] Potential usefulness of the D2R reorter gene imaging by IBF as a gene therapy monitoring for cerebellar disorder (2007)
  • Author(s): Shiba. K, Ogawa. K, Torashima. T, Hirai. H, Akhter. N, Kinuya. S, Mori. H
  • Organizer: 54th SNM annual meeting of the Society of Nuclear Medicine
  • Place of Presentation: Washington DC (USA)
• [Presentation] ^<18>F-labeled SA4503 as a selective sigmal receptor ligand for PET (2007)
  • Author(s): Kawamura. K, Tsukada. H, Shiba. K, Tsuji. C, Harada. N, Kimura. Y, Ishiwata. K
  • Organizer: A preconference Summer School to BRAIN07 and BRAINPET07, under the auspices of the International Society for Cerebral Blood Flow and Metabolism
  • Place of Presentation: Kobe (Japan)