Development of alpha-synuclein selective PET probe

• Project/Area Number: 25670524
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Tohoku University
• Principal Investigator: OKAMURA Nobuyuki 東北大学, 医学(系)研究科(研究院), 准教授 (40361076)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: αシヌクレイン / パーキンソン病 / PET / バイオマーカー

Outline of Final Research Achievements

Non-invasive detection of α-synuclein deposits would be useful to diagnose Parkinson's diseases accurately as well as to track disease progression. In order to develop a sensitive and selective α-synuclein PET probe, we screened around 160 compounds and found several compounds which show high binding affinity to α-synuclein fibrils. Especially, compound C binds with high affinity to α-synuclein fibrils. Autoradiographic analyses showed that this compound preferentially bound to Lewy bodies in the midbrain sections from patients with Parkinson’s disease. Intravenous administration of this compound further demonstrated sufficient blood-brain barrier permeability in mice. These findings suggest that [18F]compound C is a promising candidate for PETα-synuclein imaging probes.

Research Products

• [Journal Article] Tau PET imaging in Alzheimer’s disease (2014)
  • Author(s): Nobuyuki Okamura, Ryuichi Harada, Shozo Furumoto, Hiroyuki Arai, Kazuhiko Yanai, Yukistsuka Kudo,
  • Journal Title: Current Neurology and Neuroscience Reports Volume: 14 Issue: 11 Pages: 500-500
  • DOI: 10.1007/s11910-014-0500-6
  • Peer Reviewed / Open Access
• [Journal Article] Non-invasive assessment of Alzheimer's disease neurofibrillary pathology using ^<18>F-THK5105 PET (2014)
  • Author(s): Nobuyuki Okamura, Shozo Furumoto, Michelle T. Fodero-Tavoletti, Rachel S. Mulligan, Ryuichi Harada, Paul Yates, Svetlana Pejoska, Yukitsuka Kudo, Colin L. Masters, Kazuhiko Yanai, Christopher C. Rowe, Victor L. Villemagne
  • Journal Title: Brain Volume: 137 Issue: 6 Pages: 1762-1771
  • DOI: 10.1093/brain/awu064
  • Peer Reviewed / Open Access
• [Journal Article] In vivo evaluation of a novel tau imaging tracer for Alzheimer's disease (2014)
  • Author(s): Villemagne L. Victor, Shozo Furumoto, Michelle T. Fodero-Tavoletti, Rachel S. Mulligan, John Hodges, Ryuichi Harada, Paul Yates, Oliver Piguet, Svetlana Pejoska, Vincent Doré, Kazuhiko Yanai, Colin L. Masters, Yukitsuka Kudo, Christopher C. Rowe, Nobuyuki Okamura.
  • Journal Title: European Journal of Nuclear Medicine and Molecular Imaging Volume: 41 Issue: 5 Pages: 816-826
  • DOI: 10.1007/s00259-013-2681-7
  • Peer Reviewed / Open Access
• [Journal Article] Synthesis and preliminary evaluation of 2-arylhydroxyquinoline derivatives for tau imaging (2014)
  • Author(s): Tetsuro Tago, Shozo Furumoto, Nobuyuki Okamura, Ryuichi Harada, Yoichi Ishikawa, Hiroyuki Arai, Kazuhiko Yanai, Ren Iwata, Yhkitsuka Kudo
  • Journal Title: Journal of Labelled Compounds and Radiopharmaceuticals Volume: 57 Issue: 1 Pages: 18-24
  • DOI: 10.1002/jlcr.3133
  • Peer Reviewed
• [Journal Article] Use of a benzimidazole derivative BF-188 in fluorescence multispectral imaging for selective visualization of tau protein fibrils in the Alzheimer's disease brain (2014)
  • Author(s): Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Takeo Yoshikawa, Hiroyuki Arai, Kazuhiko Yanai, Yukitsuka Kudo.
  • Journal Title: Molecular Imaging and Biology Volume: 16 Issue: 1 Pages: 19-27
  • DOI: 10.1007/s11307-013-0667-2
  • Peer Reviewed
• [Journal Article] Analysis of early phase [^(11)C]BF-227 PET , and its application for anatomical standardization of late-phase images for 3D-SSP analysis (2014)
  • Author(s): Kaneta T, Okamura N, Arai A, Takanami K, Furukawa K, Tashiro M, Furumoto S, Iwata R, Takahashi S, Arai H, Y anai K, Kudo Y
  • Journal Title: Jpn J Radiol Volume: 32 Issue: 3 Pages: 138-144
  • DOI: 10.1007/s11604-013-0276-7
  • NAID: 50009030775
  • Peer Reviewed / Open Access
• [Journal Article] Novel ^(11)F-labeled arylquinoline derivatives for non-invasive imaging of tau pathology in Alzheimer' s disease (2013)
  • Author(s): Okamura N, Furumoto S, Harada R, Tago T, Y oshikawa T, Fodero-Tavoletti M, Mulligan RS, Villemagne VL, Akatsu H, Y amamoto T, Arai H, Iwata R, Y anai K, Kudo Y
  • Journal Title: J Nucl Med Volume: 54 Issue: 8 Pages: 1420-1427
  • DOI: 10.2967/jnumed.112.117341
  • Peer Reviewed
• [Journal Article] A ^<18>F-Labeled BF-227 derivative as a potential radioligand for imaging dense amyloid plaques by positron emission tomography (2013)
  • Author(s): Shozo Furumoto
  • Journal Title: Molecular Imaging and Biology Volume: 15 Issue: 4 Pages: 497-506
  • DOI: 10.1007/s11307-012-0608-5
  • Peer Reviewed
• [Journal Article] Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls (2013)
  • Author(s): Maruyama M, Shimada H, Suhara T, Shinotoh H, Ji B, Maeda J, Zhang MR, Trojanowski JQ, Lee VM, Ono M, Masamoto K, Takano H, Sahara N, Iwata N, Okamura N, Furumoto S, Kudo Y, Chang Q, Saido TC, Takashima A, Lewis J, Jang MK, Aoki I, Ito H, Higuchi M.
  • Journal Title: Neuron Volume: 79 Issue: 6 Pages: 1094-1108
  • DOI: 10.1016/j.neuron.2013.07.037
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Recent experiences with THK compounds. (2015)
  • Author(s): Okamura N
  • Organizer: ADPD 2015
  • Place of Presentation: Nice, France
  • Year and Date: 2015-03-17
  • Invited
• [Presentation] Tau and Amyloid Imaging. Outlook for the Future. (2014)
  • Author(s): Okamura N.
  • Organizer: EANM 2014
  • Place of Presentation: Gothenburg, Sweden
  • Year and Date: 2014-10-21
  • Invited
• [Presentation] Tau-Imaging. Results of First-in Human Studies. (2014)
  • Author(s): Okamura N.
  • Organizer: EANM 2014
  • Place of Presentation: Gothenburg, Sweden
  • Year and Date: 2014-10-18
  • Invited
• [Presentation] Imaging neurofibrillary pathology in Alzheimer’s disease using novel tau PET tracer. (2014)
  • Author(s): Okamura N.
  • Organizer: 14th ICGP & 19th JSNP Joint Congress
  • Place of Presentation: つくば国際会議場（つくば市）
  • Year and Date: 2014-10-03
  • Invited
• [Presentation] Advances in Tau PET. (2014)
  • Author(s): Okamura N.
  • Organizer: SNMMI 2014 Annual Meeting
  • Place of Presentation: St. Louis, USA
  • Year and Date: 2014-06-08
  • Invited
• [Presentation] PET imaging of tau deposits in Alzheimer's disease patients using 18F-THK5105 and 18F-THK5117. (2014)
  • Author(s): Okamura N, Furumoto S, Harada R, Furukawa K, Ishiki A, Fodero-Tavoletti MT, Mulligan RS, Iwata R, Tashiro M, Yanai K, Masters CL, Arai H, Rowe CC, Villemagne VL, Kudo Y.
  • Organizer: Human Amyloid Imaging 2014
  • Place of Presentation: Miami, USA
• [Presentation] Tau PET imaging in Alzheimer’s disease using novel 2-phenylquinoline derivatives. (2014)
  • Author(s): Okamura N
  • Organizer: The Fifteenth Conference of Peace through Mind Brain Science
  • Place of Presentation: 浜松
  • Invited
• [Presentation] PET tau imaging in Alzheimer’s disease using 18F-THK5105 and 18F-THK5117. (2014)
  • Author(s): Okamura N, Harada R, Furumoto S, Yanai K, Arai H, Kudo Y.
  • Organizer: The 87th Annual Meeting of The Japanese Pharmacological Society
  • Place of Presentation: 仙台
• [Presentation] PET tau imaging in Alzheimer's disease using novel 18F-labeled 2-phenylquinoline derivatives. (2013)
  • Author(s): Okamura N, Furumoto S, Harada R, Fodero-Tavoletti MT, Mulligan RS, Masters CL, Yanai K, Kudo Y, Rowe CC, Villemagne VL.
  • Organizer: SNMMI Annual Meeting
  • Place of Presentation: Vancouver, Canada
• [Presentation] In vivo detection of tau protein deposits in Alzheimer's disease using 18F-labeled 2-phenylquinoline derivatives. (2013)
  • Author(s): Okamura N, Furumoto S, Harada R, Fodero-Tavoletti MT, Mulligan RS, Masters CL, Yanai K, Kudo Y, Rowe CC, Villemagne VL.
  • Organizer: Alzheimer’s Association International Conference(AAIC) 2013
  • Place of Presentation: Boston, USA
• [Presentation] Imaging prion and other misfolded protein deposits using PET. (2013)
  • Author(s): Okamura N
  • Organizer: Asia Pacific Prion Symposium
  • Place of Presentation: 長崎
  • Invited
• [Presentation] Imaging tau pathology in Alzheimer's disease using 18F-THK5105 and 18F-THK5117 PET (2013)
  • Author(s): Okamura N
  • Organizer: ADNI PPSB meeting
  • Place of Presentation: Washington DC, USA
  • Invited
• [Presentation] PET imaging of tau pathology in patients with Alzheimer's disease using 18F-THK5117. (2013)
  • Author(s): Okamura N, Furumoto S, Harada R, Furukawa K, Ishiki A, Tomita N, Iwata R, Tashiro M, Yanai K, Arai H, Kudo Y.
  • Organizer: Clinical Trials on Alzheimer's Disease 2013
  • Place of Presentation: San Diego, USA