Clinical application of tau PET probes

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390297
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• 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): 2011-04-01 – 2014-03-31
• Keywords: 痴呆 / 神経科学 / 放射線 / 脳神経疾患 / 老化

Research Abstract

To detect tau protein deposits in the living brain, [18F]THK-5105 and [18F]THK-5117 have been developed as tau PET probes. In vitro binding assay and autoradiography demonstrated the high binding affinity and selectivity of these probes to tau pathology in Alzheimer's disease (AD) brains. First-in-man PET studies have been performed to assess the clinical usefulness of these probes. AD patients showed THK-5105 and THK-5117 retention in the lateral and medial temporal cortices that are known to contain high density of tau deposits. Regional distribution of these tracers differed considerably from that of PiB. In addition, the retention of these tracers was correlated with clinical severity and brain atrophy in AD patients. From these findings, [18F]THK-5105 and [18F]THK-5117 are considered to be useful for the non-invasive assessment of tau pathology.

Research Products

• [Journal Article] In vivo evaluation of a novel tau imaging tracer for Alzheimer's disease (2014)
  • Author(s): Villemagne VL, Furumoto S, Fodero-Tavoletti MT, Mulligan RS, Hodges J, Harada R, Y ates P, Piguet O, Pejoska S, Doré V, Y anai K, Masters CL, Kudo Y, Rowe CC, Okamura N
  • Journal Title: Eur J Nucl Med Mol Imaging Volume: 41 Pages: 816-826
  • DOI: 10.1007/s00259-013-2681-7
  • 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 Pages: 138-144
  • DOI: 10.1007/s11604-013-0276-7
  • Peer Reviewed
• [Journal Article] Assessing THK523 selectivity for tau deposits in Alzheimer's disease and non-Alzheimer's disease tauopathies (2014)
  • Author(s): Fodero-Tavoletti MT, Furumoto S, Taylor L, McLean CA, Mulligan RS, Birchall I, Harada R, Masters CL, Y anai K, Kudo Y, Rowe CC, Okamura N, Villemagne VL
  • Journal Title: Alzheimers Res Ther Volume: 6 Pages: 11
  • URL: http://alzres.com/content/6/1/11
  • Peer Reviewed
• [Journal Article] Synthesis and preliminary evaluation of 2-arylhydroxyquinoline derivatives for tau imaging (2014)
  • Author(s): Tago T, Furumoto S, Okamura N, Harada R, Ishikawa Y, Arai H, Y anai K, Iwata R, Kudo Y
  • Journal Title: J Labelled Comp Radiopharm Volume: 57 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): Harada R, Okamura N, Furumoto S, Y oshikawa T, Arai H, Y anai K, Kudo Y
  • Journal Title: Mol Imaging Biol Volume: 16 Pages: 19-27
  • DOI: 10.1007/s11307-013-0667-2
  • Peer Reviewed
• [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 Pages: 1420-1427
  • DOI: 10.2967/jnumed.112.117341
  • 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 Pages: 1094-1108
  • DOI: 10.1016/j.neuron.2013.07.037
  • 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): Furumoto S, Okamura N, Furukawa K, Tashiro M, Ishikawa Y, Sugi K, T omita N, Waragai M, Harada R, Tago T, Iwata R, Y anai K, Arai H, Kudo Y
  • Journal Title: Mol Imaging Biol Volume: 15 Pages: 497-506
  • DOI: 10.1007/s11307-012-0608-5
  • Peer Reviewed
• [Journal Article] Evaluation of the biodistribution and radiation dosimetry of the ^(11)F-labelled amyloid imaging probe [^(18)F]F ACT in humans (2013)
  • Author(s): Shidahara M, Tashiro M, Okamura N, Furumoto S, Furukawa K, Watanuki S, Hiraoka K, Miyake M, Iwata R, Tamura H, Arai H, Kudo Y, Y anai K
  • Journal Title: EJNMMI Res Volume: 3 Pages: 32.
  • DOI: 10.1186/2191-219X-3-32
  • Peer Reviewed
• [Journal Article] Comparison of the binding Comparison of the binding (2013)
  • Author(s): Harada R, Okamura N, Furumoto S, Tago T, Maruyama M, Higuchi M, Y oshikawa T, Arai H, Iwata R, Kudo Y, Y anai K
  • Journal Title: Eur J Nucl Med Mol Imaging Volume: 40 Pages: 125-132
  • Peer Reviewed
• [Journal Article] Brain accumulation of amyloid β protein visualized by positron emission tomography and BF-227 in Alzheimer's disease patients with or without diabetes mellitus (2013)
  • Author(s): Tomita N, Furukawa K, Okamura N, Tashiro M, Une K, Furumoto S, Iwata R, Y anai K, Kudo Y, Arai H
  • Journal Title: Geriatr Gerontol Int Volume: 13 Pages: 215-221
  • DOI: 10.1111/j.1447-0594.2012.00880.x
  • Peer Reviewed
• [Journal Article] Cholinergic deficit and response to donepezil therapy in Parkinson's disease with dementia (2012)
  • Author(s): Hiraoka K, Okamura N, Funaki Y, Hayashi A, Tashiro M, Hisanaga K, Fujii T, Takeda A, Y anai K, Iwata R, Mori E
  • Journal Title: Eur Neurol Volume: 68 Pages: 137-143
  • DOI: 10.1159/000338774
  • Peer Reviewed
• [Journal Article] The challenges of tau imaging (2012)
  • Author(s): Villemagne VL, Furumoto S, Fodero-Tavoletti M, Harada R, Mulligan RS, Kudo Y, Masters CL, Y anai K, Rowe CC, Okamura N
  • Journal Title: Future Neurol Volume: 7 Pages: 409-421
  • DOI: 10.2217/fnl.12.34
  • Peer Reviewed
• [Journal Article] Rowe CC. Differential Diagnosis in Alzheimer's Disease and Dementia with Lewy Bodies via VMAT2 and Amyloid Imaging (2012)
  • Author(s): Villemagne VL, Okamura N, Pejoska S, Drago J, Mulligan RS, Chételat G, O'Keefe G, Jones G, Kung HF, Pontecorvo M, Masters CL, Skovronsky DM
  • Journal Title: Neurodegener Dis Volume: 10 Pages: 161-165
  • DOI: 10.1159/000334535
  • Peer Reviewed
• [Journal Article] Synthesis of [^(11)C]interleukin 8 using a cell-free translation system and l-[^(11)C]methionine (2012)
  • Author(s): Harada R, Furumoto S, Y oshikawa T, Ishikawa Y, Shibuya K, Okamura N, Iwata R, Y anai K
  • Journal Title: Nucl Med Biol Volume: 39 Pages: 155-160
  • DOI: 10.1016/j.nucmedbio.2011.07.005
  • Peer Reviewed
• [Journal Article] Cardiac positron-emission tomography images with an amyloid-specific tracer in familial transthyretin-related systemic amyloidosis (2012)
  • Author(s): Furukawa K, Ikeda S, Okamura N, Tashiro M, T omita N, Furumoto S, Iwata R, Y anai K, Kudo Y, Arai H
  • Journal Title: Circulation Volume: 125 Pages: 556-557
  • DOI: 10.1161/CIRCULATIONAHA.111.045237
  • Peer Reviewed
• [Journal Article] Greater responsiveness to donepezil in Alzheimer patients with higher levels of acetylcholinesterase based on attention task scores and a donepezil PET study (2012)
  • Author(s): Kasuya M, Meguro K, Okamura N, Funaki Y, Ishikawa H, Tanaka N, Iwata R, Y anai K
  • Journal Title: Alzheimer Dis Assoc Disord Volume: 26 Pages: 113-118
  • DOI: 10.1097/WAD.0b013e3182222bc0
  • Peer Reviewed
• [Journal Article] A modified method of 3D-SSP analysis for amyloid PET imaging using [^<11>C]BF-227 (2011)
  • Author(s): Kaneta T, Okamura N, Minoshima S, Furukawa K, Tashiro M, Furumoto S, Iwata R, Fukuda H, Takahashi S, Y anai K, Kudo Y, Arai H
  • Journal Title: Ann Nucl Med Volume: 25 Pages: 732-739
  • DOI: 10.1007/s12149-011-0518-7
  • Peer Reviewed
• [Journal Article] [^<18>F]-THK523, a novel in vivo tau imaging ligand for Alzheimer ' s disease (2011)
  • Author(s): Fodero-Tavoletti MT, Okamura N, Furumoto S, Mulligan RS, Connor A, McLean CA, Cao D, Rigopoulos A, O'Keefe G, Gong S, Adlard P A, Barnham KJ, Rowe CC, Masters CL, Kudo Y, Cappai R, Y anai K, Villemagne VL
  • Journal Title: Brain Volume: 134 Pages: 1089-1100
  • DOI: 10.1093/brain/awr038
  • Peer Reviewed
• [Journal Article] Positron emission tomography evaluation of sedative properties of antihistamines (2011)
  • Author(s): Y anai K, Zhang D, Tashiro M, Y oshikawa T, Naganuma F, Harada R, Nakamura T, Shibuya K, Okamura N
  • Journal Title: Expert Opin Drug Saf Volume: 10 Pages: 613-622
  • DOI: 10.1517/14740338.2011.562889
  • Peer Reviewed
• [Journal Article] In vivo assessment of vesicular monoamine transporter type 2 in dementia with Lewy bodies and Alzheimer ' s disease (2011)
  • Author(s): Villemagne VL, Okamura N, Drago J, Pejoska S, Mulligan RS, Chételat G, Ackermann U, O'Keefe G, Jones G, Gong S, T ochon-Danguy H, Kung HF, Pontecorvo MJ, Masters CL, Skovronsky D, Rowe CC
  • Journal Title: Arch Neurol Volume: 68 Pages: 905-912
  • DOI: 10.1001/archneurol.2011.142
  • Peer Reviewed
• [Journal Article] 認知症診断に用いられる検査診断学とバイオマーカー各論BF-227 によるアミロイドイメージング (2011)
  • Author(s): 岡村信行, 原田龍一, 古本祥三, 谷内一彦, 工藤幸司
  • Journal Title: 日本臨床 認知症学(上) Volume: 69(8) Pages: 556-560
  • URL: http://www.nippon-rinsho.co.jp/backnum/z_mokuji/6910ninti1.html
• [Journal Article] アミロイドイメージングの現状と展望 (2011)
  • Author(s): 岡村信行
  • Journal Title: 老年期認知症研究会誌 Volume: 18 Pages: 1-3
  • URL: http://www.rouninken.jp/member/pdf/18_pdf/vol.18_03-18-01.pdf
• [Journal Article] Noninvasive assessment of Alzheimer ' s disease neurofibrillary pathology using ^(18)F-THK5105 PET
  • Author(s): Okamura N, Furumoto S, Fodero-Tavoletti MT, Mulligan RS, Harada R, Y ates P, Pejoska S, Kudo Y, Masters CL, Y anai K, Rowe CC, Villemagne VL
  • Journal Title: Brain Volume: (印刷中)
  • URL: http://brain.oxfordjournals.org/content/early/2014/03/27/brain.awu064.long
  • Peer Reviewed
• [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: Hamamatsu
  • Year and Date: 2014-02-19
• [Presentation] PET imaging of tau deposits in Alzheimer's disease patients using ^<18>F-THK5105 and ^<18>F-THK5117 (2014)
  • Author(s): Okamura N, Furumoto S, Harada R, Furukawa K, Ishiki A, Fodero-Tavoletti MT , Mulligan RS, Iwata R, Tashiro M, Y anai K, Masters CL, Arai H, Rowe CC, Villemagne VL, Kudo Y
  • Organizer: Human Amyloid Imaging 2014
  • Place of Presentation: Miami, USA
  • Year and Date: 2014-01-16
• [Presentation] In vivo detection of tau protein deposits in Alzheimer's disease using ^<18>F-labeled 2-phenylquinoline derivatives (2013)
  • Author(s): Okamura N, Furumoto S, Harada R, Fodero-Tavoletti MT , Mulligan RS, Masters CL, Y anai K, Kudo Y , Rowe CC, Villemagne VL
  • Organizer: Alzheimer ' s Association International Conference 2013
  • Place of Presentation: Boston, USA
  • Year and Date: 20130713-17
• [Presentation] In vivo tau imaging in Alzheimer's disease using [^<18>F]THK-5105 (2013)
  • Author(s): Okamura N, Furumoto S, Harada R, Fodero-Tavoletti MT , Mulligan RS, Masters CL, Y anai K, Kudo Y , Rowe CC, Villemagne VL
  • Organizer: AD/PD The 11th International Conference on Alzheimer's & Parkinson's diseases
  • Place of Presentation: Firenze, Italy
  • Year and Date: 20130305-09
• [Presentation] [^<18>F]THK-5105 and [^<18>F]THK-5117 as possible PET probes for in vivo detection of tau pathology in Alzheimer ' s disease (2013)
  • Author(s): Okamura N, Furumoto S, Harada R, Tago T , Fodero-Tavoletti M, Villemagne VL, Iwata R, Arai H, Y anai K, Kudo Y
  • Organizer: 7th Human Amyloid Imaging meeting
  • Place of Presentation: Miami, USA
  • Year and Date: 20130116-18
• [Presentation] PET imaging of tau pathology in patients with Alzheimer's disease using ^<18>F-THK5117 (2013)
  • Author(s): Okamura N, Furumoto S, Harada R, Furukawa K, Ishiki A, T omita N, Iwata R, Tashiro M, Y anai K, Arai H, Kudo Y
  • Organizer: Clinical Trials on Alzheimer's Disease (CtaD) 2013
  • Place of Presentation: San Diego, USA
  • Year and Date: 2013-11-14
• [Presentation] Imaging tau pathology in Alzheimer's disease using ^<18>F-THK5105 and ^<18>F-THK5117 PET (2013)
  • Author(s): Okamura N
  • Organizer: ADNI PPSB meeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2013-10-26
• [Presentation] PET tau imaging in Alzheimer's disease using novel ^<18>F-labeled 2-phenylquinoline derivatives (2013)
  • Author(s): Okamura N, Furumoto S, Harada R, Fodero-Tavoletti MT , Mulligan RS, Masters CL, Y anai K, Kudo Y , Rowe CC, Villemagne VL
  • Organizer: SNMMI Annual Meeting
  • Place of Presentation: Vancouver , Canada
  • Year and Date: 2013-06-11
• [Presentation] Novel 18F-labeled quinoline derivatives for in vivo detection of tau pathology in Alzheimer ' s disease (2012)
  • Author(s): Okamura N, Furumoto S, Harada R, Fodero-Tavoletti M, Villemagne VL, Iwata R, Y anai K, Kudo Y
  • Organizer: Alzheimer's Association International Conference 2012
  • Place of Presentation: Vancouver , Canada
  • Year and Date: 20120714-19
• [Presentation] [^<11>C]BF-227 PET study in patients with dementia with Lewy bodies (2012)
  • Author(s): Okamura N, Furukawa K, Tashiro M, Furumoto S, Harada R, Arai H, Iwata R, Kudo Y , Yanai K
  • Organizer: SNM2012 annual meeting
  • Place of Presentation: Miami, USA
  • Year and Date: 20120609-12
• [Presentation] Characterization of the binding properties of novel ^<18>F-labeled quinoline derivatives to amyloid and tau protein deposits in Alzheimer ' s disease (2012)
  • Author(s): Okamura N, Furumoto S, Harada R, Tago T , Iwata R, Y anai K, Kudo Y
  • Organizer: The 25th Annual Congress of the European Association of Nuclear Medicine
  • Place of Presentation: Milan, Italy
  • Year and Date: 2012-10-29
• [Presentation] Development of novel tau-specific imaging probes (2012)
  • Author(s): Okamura N
  • Organizer: International Symposium of T ohoku University Molecular Imaging Educational Course
  • Place of Presentation: Sendai
  • Year and Date: 2012-10-04
• [Presentation] Molecular imaging of disease-related pathology in neurodegenerative dementia (2012)
  • Author(s): Okamura N
  • Organizer: The 11th Biennial Meeting of the Asian Pacific Society for Neurochemistry
  • Place of Presentation: Kobe
  • Year and Date: 2012-10-02
• [Presentation] PET tau imaging in Alzheimer ' s disease using ^<18>F-THK5105 and ^<18>F-THK5117 (2012)
  • Author(s): Okamura N, Harada R, Furumoto S, Y anai K, Arai H, Kudo Y
  • Organizer: The 87th Annual Meeting of The Japanese Pharmacological Society
  • Place of Presentation: Sendai
  • Year and Date: 2012-03-21
• [Presentation] Imaging amyloid and tau pathology in Alzheimer ' s disease brain (2012)
  • Author(s): Okamura N
  • Organizer: JSPS-NRF Asian Science Seminar
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2012-02-17
• [Presentation] Noninvasive assessment of drug binding site with positron emission tomography is useful in the prediction of the efficacy of cholinesterase inhibitor (2011)
  • Author(s): Okamura N, Kasuya M, Ishikawa H, Tanaka N, Funaki Y , Iwata R, Meguro K, Y anai K
  • Organizer: 4th Conference Clinical Trials on Alzheimer's Disease
  • Place of Presentation: San Diego, USA
  • Year and Date: 20111103-05
• [Presentation] Phenylquinoline derivatives for in vivo imaging of tau pathology in Alzheimer ' s disease (2011)
  • Author(s): Okamura N, Furumoto S, Harada R, Furukawa K, Arai H, Y anai K, Kudo Y
  • Organizer: 2011 International Conference on Alzheimer's Disease
  • Place of Presentation: Paris, France
  • Year and Date: 2011-07-20
• [Presentation] Near-infrared fluorescence probe X50 for in vivo detection of amyloid plaques in the brain (2011)
  • Author(s): Okamura N, Furumoto S, Harada R, Arai H, Y anai K, Kudo Y
  • Organizer: 2011 International Conference on Alzheimer's Disease
  • Place of Presentation: Paris, France
  • Year and Date: 2011-07-16
• [Book] Annual Review神経 (2012)
  • Author(s): 岡村信行
  • Total Pages: 50-58
  • Publisher: 中外医学社
• [Patent(Industrial Property Rights)] タウイメージングプローブ (2011)
  • Inventor(s): 工藤幸司, 岡村信行, 古本祥三
  • Industrial Property Rights Holder: 国立大学法人東北大学
  • Industrial Property Rights Type: 特許権
  • Industrial Property Number: PCT/JP2011/074930(国際公開番号WO2012/057312)
  • Filing Date: 2011-10-28
  • Overseas