Skip to main content
SpringerLink
Log in

Tau PET in Neurodegenerative Diseases Manifesting Dementia

  • Chapter
  • First Online:
Neuroimaging Diagnosis for Alzheimer's Disease and Other Dementias

  • 2035 Accesses

Abstract

Noninvasive imaging of tau pathology can contribute to the early and differential diagnosis of neurodegenerative diseases and evaluating the efficacy of disease-specific therapies. For in vivo imaging of tau protein deposits in the human brain, PET tracers should exhibit high binding affinity to the β-pleated sheet structure of PHF-tau, high binding selectivity to tau over amyloid-β, and high blood-brain barrier permeability. Several tau PET tracers have been developed and tested in humans. Recent tau PET studies have demonstrated a high amount of tracer retention in sites that have a predilection for the cortical deposition of tau protein aggregates in patients with Alzheimer’s disease (AD). The amount of tracer retention is closely associated with dementia severity and neurodegeneration. Therefore, tau PET is expected to be useful for tracking disease progression, assessing disease severity, and accurately predicting dementia prognosis. In this chapter, we will discuss recent progress in the development of tau-selective PET tracers and clinical PET studies using these tracers.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Villemagne VL, Fodero-Tavoletti MT, Masters CL, Rowe CC. Tau imaging: early progress and future directions. Lancet Neurol. 2015;14(1):114–24. doi:10.1016/S1474-4422(14)70252-2.

    Article  PubMed  Google Scholar 

  2. Ni R, Gillberg PG, Bergfors A, Marutle A, Nordberg A. Amyloid tracers detect multiple binding sites in Alzheimer’s disease brain tissue. Brain. 2013;136:2217–27. doi:10.1093/brain/awt142.

    Article  PubMed  Google Scholar 

  3. Choi SR, Golding G, Zhuang Z, Zhang W, Lim N, Hefti F, Benedum TE, Kilbourn MR, Skovronsky D, Kung HF. Preclinical properties of 18F-AV-45: a PET agent for Abeta plaques in the brain. J Nucl Med. 2009;50:1887–94. doi:10.2967/jnumed.109.065284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Klunk WE, Wang Y, Huang GF, Debnath ML, Holt DP, Shao L, Hamilton RL, Ikonomovic MD, DeKosky ST, Mathis CA. The binding of 2-(4′-methylaminophenyl)benzothiazole to postmortem brain homogenates is dominated by the amyloid component. J Neurosci. 2003;23:2086–92.

    CAS  PubMed  Google Scholar 

  5. Mathis CA, Wang Y, Holt DP, Huang GF, Debnath ML, Klunk WE. Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J Med Chem. 2003;46:2740–54. doi:10.1021/jm030026b.

    Article  CAS  PubMed  Google Scholar 

  6. Villemagne VL, Furumoto S, Fodero-Tavoletti MT, Harada R, Mulligan RS, Kudo Y, Masters CL, Yanai K, Rowe CC, Okamura N. The challenges of tau imaging. Future Neurol. 2012;7:409–21.

    Article  CAS  Google Scholar 

  7. Stankoff B, Freeman L, Aigrot MS, Chardain A, Dolle F, Williams A, Galanaud D, Armand L, Lehericy S, Lubetzki C, Zalc B, Bottlaender M. Imaging central nervous system myelin by positron emission tomography in multiple sclerosis using [methyl-(1)(1)C]-2-(4′-methylaminophenyl)-6-hydroxybenzothiazole. Ann Neurol. 2011;69:673–80. doi:10.1002/ana.22320.

    Article  CAS  PubMed  Google Scholar 

  8. Snellman A, Rokka J, Lopez-Picon FR, Eskola O, Wilson I, Farrar G, Scheinin M, Solin O, Rinne JO, Haaparanta-Solin M. Pharmacokinetics of [18F]flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2012;39:1784–95. doi:10.1007/s00259-012-2178-9.

    Article  CAS  PubMed  Google Scholar 

  9. Dischino DD, Welch MJ, Kilbourn MR, Raichle ME. Relationship between lipophilicity and brain extraction of C-11-labeled radiopharmaceuticals. J Nucl Med. 1983;24:1030–8.

    CAS  Google Scholar 

  10. Agdeppa ED, Kepe V, Liu J, Flores-Torres S, Satyamurthy N, Petric A, Cole GM, Small GW, Huang SC, Barrio JR. Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer’s disease. J Neurosci. 2001;21:RC189.

    CAS  PubMed  Google Scholar 

  11. Shoghi-Jadid K, Small GW, Agdeppa ED, Kepe V, Ercoli LM, Siddarth P, Read S, Satyamurthy N, Petric A, Huang SC, Barrio JR. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry. 2002;10:24–35.

    Article  PubMed  Google Scholar 

  12. Small GW, Kepe V, Ercoli LM, Siddarth P, Bookheimer SY, Miller KJ, Lavretsky H, Burggren AC, Cole GM, Vinters HV, Thompson PM, Huang SC, Satyamurthy N, Phelps ME, Barrio JR. PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med. 2006;355:2652–63. doi:10.1056/NEJMoa054625.

    Article  CAS  PubMed  Google Scholar 

  13. Wolk DA, Price JC, Saxton JA, Snitz BE, James JA, Lopez OL, Aizenstein HJ, Cohen AD, Weissfeld LA, Mathis CA, Klunk WE, De-Kosky ST. Amyloid imaging in mild cognitive impairment subtypes. Ann Neurol. 2009;65:557–68. doi:10.1002/ana.21598.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Nelson LD, Siddarth P, Kepe V, Scheibel KE, Huang SC, Barrio JR, Small GW. Positron emission tomography of brain beta-amyloid and tau levels in adults with down syndrome. Arch Neurol. 2011;68:768–74. doi:10.1001/archneurol.2011.104.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Small GW, Kepe V, Siddarth P, Ercoli LM, Merrill DA, Donoghue N, Bookheimer SY, Martinez J, Omalu B, Bailes J, Barrio JR. PET scanning of brain tau in retired national football league players: preliminary findings. Am J Geriatr Psychiatry. 2013;21:138–44. doi:10.1016/j.jagp.2012.11.019.

    Article  PubMed  Google Scholar 

  16. Kepe V, Bordelon Y, Boxer A, Huang SC, Liu J, Thiede FC, Mazziotta JC, Mendez MF, Donoghue N, Small GW, Barrio JR. PET imaging of neuropathology in tauopathies: progressive supranuclear palsy. J Alzheimers Dis. 2013;36:145–53. doi:10.3233/JAD-130032.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 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. Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron. 2013;79:1094–108. doi:10.1016/j.neuron.2013.07.037.

    Article  CAS  PubMed  Google Scholar 

  18. Hashimoto H, Kawamura K, Igarashi N, Takei M, Fujishiro T, Aihara Y, Shiomi S, Muto M, Ito T, Furutsuka K, Yamasaki T, Yui J, Xie L, Ono M, Hatori A, Nemoto K, Suhara T, Higuchi M, Zhang MR. Radiosynthesis, photoisomerization, biodistribution, and metabolite analysis of 11C-PBB3 as a clinically useful PET probe for imaging of tau pathology. J Nucl Med. 2014;55:1532–8. doi:10.2967/jnumed.114.139550.

    Article  CAS  PubMed  Google Scholar 

  19. Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, Shankle WR, Elizarov A, Kolb HC. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis. 2013;34:457–68. doi:10.3233/JAD-122059.

    CAS  PubMed  Google Scholar 

  20. Xia CF, Arteaga J, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Su H, Szardenings AK, Walsh JC, Wang E, Yu C, Zhang W, Zhao T, Kolb HC. [18F]T807, a novel tau positron emission tomography imaging agent for Alzheimer’s disease. Alzheimers Dement. 2013;9:666–76. doi:10.1016/j.jalz.2012.11.008.

    Article  PubMed  Google Scholar 

  21. Mitsis EM, Riggio S, Kostakoglu L, Dickstein DL, Machac J, Delman B, Goldstein M, Jennings D, D’Antonio E, Martin J, Naidich TP, Aloysi A, Fernandez C, Seibyl J, DeKosky ST, Elder GA, Marek K, Gordon W, Hof PR, Sano M, Gandy S. Tauopathy PET and amyloid PET in the diagnosis of chronic traumatic encephalopathies: studies of a retired NFL player and of a man with FTD and a severe head injury. Transl Psychiatry. 2014;4:e441. doi:10.1038/tp.2014.91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gandy S, DeKosky ST. [18F]-T807 tauopathy PET imaging in chronic traumatic encephalopathy. F1000Res. 2014;3:229. doi:10.12688/f1000research.5372.1.

    PubMed  PubMed Central  Google Scholar 

  23. Chien DT, Szardenings AK, Bahri S, Walsh JC, Mu FR, Xia CF, Shankle WR, Lerner AJ, Su MY, Elizarova A, Kolb HC. Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808. J Alzheimers Dis. 2014;38:171–84. doi:10.3233/Jad-130098.

    PubMed  Google Scholar 

  24. Okamura N, Suemoto T, Furumoto S, Suzuki M, Shimadzu H, Akatsu H, Yamamoto T, Fujiwara H, Nemoto M, Maruyama M, Arai H, Yanai K, Sawada T, Kudo Y. Quinoline and benzimidazole derivatives: candidate probes for in vivo imaging of tau pathology in Alzheimer’s disease. J Neurosci. 2005;25:10857–62. doi:10.1523/JNEUROSCI.1738-05.2005.

  25. Fodero-Tavoletti MT, Okamura N, Furumoto S, Mulligan RS, Connor AR, McLean CA, Cao D, Rigopoulos A, Cartwright GA, O'Keefe G, Gong S, Adlard PA, Barnham KJ, Rowe CC, Masters CL, Kudo Y, Cappai R, Yanai K, Villemagne VL. 18F-THK523: a novel in vivo tau imaging ligand for Alzheimer’s disease. Brain. 2011;134:1089–100. doi:10.1093/brain/awr038.

  26. Harada R, Okamura N, Furumoto S, Tago T, Maruyama M, Higuchi M, Yoshikawa T, Arai H, Iwata R, Kudo Y, Yanai K. Comparison of the binding characteristics of [18F]THK-523 and other amyloid imaging tracers to Alzheimer’s disease pathology. Eur J Nucl Med Mol Imaging. 2013;40:125–32.

    Article  CAS  PubMed  Google Scholar 

  27. Okamura N, Furumoto S, Harada R, Tago T, Yoshikawa T, Fodero-Tavoletti M, Mulligan RS, Villemagne VL, Akatsu H, Yamamoto T, Arai H, Iwata R, Yanai K, Kudo Y. Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease. J Nucl Med. 2013;54:1420–7. doi:10.2967/jnumed.112.117341.

    Article  CAS  PubMed  Google Scholar 

  28. Okamura N, Furumoto S, Fodero-Tavoletti MT, Mulligan RS, Harada R, Yates P, Pejoska S, Kudo Y, Masters CL, Yanai K, Rowe CC, Villemagne VL. Non-invasive assessment of Alzheimer’s disease neurofibrillary pathology using 18F-THK5105 PET. Brain. 2014;137:1762–71. doi:10.1093/brain/awu064.

    Article  PubMed  Google Scholar 

  29. Okamura N, Harada R, Furumoto S, Arai H, Yanai K, Kudo Y. Tau PET imaging in Alzheimer’s disease. Curr Neurol Neurosci Rep. 2014;14:500. doi:10.1007/s11910-014-0500-6.

    Article  PubMed  Google Scholar 

  30. Saito Y, Ruberu NN, Sawabe M, Arai T, Tanaka N, Kakuta Y, Yamanouchi H, Murayama S. Staging of argyrophilic grains: an age-associated tauopathy. J Neuropathol Exp Neurol. 2004;63:911–8.

    Article  PubMed  Google Scholar 

  31. Yamada M, Itoh Y, Sodeyama N, Suematsu N, Otomo E, Matsushita M, Mizusawa H. Senile dementia of the neurofibrillary tangle type: a comparison with Alzheimer’s disease. Dement Geriatr Cogn Disord. 2001;12:117–26.

    Article  CAS  PubMed  Google Scholar 

  32. DeKosky ST, Blennow K, Ikonomovic MD, Gandy S. Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers. Nat Rev Neurol. 2013;9:192–200. doi:10.1038/nrneurol.2013.36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Jack CR Jr. PART and SNAP. Acta Neuropathol. 2014;128:773–6. doi:10.1007/s00401-014-1362-3.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

N. Okamura, S. Furumoto, and Y. Kudo were funded by a grant to study tau PET imaging from GE Healthcare, the SEI (Sumitomo Electric Industries, Ltd.) Group, and the CSR Foundation, as well as by Health and Labor Sciences research grants from the Ministry of Health, Labor, and Welfare of Japan, and a Grant-in-Aid for Exploratory Research (25670524) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan

    Nobuyuki Okamura

  2. Division of Neuro-imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan

    Nobuyuki Okamura, Ryuichi Harada & Yukitsuka Kudo

  3. Frontier Research Institute for Interdisciplinary Science, Tohoku University, Sendai, Miyagi, Japan

    Shozo Furumoto

Authors
  1. Nobuyuki Okamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryuichi Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shozo Furumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yukitsuka Kudo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nobuyuki Okamura .

Editor information

Editors and Affiliations

  1. Integrative Brain Imaging Center, National Center of Neurology & Psychiatry, Kodaira, Tokyo, Japan

    Hiroshi Matsuda

  2. Department of Psychiatry, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Takashi Asada

  3. Department of Diagnostic Radiology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan

    Aya Midori Tokumaru

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Japan

About this chapter

Cite this chapter

Okamura, N., Harada, R., Furumoto, S., Kudo, Y. (2017). Tau PET in Neurodegenerative Diseases Manifesting Dementia. In: Matsuda, H., Asada, T., Tokumaru, A. (eds) Neuroimaging Diagnosis for Alzheimer's Disease and Other Dementias. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55133-1_10

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-55133-1_10

  • Published:

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-55132-4

  • Online ISBN: 978-4-431-55133-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation