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Head to head comparison of [18F] AV-1451 and [18F] THK5351 for tau imaging in Alzheimer’s disease and frontotemporal dementia

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Abstract

Purpose

Tau accumulation is a core pathologic change in various neurodegenerative diseases including Alzheimer’s disease and frontotemporal lobar degeneration-tau. Recently, tau positron emission tomography tracers such as [18F] AV-1451 and [18F] THK5351 have been developed to detect tau deposition in vivo. In the present study, we performed a head to head comparison of these two tracers in Alzheimer’s disease and frontotemporal dementia cases and aimed to investigate which tracers are better suited to image tau in these disorders.

Methods

A cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We recruited eight participants (two Alzheimer’s disease, four frontotemporal dementia and two normal controls) who underwent magnetic resonance image, amyloid positron emission tomography with [18F]-Florbetaben and tau positron emission tomography with both THK5351 and AV-1451. To measure regional AV1451 and THK5351 uptakes, we used the standardized uptake value ratios by dividing mean activity in target volume of interest by mean activity in the cerebellar hemispheric gray matter.

Results

Although THK5351 and AV-1451 uptakes were highly correlated, cortical uptake of AV-1451 was more striking in Alzheimer’s disease, while cortical uptake of THK5351 was more prominent in frontotemporal dementia. THK5351 showed higher off-target binding than AV-1451 in the white matter, midbrain, thalamus, and basal ganglia.

Conclusions

AV-1451 is more sensitive and specific to Alzheimer’s disease type tau and shows lower off-target binding, while THK5351 may mirror non-specific neurodegeneration.

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Funding

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C2768); and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. NRF-2017R1A2B2005081).

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Authors and Affiliations

  1. Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Kangnam-ku, Seoul, 06351, South Korea

    Young Kyoung Jang, Seongbeom Park, Hee Jin Kim, Hyemin Jang, Duk L. Na & Sang Won Seo

  2. Neuroscience Center, Samsung Medical Center, Seoul, South Korea

    Young Kyoung Jang, Hee Jin Kim, Hyemin Jang, Duk L. Na & Sang Won Seo

  3. Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea

    Chul Hyoung Lyoo & Hanna Cho

  4. Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea

    Seung Jun Oh, Minyoung Oh & Jae Seung Kim

  5. Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea

    Young Hoon Ryu & Jae Yong Choi

  6. Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA

    Gil D. Rabinovici

  7. Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA

    Gil D. Rabinovici & William J. Jagust

  8. Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Seung Hwan Moon

  9. Department of Neurology, Kyung Hee University Hospital, Seoul, South Korea

    Jin San Lee

  10. Center of Functional Imaging, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    William J. Jagust

  11. Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea

    Duk L. Na & Sang Won Seo

  12. Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea

    Sang Won Seo

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  1. Young Kyoung Jang
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  2. Chul Hyoung Lyoo
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Corresponding authors

Correspondence to Jae Seung Kim or Sang Won Seo.

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Conflict of interest

G.D.R. receives research support from Avid Radiopharmaceuticals, Eli Lilly, GE Healthcare and Piramal. He has received consulting fees and speaking honoraria from Eisai, Genentech, Roche, Lundbeck, Putnam and Merck.

Role of the funder

The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Jang, Y.K., Lyoo, C.H., Park, S. et al. Head to head comparison of [18F] AV-1451 and [18F] THK5351 for tau imaging in Alzheimer’s disease and frontotemporal dementia. Eur J Nucl Med Mol Imaging 45, 432–442 (2018). https://doi.org/10.1007/s00259-017-3876-0

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  • DOI: https://doi.org/10.1007/s00259-017-3876-0

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