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[18F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer’s disease

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Visualization of the spatial distribution of neurofibrillary tangles would help in the diagnosis, prevention and treatment of dementia. The purpose of the study was to evaluate the clinical utility of [18F]THK-5117 as a highly selective tau imaging radiotracer.

Methods

We initially evaluated in vitro binding of [3H]THK-5117 in post-mortem brain tissues from patients with Alzheimer’s disease (AD). In clinical PET studies, [18F]THK-5117 retention in eight patients with AD was compared with that in six healthy elderly controls. Ten subjects underwent an additional [11C]PiB PET scan within 2 weeks.

Results

In post-mortem brain samples, THK-5117 bound selectively to neurofibrillary deposits, which differed from the binding target of PiB. In clinical PET studies, [18F]THK-5117 binding in the temporal lobe clearly distinguished patients with AD from healthy elderly subjects. Compared with [11C]PiB, [18F]THK-5117 retention was higher in the medial temporal cortex.

Conclusion

These findings suggest that [18F]THK-5117 provides regional information on neurofibrillary pathology in living subjects.

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Compliance with Ethical Standards

Funding

This study was supported by the research fund from GE Healthcare, the SEI (Sumitomo Electric Industries, Ltd.) Group CSR Foundation, the Industrial Technology Research Grant Program of the NEDO in Japan (09E51025a), Health and Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare of Japan, a Grant-in-Aid for Scientific Research (B) (23390297), a Grant-in-Aid for Scientific Research on Innovative Areas (26117003) and “Japan Advanced Molecular Imaging Program (J-AMP)” of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.

Conflicts of interest

Yukitsuka Kudo, Nobuyuki Okamura and Shozo Furumoto received research grants from GE Healthcare. Yukitsuka Kudo also received research grants from Sumitomo Electric Industries. Yukitsuka Kudo and Nobuyuki Okamura own stock in Clino Ltd.

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. This article does not contain any studies with animals performed by any of the authors.

Informed consent

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

Author information

Authors and Affiliations

  1. Division of Neuro-imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-8575, Japan

    Ryuichi Harada, Nobuyuki Okamura & Yukitsuka Kudo

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

    Nobuyuki Okamura, Takeo Yoshikawa & Kazuhiko Yanai

  3. Frontier Research Institute for Interdisciplinary Science, Tohoku University, Sendai, 980-8578, Japan

    Shozo Furumoto

  4. Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, 980-8578, xJapan

    Shozo Furumoto, Yoichi Ishikawa, Tetsuro Tago, Yoshihito Funaki, Ren Iwata & Yukitsuka Kudo

  5. Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-8575, Japan

    Katsutoshi Furukawa, Aiko Ishiki, Naoki Tomita & Hiroyuki Arai

  6. Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, 980-8578, Japan

    Kotaro Hiraoka, Shoichi Watanuki, Miho Shidahara, Masayasu Miyake, Rin Matsuda, Akie Inami & Manabu Tashiro

  7. Division of Medical Physics, Tohoku University School of Medicine, Sendai, 980-8575, Japan

    Miho Shidahara

Authors
  1. Ryuichi Harada
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  2. Nobuyuki Okamura
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  3. Shozo Furumoto
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  4. Katsutoshi Furukawa
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  5. Aiko Ishiki
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  8. Shoichi Watanuki
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  14. Takeo Yoshikawa
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  17. Ren Iwata
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  18. Manabu Tashiro
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  19. Kazuhiko Yanai
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  20. Hiroyuki Arai
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  21. Yukitsuka Kudo
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Corresponding author

Correspondence to Nobuyuki Okamura.

Electronic supplementary material

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Supplementary Table 1

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Supplementary Table 2

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Supplementary Figure 1

Correlation between MMSE scores and [18F]THK-5117 SUVR in the inferior temporal cortex of AD patients

High resolution image (EPS 1651 kb)

Supplementary Figure 2

Association between [18F]THK-5117 and [11C]PiB SUVR values in the ventrolateral prefrontal cortex, inferior temporal cortex, parietal cortex, occipital cortex, posterior cingulate cortex and hippocampus

High resolution image (EPS 778 kb)

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Harada, R., Okamura, N., Furumoto, S. et al. [18F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 42, 1052–1061 (2015). https://doi.org/10.1007/s00259-015-3035-4

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  • DOI: https://doi.org/10.1007/s00259-015-3035-4

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