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