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Comparison of the binding characteristics of [18F]THK-523 and other amyloid imaging tracers to Alzheimer’s disease pathology

  • Ryuichi Harada
  • Nobuyuki Okamura
  • Shozo Furumoto
  • Tetsuro Tago
  • Masahiro Maruyama
  • Makoto Higuchi
  • Takeo Yoshikawa
  • Hiroyuki Arai
  • Ren Iwata
  • Yukitsuka Kudo
  • Kazuhiko Yanai
Original Article

Abstract

Purpose

Extensive deposition of senile plaques and neurofibrillary tangles in the brain is a pathological hallmark of Alzheimer’s disease (AD). Although several PET imaging agents have been developed for in vivo detection of senile plaques, no PET probe is currently available for selective detection of neurofibrillary tangles in the living human brain. Recently, [18F]THK-523 was developed as a potential in vivo imaging probe for tau pathology. The purpose of this study was to compare the binding properties of [18F]THK-523 and other amyloid imaging agents, including PiB, BF-227 and FDDNP, to synthetic protein fibrils and human brain tissue.

Methods

In vitro radioligand binding assays were conducted using synthetic amyloid β42 and K18ΔK280-tau fibrils. Nonspecific binding was determined by the addition of unlabelled compounds at a concentration of 2 μM. To examine radioligand binding to neuropathological lesions, in vitro autoradiography was conducted using sections of AD brain.

Results

[18F]THK-523 showed higher affinity for tau fibrils than for Aβ fibrils, whereas the other probes showed a higher affinity for Aβ fibrils. The autoradiographic analysis indicated that [18F]THK-523 accumulated in the regions containing a high density of tau protein deposits. Conversely, PiB and BF-227 accumulated in the regions containing a high density of Aβ plaques.

Conclusion

These findings suggest that the unique binding profile of [18F]THK-523 can be used to identify tau deposits in AD brain.

Keywords

PET probes Tau Amyloid Alzheimer’s disease 

Notes

Acknowledgments

This study was supported by the Industrial Technology Research Grant Program of the NEDO in Japan, Health and Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare of Japan, and Grant-in-Aid for Scientific Research (B) (23390297).

Supplementary material

259_2012_2261_MOESM2_ESM.pdf (143 kb)
ESM 1 Supplementary figure. HPLC profiles of [11C]PiB, [18F]FDDNP, [11C]BF-227, [18F]BF-227, and [18F]THK-523. HPLC conditions: Column: Intersil ODS-4 (5 μm, 4.6 × 150 mm), CH3CN/NaH2PO4 (20 mM) = 50/50, UV at 254 nm for PiB, 65/35, at 254 nm for FDDNP, 55/45 at 400 nm for BF-227, and 50/50, at 360 nm for THK-523, 2.0 mL/min for [11C]BF-227, 1.5 mL/min for the others. The UV peaks within around 2 min were DMSO and ascorvic acid because the solutions contain DMSO as a solvent and ascorvic acid to prevent radioactive decomposition. The slight difference in retention time between the radioactive peak and the UV peak is due to the configuration of the detector system (PDF 142 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Ryuichi Harada
    • 1
  • Nobuyuki Okamura
    • 1
  • Shozo Furumoto
    • 1
    • 2
  • Tetsuro Tago
    • 2
  • Masahiro Maruyama
    • 3
  • Makoto Higuchi
    • 3
  • Takeo Yoshikawa
    • 1
  • Hiroyuki Arai
    • 4
  • Ren Iwata
    • 2
  • Yukitsuka Kudo
    • 5
  • Kazuhiko Yanai
    • 1
  1. 1.Department of PharmacologyTohoku University School of MedicineSendaiJapan
  2. 2.Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope CenterTohoku UniversitySendaiJapan
  3. 3.Molecular Imaging Center, National Institute of Radiological SciencesChibaJapan
  4. 4.Department of Geriatrics and Gerontology, Institute of Development, Aging and CancerTohoku UniversitySendaiJapan
  5. 5.Innovation of New Biomedical Engineering CenterTohoku UniversitySendaiJapan

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