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In vivo detection of prion amyloid plaques using [11C]BF-227 PET

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

Abstract

Purpose

In vivo detection of pathological prion protein (PrP) in the brain is potentially useful for the diagnosis of transmissible spongiform encephalopathies (TSEs). However, there are no non-invasive ante-mortem means for detection of pathological PrP deposition in the brain. The purpose of this study is to evaluate the amyloid imaging tracer BF-227 with positron emission tomography (PET) for the non-invasive detection of PrP amyloid in the brain.

Methods

The binding ability of BF-227 to PrP amyloid was investigated using autoradiography and fluorescence microscopy. Five patients with TSEs, including three patients with Gerstmann-Sträussler-Scheinker disease (GSS) and two patients with sporadic Creutzfeldt-Jakob disease (CJD), underwent [11C]BF-227 PET scans. Results were compared with data from 10 normal controls and 17 patients with Alzheimer’s disease (AD). The regional to pons standardized uptake value ratio was calculated as an index of BF-227 retention.

Results

Binding of BF-227 to PrP plaques was confirmed using brain samples from autopsy-confirmed GSS cases. In clinical PET study, significantly higher retention of BF-227 was detected in the cerebellum, thalamus and lateral temporal cortex of GSS patients compared to that in the corresponding tissues of normal controls. GSS patients also showed higher retention of BF-227 in the cerebellum, thalamus and medial temporal cortex compared to AD patients. In contrast, the two CJD patients showed no obvious retention of BF-227 in the brain.

Conclusion

Although [11C]BF-227 is a non-specific imaging marker of cerebral amyloidosis, it is useful for in vivo detection of PrP plaques in the human brain in GSS, based on the regional distribution of the tracer. PET amyloid imaging might provide a means for both early diagnosis and non-invasive disease monitoring of certain forms of TSEs.

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Acknowledgment

We appreciate the assistance of Dr. S. Watanuki, Dr. M. Miyake and Dr. H. Takashima in the clinical PET studies. This study was supported in part by the Program for the Promotion of Fundamental Studies in Health Science of the NIBIO in Japan, Industrial Technology Research Grant Program of the NEDO in Japan, and Health and Labor Sciences Research Grants (Translational Research and Research on Measures for Intractable Diseases) from the Ministry of Health, Labor, and Welfare of Japan.

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Authors and Affiliations

  1. Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan

    Nobuyuki Okamura, Shozo Furumoto & Kazuhiko Yanai

  2. Department of Neurology, Tohoku University School of Medicine, Sendai, Japan

    Yusei Shiga & Yasuhito Itoyama

  3. Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan

    Shozo Furumoto & Ren Iwata

  4. Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan

    Manabu Tashiro

  5. Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan

    Yoshio Tsuboi

  6. Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan

    Katsutoshi Furukawa & Hiroyuki Arai

  7. Innovation of New Biomedical Engineering Center, Tohoku University, Sendai, Japan

    Yukitsuka Kudo

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

    Katsumi Doh-ura

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  1. Nobuyuki Okamura
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  2. Yusei Shiga
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  3. Shozo Furumoto
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  12. Katsumi Doh-ura
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Correspondence to Katsumi Doh-ura.

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Okamura, N., Shiga, Y., Furumoto, S. et al. In vivo detection of prion amyloid plaques using [11C]BF-227 PET. Eur J Nucl Med Mol Imaging 37, 934–941 (2010). https://doi.org/10.1007/s00259-009-1314-7

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  • DOI: https://doi.org/10.1007/s00259-009-1314-7

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