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18F-THK5351 positron emission tomography imaging for Gerstmann-Sträussler-Scheinker disease

  • Yuka Hama
    Affiliations
    Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8551, Japan
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  • Author Footnotes
    1 Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2–6-1 Musashidai, Fuchu, Tokyo, 183–0042, Japan
    Yuji Saitoh
    Correspondence
    Corresponding author at: Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8551, Japan.
    Footnotes
    1 Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2–6-1 Musashidai, Fuchu, Tokyo, 183–0042, Japan
    Affiliations
    Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8551, Japan

    Research Center for Neurocognitive Disorders, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8551, Japan
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  • Etsuko Imabayashi
    Affiliations
    Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8551, Japan

    Department of Molecular Imaging and Theranostics, Quantum Life and Medical Science Directorate, National Institute for Quantum Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
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  • Yuko Morimoto
    Affiliations
    Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8551, Japan
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  • Tadashi Tsukamoto
    Affiliations
    Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8551, Japan

    Research Center for Neurocognitive Disorders, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8551, Japan
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  • Katsuya Sato
    Affiliations
    Department of Locomotive Rehabilitation Science, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8102, Japan
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  • Tetsuyuki Kitamoto
    Affiliations
    Department of Neurological Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
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  • Hidehiro Mizusawa
    Affiliations
    Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8551, Japan
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  • Author Footnotes
    2 Department of Biofunctional Imaging, Fukushima Medical University, 2–2-1 Otemachi, Chiyoda-ku, Tokyo, 100–0004, Japan
    Hiroshi Matsuda
    Footnotes
    2 Department of Biofunctional Imaging, Fukushima Medical University, 2–2-1 Otemachi, Chiyoda-ku, Tokyo, 100–0004, Japan
    Affiliations
    Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8551, Japan
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  • Yuji Takahashi
    Affiliations
    Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8551, Japan
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  • Author Footnotes
    1 Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2–6-1 Musashidai, Fuchu, Tokyo, 183–0042, Japan
    2 Department of Biofunctional Imaging, Fukushima Medical University, 2–2-1 Otemachi, Chiyoda-ku, Tokyo, 100–0004, Japan
Published:August 03, 2022DOI:https://doi.org/10.1016/j.jns.2022.120379
      Gerstmann-Sträussler-Scheinker disease (GSS) is an autosomal dominant prion disease caused by a mutation in the prion protein gene (PRNP). The Pro→Leu mutation at codon 102 of PRNP (P102L) is the most common mutation associated with GSS (GSS-P102L), and patients commonly develop progressive cerebellar ataxia and dementia [
      • Ghetti B.
      • Piccardo P.
      • Zanusso G.
      Dominantly inherited prion protein cerebral amyloidoses - a modern view of Gerstmann-Sträussler-Scheinker.
      ]. GSS is pathologically characterized by amyloid plaques consisting of prion protein (PrP) that are primarily observed in the cerebellum and cerebral cortex, astrocytosis, and spongiform degeneration [
      • Ghetti B.
      • Piccardo P.
      • Zanusso G.
      Dominantly inherited prion protein cerebral amyloidoses - a modern view of Gerstmann-Sträussler-Scheinker.
      ,
      • Bugiani O.
      • Giaccone G.
      • Piccardo P.
      • Morbin M.
      • Tagliavini F.
      • Ghetti B.
      Neuropathology of Gerstmann-Straussler-Scheinker disease.
      ]. Although the 18F-THK5351 tracer for positron emission tomography (PET) was originally developed to bind to abnormally deposited tau protein [
      • Harada R.
      • Okamura N.
      • Furumoto S.
      • Furukawa K.
      • Ishiki A.
      • Tomita N.
      • Tago T.
      • Hiraoka K.
      • Watanuki S.
      • Shidahara M.
      • Miyake M.
      • Ishikawa Y.
      • Matsuda R.
      • Inami A.
      • Yoshikawa T.
      • Funaki Y.
      • Iwata R.
      • Tashiro M.
      • Yanai K.
      • Arai H.
      • Kudo Y.
      18F-THK5351: a novel PET radiotracer for imaging neurofibrillary pathology in Alzheimer disease.
      ], recent evidence indicates that it exhibits off-target binding to monoamine oxidase-B (MAO-B) expressed in astrocytes [
      • Ng K.P.
      • Pascoal T.A.
      • Mathotaarachchi S.
      • Therriault J.
      • Kang M.S.
      • Shin M.
      • Guiot M.C.
      • Guo Q.
      • Harada R.
      • Comley R.A.
      • Massarweh G.
      • Soucy J.P.
      • Okamura N.
      • Gauthier S.
      • Rosa-Neto P.
      Monoamine oxidase B inhibitor, selegiline, reduces (18)F-THK5351 uptake in the human brain.
      ,
      • Ishiki A.
      • Harada R.
      • Kai H.
      • Sato N.
      • Totsune T.
      • Tomita N.
      • Watanuki S.
      • Hiraoka K.
      • Ishikawa Y.
      • Funaki Y.
      • Iwata R.
      • Furumoto S.
      • Tashiro M.
      • Sasano H.
      • Kitamoto T.
      • Kudo Y.
      • Yanai K.
      • Furukawa K.
      • Okamura N.
      • Arai H.
      Neuroimaging-pathological correlations of [(18)F]THK5351 PET in progressive supranuclear palsy.
      ]. However, this off-target binding of the 18F-THK5351 tracer to MAO-B-expressing astrocytes can be used to visualize astrogliosis, reflecting neurodegenerative processes other than tauopathy in various neurodegenerative disorders [
      • Kim H.J.
      • Cho H.
      • Park S.
      • Jang H.
      • Ryu Y.H.
      • Choi J.Y.
      • Moon S.H.
      • Oh S.J.
      • Oh M.
      • Na D.L.
      • Lyoo C.H.
      • Kim E.J.
      • Seeley W.W.
      • Kim J.S.
      • Choi K.C.
      • Seo S.W.
      THK5351 and flortaucipir PET with pathological correlation in a Creutzfeldt-Jakob disease patient: a case report.
      ,
      • Saitoh Y.
      • Imabayashi E.
      • Mukai T.
      • Matsuda H.
      • Takahashi Y.
      Visualization of motor cortex involvement by 18F-THK5351 PET potentially strengthens diagnosis of amyotrophic lateral sclerosis.
      ]. Here, we report a patient with genetically confirmed GSS harboring the P102L mutation who was examined by 18F-THK5351 PET.

      Keywords

      Abbreviations:

      18F-FDG (18F-2-fluorodeoxy-d-glucose), 99mTc-ECD (99mTc-ethyl cysteinate dimer), DWI (diffusion-weighted imaging), GSS (Gerstmann-Sträussler-Scheinker disease), MAO-B (monoamine oxidase-B), P102L (Pro→Leu mutation at codon 102 of prion protein gene), PET (positron emission tomography), PRNP (prion protein gene), PrP (prion protein), SPECT (single-photon emission computed tomography.), SUV (standardized uptake value), SUVR (standardized uptake value ratio), T1WI (T1-weighted imaging)
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