title: 18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease.
abstract: Imaging of neurofibrillary pathology in the brain helps in diagnosing dementia, tracking disease progression, and evaluating the therapeutic efficacy of antidementia drugs. The radiotracers used in this imaging must be highly sensitive and specific for tau protein fibrils in the human brain. We developed a novel tau PET tracer, (18)F-THK5351, through compound optimization of arylquinoline derivatives.
  
  
  METHODS
  The in vitro binding properties, pharmacokinetics, and safety of (18)F-THK5351 were investigated, and a clinical study on Alzheimer disease (AD) patients was performed.
  
  
  RESULTS
  (18)F-THK5351 demonstrated higher binding affinity for hippocampal homogenates from AD brains and faster dissociation from white-matter tissue than did (18)F-THK5117. The THK5351 binding amount correlated with the amount of tau deposits in human brain samples. Autoradiography of brain sections revealed that THK5351 bound to neurofibrillary tangles selectively and with a higher signal-to-background ratio than did THK5117. THK5351 exhibited favorable pharmacokinetics and no defluorination in mice. In first-in-human PET studies in AD patients, (18)F-THK5351 demonstrated faster kinetics, higher contrast, and lower retention in subcortical white matter than(18)F-THK5117.
  
  
  CONCLUSIONS
  (18)F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.
authors.affiliation: Division of Neuro-imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Harada
authors.affiliation: Division of Neuro-imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan nookamura@med.tohoku.ac.jp.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Furumoto
authors.affiliation: Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; and.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; and.
authors.forename: Aiko
authors.initials: A
authors.lastname: Ishiki
authors.affiliation: Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; and.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tomita
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Tago
authors.affiliation: Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hiraoka
authors.affiliation: Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Watanuki
authors.affiliation: Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan Division of Medical Physics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Shidahara
authors.affiliation: Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Miyake
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Rin
authors.initials: R
authors.lastname: Matsuda
authors.affiliation: Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Akie
authors.initials: A
authors.lastname: Inami
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Funaki
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Ren
authors.initials: R
authors.lastname: Iwata
authors.affiliation: Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Tashiro
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
authors.affiliation: Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; and.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.affiliation: Division of Neuro-imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Yukitsuka
authors.initials: Y
authors.lastname: Kudo
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D000631:Aminopyridines / Q000009:adverse effects / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D008813:Mice, Inbred ICR; D016874:Neurofibrillary Tangles / Q000000981:diagnostic imaging* / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D011804:Quinolines / Q000009:adverse effects / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000138:chemical synthesis / Q000493:pharmacokinetics; D014018:Tissue Distribution; D066127:White Matter / Q000000981:diagnostic imaging / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000631:Aminopyridines; D011804:Quinolines; D019275:Radiopharmaceuticals; C000608225:THK5351; D016875:tau Proteins
keywords: 18F-THK5351; Alzheimer’s disease; PET; radiotracer; tau