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18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease.
Harada, Ryuichi; Okamura, Nobuyuki; Furumoto, Shozo; Furukawa, Katsutoshi; Ishiki, Aiko; Tomita, Naoki; Tago, Tetsuro; Hiraoka, Kotaro; Watanuki, Shoichi; Shidahara, Miho; Miyake, Masayasu; Ishikawa, Yoichi; Matsuda, Rin; Inami, Akie; Yoshikawa, Takeo; Funaki, Yoshihito; Iwata, Ren; Tashiro, Manabu; Yanai, Kazuhiko; Arai, Hiroyuki; Kudo, Yukitsuka.
Afiliación
  • Harada R; Division of Neuro-imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
  • Okamura N; 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 nookamur
  • Furumoto S; Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
  • Furukawa K; Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; and.
  • Ishiki A; Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; and.
  • Tomita N; Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; and.
  • Tago T; Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
  • Hiraoka K; Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
  • Watanuki S; Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
  • Shidahara M; Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan Division of Medical Physics, Tohoku University School of Medicine, Sendai, Japan.
  • Miyake M; Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
  • Ishikawa Y; Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
  • Matsuda R; Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
  • Inami A; Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
  • Yoshikawa T; Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
  • Funaki Y; Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
  • Iwata R; Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
  • Tashiro M; Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
  • Yanai K; Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
  • Arai H; Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; and.
  • Kudo Y; 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.
J Nucl Med ; 57(2): 208-14, 2016 Feb.
Article en En | MEDLINE | ID: mdl-26541774
ABSTRACT
UNLABELLED 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.

CONCLUSION:

(18)F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ovillos Neurofibrilares / Radiofármacos / Tomografía de Emisión de Positrones / Enfermedad de Alzheimer Tipo de estudio: Screening_studies Límite: Animals Idioma: En Revista: J Nucl Med Año: 2016 Tipo del documento: Article País de afiliación: Japón
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ovillos Neurofibrilares / Radiofármacos / Tomografía de Emisión de Positrones / Enfermedad de Alzheimer Tipo de estudio: Screening_studies Límite: Animals Idioma: En Revista: J Nucl Med Año: 2016 Tipo del documento: Article País de afiliación: Japón