2. Academic Validation
  3. 18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease

18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease

  • J Nucl Med. 2016 Feb;57(2):208-14. doi: 10.2967/jnumed.115.164848.
Ryuichi Harada 1,  Nobuyuki Okamura 2,  Shozo Furumoto 3,  Katsutoshi Furukawa 4,  Aiko Ishiki 4,  Naoki Tomita 4,  Tetsuro Tago 3,  Kotaro Hiraoka 5,  Shoichi Watanuki 5,  Miho Shidahara 6,  Masayasu Miyake 5,  Yoichi Ishikawa 3,  Rin Matsuda 5,  Akie Inami 5,  Takeo Yoshikawa 7,  Yoshihito Funaki 3,  Ren Iwata 3,  Manabu Tashiro 5,  Kazuhiko Yanai 7,  Hiroyuki Arai 4,  Yukitsuka Kudo 8
Affiliations

Affiliations

  • 1 Division of Neuro-imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
  • 2 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.
  • 3 Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
  • 4 Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; and.
  • 5 Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
  • 6 Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan Division of Medical Physics, Tohoku University School of Medicine, Sendai, Japan.
  • 7 Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
  • 8 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.
PMID: 26541774 DOI: 10.2967/jnumed.115.164848
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.

Conclusion: (18)F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.

Keywords

18F-THK5351; Alzheimer’s disease; PET; radiotracer; tau.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z