TY - JOUR
T1 - 18F-THK5351
T2 - A novel PET radiotracer for imaging neurofibrillary pathology in Alzheimer disease
AU - Harada, Ryuichi
AU - Okamura, Nobuyuki
AU - Furumoto, Shozo
AU - Furukawa, Katsutoshi
AU - Ishiki, Aiko
AU - Tomita, Naoki
AU - Tago, Tetsuro
AU - Hiraoka, Kotaro
AU - Watanuki, Shoichi
AU - Shidahara, Miho
AU - Miyake, Masayasu
AU - Ishikawa, Yoichi
AU - Matsuda, Rin
AU - Inami, Akie
AU - Yoshikawa, Takeo
AU - Funaki, Yoshihito
AU - Iwata, Ren
AU - Tashiro, Manabu
AU - Yanai, Kazuhiko
AU - Arai, Hiroyuki
AU - Kudo, Yukitsuka
N1 - Publisher Copyright:
© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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, 18FTHK5351, through compound optimization of arylquinoline derivatives. Methods: The in vitro binDing properties, pharmacokinetics, and safety of 18F-THK5351 were investigated, and a clinical study on Alzheimer disease (AD) patients was performed. Results: 18FTHK5351 demonstrated higher binDing affinity for hippocampal homogenates from AD brains and faster dissociation from whitematter tissue than did 18F-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-tobackground ratio than did THK5117. THK5351 exhibited favorable pharmacokinetics and no defluorination in mice. In first-in-human PET studies in AD patients, 18F-THK5351 demonstrated faster kinetics, higher contrast, and lower retention in subcortical white matter than18F-THK5117. Conclusion: 18F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.
AB - 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, 18FTHK5351, through compound optimization of arylquinoline derivatives. Methods: The in vitro binDing properties, pharmacokinetics, and safety of 18F-THK5351 were investigated, and a clinical study on Alzheimer disease (AD) patients was performed. Results: 18FTHK5351 demonstrated higher binDing affinity for hippocampal homogenates from AD brains and faster dissociation from whitematter tissue than did 18F-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-tobackground ratio than did THK5117. THK5351 exhibited favorable pharmacokinetics and no defluorination in mice. In first-in-human PET studies in AD patients, 18F-THK5351 demonstrated faster kinetics, higher contrast, and lower retention in subcortical white matter than18F-THK5117. Conclusion: 18F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.
KW - Alzheimer's disease
KW - F-THK5351
KW - PET
KW - Radiotracer
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=84958640060&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84958640060&partnerID=8YFLogxK
U2 - 10.2967/jnumed.115.164848
DO - 10.2967/jnumed.115.164848
M3 - Article
C2 - 26541774
AN - SCOPUS:84958640060
SN - 0161-5505
VL - 57
SP - 208
EP - 214
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 2
ER -
