RT Journal Article
SR Electronic
T1 <sup>18</sup>F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 208
OP 214
DO 10.2967/jnumed.115.164848
VO 57
IS 2
A1 Ryuichi Harada
A1 Nobuyuki Okamura
A1 Shozo Furumoto
A1 Katsutoshi Furukawa
A1 Aiko Ishiki
A1 Naoki Tomita
A1 Tetsuro Tago
A1 Kotaro Hiraoka
A1 Shoichi Watanuki
A1 Miho Shidahara
A1 Masayasu Miyake
A1 Yoichi Ishikawa
A1 Rin Matsuda
A1 Akie Inami
A1 Takeo Yoshikawa
A1 Yoshihito Funaki
A1 Ren Iwata
A1 Manabu Tashiro
A1 Kazuhiko Yanai
A1 Hiroyuki Arai
A1 Yukitsuka Kudo
YR 2016
UL http://jnm.snmjournals.org/content/57/2/208.abstract
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, 18F-THK5351, 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: 18F-THK5351 demonstrated higher binding affinity for hippocampal homogenates from AD brains and faster dissociation from white-matter 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-to-background 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.