A 18F-labeled BF-227 derivative as a potential radioligand for imaging dense amyloid plaques by positron emission tomography.
OBJECTIVE
The aims of this study were to evaluate the binding and pharmacokinetics of novel 18F-labeled ethenyl-benzoxazole derivatives (i.e., [18F] fluorinated amyloid imaging compound of Tohoku university ([18F]FACT)) as amyloid positron emission tomography (PET) tracers and to assess [18F]FACT efficacy in imaging of Alzheimer's disease (AD).


METHODS
Binding assay was conducted using synthetic amyloid-β (Aβ) fibrils, fluorescence microscopy, and autoradiogram in three postmortem AD brains. Pharmacokinetics of [18F]FACT was assessed using 12 Crj:CD-1 (ICR) mice. In vivo binding ability with brain amyloid was investigated using amyloid precursor protein (APP) transgenic mouse. Clinical PET scanning using [18F]FACT was performed in ten healthy controls and ten mild cognitive impairment and ten AD patients.


RESULTS
[18F]FACT showed high binding affinity for synthetic Aβ fibrils, preferential binding to dense cored plaques in brain sections, and excellent brain uptake and rapid clearance in mice. Injection in APP mice resulted in specific in vivo labeling of amyloid deposits in the brain. PET scans of AD patients showed significantly higher [18F]FACT uptake in the neocortex compared to controls (P<0.05, Kruskal-Wallis test).


CONCLUSIONS
[18F]FACT is a promising agent for imaging dense Aβ plaques in AD.
Department of Pharmacology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
Shozo
S
Furumoto
Nobuyuki
N
Okamura
Katsutoshi
K
Furukawa
Manabu
M
Tashiro
Yoichi
Y
Ishikawa
Kentaro
K
Sugi
Naoki
N
Tomita
Masaaki
M
Waragai
Ryuichi
R
Harada
Tetsuro
T
Tago
Ren
R
Iwata
Kazuhiko
K
Yanai
Hiroyuki
H
Arai
Yukitsuka
Y
Kudo
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D003710:Demography; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution
C516779:2-(2-(2-dimethylaminothiazol-5-yl)ethenyl)-6-(2-(fluoro)ethoxy)benzoxazole; D016229:Amyloid beta-Peptides; D001583:Benzoxazoles; D005462:Fluorine Radioisotopes; D008024:Ligands; D013844:Thiazoles