title: (18)F-labeled phenyldiazenyl benzothiazole for in vivo imaging of neurofibrillary tangles in Alzheimer's disease brains.
abstract: We synthesized and evaluated (E)-4-((6-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)benzo[d]thiazol-2-yl)diazenyl)-N,N-dimethylaniline (FPPDB) as a probe for the imaging of neurofibrillary tangles (NFTs) in patients with Alzheimer's disease (AD). In assays using thioflavin S (ThS) as a competitive ligand, FPPDB competed with ThS well and showed high affinity for both tau and Aβ1-42 aggregates (K i = 13.0 and 20.0 nM, respectively). The results of saturation binding assays also verified that FPPDB bound to both tau and Aβ1-42 aggregates with high affinity (K d = 44.8 nM and B max = 45.8 pmol/nmol protein for tau aggregates and K d = 45.4 nM and B max = 38.9 pmol/nmol protein for Aβ1-42 aggregates). Furthermore, [(18)F]FPPDB substantially labeled NFTs and senile plaques in AD brain sections but not control brain sections. In biodistribution experiments using normal mice, [(18)F]FPPDB displayed higher uptake (4.28% ID/g at 2 min postinjection) into and washout (2.53% ID/g at 60 min postinjection) from the brain with time. On the basis of the chemical structure of FPPDB, further increases in selective binding to tau aggregates may lead to the development of more useful probes for the imaging of NFTs in AD brains.
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumura
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University , 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamoto
authors.affiliation: Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University , 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Togashi
authors.affiliation: Department of Neurology, Graduate School of Medicine, Kyoto University , 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Neurology, Graduate School of Medicine, Kyoto University , 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
authors.affiliation: Department of Neurology, Graduate School of Medicine, Kyoto University , 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
keywords: Alzheimer's disease (AD); PET; benzothiazole; imaging; neurofibrillary tangles (NFTs)