title: Structure-Activity Relationships and in Vivo Evaluation of Quinoxaline Derivatives for PET Imaging of β-Amyloid Plaques.
abstract: This letter describes the synthesis, structure-activity relationships, and in vivo evaluation of a new series of 2-phenylquinoxaline (PQ) derivatives for imaging β-amyloid (Aβ) plaques in Alzheimer's disease (AD). In experiments in vitro, the affinity of the derivatives for Aβ aggregates varied, with K i values of 0.895 to 1180 nM. In brain sections from AD patients, derivatives with a K i of less than 111 nM intensely labeled Aβ plaques, while those with values over 242 nM showed no marked labeling. In biodistribution experiments using normal mice, the derivatives showed good uptake into (4.69-7.59 %ID/g at 2 or 10 min postinjection) and subsequent washout from (1.48-3.08 %ID/g at 60 min postinjection) the brain. In addition, [(18)F]PQ-6 labeled Aβ plaques in vivo in APP transgenic mice, while it showed nonspecific binding in the white matter. Further structural optimization based on [(18)F]PQ-6 may lead to more useful PET probes for imaging Aβ plaques.
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: Yoshimura
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: 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: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
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: Mengchao
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University , 54 Shogoin Kawahara-cho, 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 Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Togashi
authors.affiliation: Department of Neuroscience, Graduate School of Medicine, Kyoto University , 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Neuroscience, Graduate School of Medicine, Kyoto University , 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
authors.affiliation: Department of Neuroscience, Graduate School of Medicine, Kyoto University , 54 Shogoin Kawahara-cho, 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; quinoxaline; structure−activity relationships; β-amyloid (Aβ)