title: A (68)Ga complex based on benzofuran scaffold for the detection of β-amyloid plaques.
abstract: Since the imaging of β-amyloid (Aβ) plaques in the brain is believed to be a useful tool for the early diagnosis of Alzheimer's disease (AD), a number of imaging probes to detect Aβ plaques have been developed. Because the radionuclide (68)Ga (t1/2=68 min) for PET imaging could become an attractive alternative to (11)C and (18)F, we designed and synthesized a benzofuran derivative conjugated with a (68)Ga complex ((68)Ga-DOTA-C3-BF) as a novel Aβ imaging probe. In an in vitro binding assay, Ga-DOTA-C3-BF showed high affinity for Aβ(1-42) aggregates (Ki=10.8 nM). The Ga-DOTA-C3-BF clearly stained Aβ plaques in a section of Tg2576 mouse, reflecting the affinity for Aβ(1-42) aggregates in vitro. In a biodistribution study in normal mice, (68)Ga-DOTA-C3-BF displayed low initial uptake (0.45% ID/g) in the brain at 2 min post-injection. While improvement of the brain uptake of (68)Ga complexes appears to be essential, these results suggest that novel PET imaging probes that include (68)Ga as the radionuclide for PET may be feasible.
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. Electronic address: ono@pharm.kyoto-u.ac.jp.
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: Shimpei
authors.initials: S
authors.lastname: Iikuni
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: 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: 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: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005710:Gallium Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000032:analysis*; D058225:Plaque, Amyloid / Q000175:diagnosis*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D016229:Amyloid beta-Peptides; D001572:Benzofurans; D005710:Gallium Radioisotopes; D009942:Organometallic Compounds; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; C075222:amyloid beta-protein (1-42); C105430:benzofuran
keywords: Amyloid imaging; Ga-68; PET; Probe