title: Technetium-99m labeled pyridyl benzofuran derivatives as single photon emission computed tomography imaging probes for β-amyloid plaques in Alzheimer's brains.
abstract: Three novel (99m)Tc-labeled pyridyl benzofuran derivatives were tested as potential probes for imaging β-amyloid plaques using single photon emission computed tomography (SPECT). The (99m)Tc and corresponding rhenium complexes were synthesized with bis(aminoethanethiol) (BAT) as a chelating ligand. All Re complexes showed affinity for Aβ(1-42) aggregates (K(i) = 13.6-149.6 nM). Biodistribution experiments in normal mice revealed that the (99m)Tc-labeled derivatives displayed sufficient uptake in the brain (1.41-1.80% ID/g at 2 min postinjection). Notably, [(99m)Tc]BAT-Bp-2 showed a good initial uptake (1.80% ID/g at 2 min) and a reasonable washout from the brain (0.79% ID/g at 60 min). Ex vivo autoradiography with [(99m)Tc]BAT-Bp-2 revealed substantial labeling of β-amyloid plaques in sections of brain tissue from Tg2576 transgenic mice but not in the age-matched controls. [(99m)Tc]BAT-Bp-2 may be a potential SPECT probe for imaging β-amyloid plaques in Alzheimer's brains.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kimura
authors.forename: Masashi
authors.initials: M
authors.lastname: Ueda
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D012211:Rhenium; D013329:Structure-Activity Relationship; D013667:Technetium; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D016229:Amyloid beta-Peptides; D001572:Benzofurans; D002614:Chelating Agents; D056831:Coordination Complexes; D011725:Pyridines; D019275:Radiopharmaceuticals; D012211:Rhenium; D013667:Technetium