title: Development of dual functional SPECT/fluorescent probes for imaging cerebral beta-amyloid plaques.
abstract: The imaging of beta-amyloid (Abeta) aggregates in the brain may lead to the early detection of Alzheimer's disease (AD) and monitoring of the progression and effectiveness of treatment. The purpose of this study was to develop dual modality SPECT and fluorescent probes based on boron dipyrromethane (BODIPY) as a core structure. We designed and synthesized an (125)I-labeled derivative of BODIPY (BODIPY7). BODIPY7 had a K(i) value of 108nM for Abeta(1-42) aggregates and exhibited peaks of absorption/emission at 606/613nm. It detected Abeta plaques in sections of brain tissue from an animal model of AD and displayed low uptake in the brain and high uptake in the liver in normal mice. Although additional modifications of the BODIPY scaffold are necessary to improve brain uptake, these results should aid the development of dual functional SPECT/fluorescent probes for the imaging of Abeta plaques in the brain.
authors.affiliation: Kyoto University, Sakyo-ku, Japan. ono@pharm.kyoto-u.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Manami
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kimura
authors.forename: Shun
authors.initials: S
authors.lastname: Hayashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Kawashima
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D015394:Molecular Structure; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D016229:Amyloid beta-Peptides; D001896:Boron Compounds; D005456:Fluorescent Dyes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)