title: PiB-Conjugated, Metal-Based Imaging Probes: Multimodal Approaches for the Visualization of β-Amyloid Plaques.
abstract: In an effort toward the visualization of β-amyloid plaques by in vivo imaging techniques, we have conjugated an optimized derivative of the Pittsburgh compound B (PiB), a well-established marker of Aβ plaques, to DO3A-monoamide that is capable of forming stable, noncharged complexes with different trivalent metal ions including Gd(3+) for MRI and (111)In(3+) for SPECT applications. Proton relaxivity measurements evidenced binding of Gd(DO3A-PiB) to the amyloid peptide Aβ1-40 and to human serum albumin, resulting in a two- and four-fold relaxivity increase, respectively. Ex vivo immunohistochemical studies showed that the DO3A-PiB complexes selectively target Aβ plaques on Alzheimer's disease human brain tissue. Ex vivo biodistribution data obtained for the (111)In-analogue pointed to a moderate blood-brain barrier (BBB) penetration in adult male Swiss mice (without amyloid deposits) with 0.36% ID/g in the cortex at 2 min postinjection.
authors.affiliation: Centre de Biophysique Moléculaire, CNRS , Rue Charles Sadron, 45071 Orléans Cedex 2, France ; Department of Life Sciences, Center of Neurosciences and Cell Biology (CNC), and Coimbra Chemistry Center, University of Coimbra , Portugal.
authors.forename: André F
authors.initials: AF
authors.lastname: Martins
authors.affiliation: Centre de Biophysique Moléculaire, CNRS , Rue Charles Sadron, 45071 Orléans Cedex 2, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Morfin
authors.affiliation: Centre de Biophysique Moléculaire, CNRS , Rue Charles Sadron, 45071 Orléans Cedex 2, France ; Department of Analytical Chemistry, Charles University in Prague , Albertov 2030, 12840 Prague, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Kubíčková
authors.affiliation: Centre de Biophysique Moléculaire, CNRS , Rue Charles Sadron, 45071 Orléans Cedex 2, France.
authors.forename: Vojtěch
authors.initials: V
authors.lastname: Kubíček
authors.affiliation: Institut de Chimie Organique et Analytique, UMR 7311 CNRS/Université d'Orléans , rue de Chartres, 45067 Orléans, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Buron
authors.affiliation: Institut de Chimie Organique et Analytique, UMR 7311 CNRS/Université d'Orléans , rue de Chartres, 45067 Orléans, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Suzenet
authors.affiliation: Laboratoire CSPBAT, CNRS UMR 7244, UFR-SMBH, Université Paris 13 , 74 rue Marcel Cachin, 93017 Bobigny, France.
authors.forename: Milena
authors.initials: M
authors.lastname: Salerno
authors.affiliation: Centre de Recherche de l'Institut du Cerveau et de la Moelle, CNRS UMR7225, INSERM, UMR975 and UPMC, Hôpital de la Pitié-Salpêtrière 47 , Bd de l'Hôpital 75013 Paris, France.
authors.forename: Adina N
authors.initials: AN
authors.lastname: Lazar
authors.affiliation: Centre de Recherche de l'Institut du Cerveau et de la Moelle, CNRS UMR7225, INSERM, UMR975 and UPMC, Hôpital de la Pitié-Salpêtrière 47 , Bd de l'Hôpital 75013 Paris, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.affiliation: Inserm, U930, Université François Rabelais de Tours , CHRU de Tours, 37044 Tours Cedex 9, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Arlicot
authors.affiliation: Inserm, U930, Université François Rabelais de Tours , CHRU de Tours, 37044 Tours Cedex 9, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Guilloteau
authors.affiliation: Department of Life Sciences, Center of Neurosciences and Cell Biology (CNC), and Coimbra Chemistry Center, University of Coimbra , Portugal.
authors.forename: Carlos F G C
authors.initials: CF
authors.lastname: Geraldes
authors.affiliation: Centre de Biophysique Moléculaire, CNRS , Rue Charles Sadron, 45071 Orléans Cedex 2, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Tóth
keywords: 111In3+; Alzheimer’s disease; Gd3+; Pittsburgh compound B; amyloid plaques; imaging agents