title: Rhenium and technetium complexes that bind to amyloid-β plaques.
abstract: Alzheimer's disease is associated with the presence of insoluble protein deposits in the brain called amyloid plaques. The major constituent of these deposits is aggregated amyloid-β peptide. Technetium-99m complexes that bind to amyloid-β plaques could provide important diagnostic information on amyloid-β plaque burden using Single Photon Emission Computed Tomography (SPECT). Tridentate ligands with a stilbene functional group were used to form complexes with the fac-[M(I)(CO)3](+) (M = Re or (99m)Tc) core. The rhenium carbonyl complexes with tridentate co-ligands that included a stilbene functional group and a dimethylamino substituent bound to amyloid-β present in human frontal cortex brain tissue from subjects with Alzheimer's disease. This chemistry was extended to make the analogous [(99m)Tc(I)(CO)3](+) complexes and the complexes were sufficiently stable in human serum. Whilst the lipophilicity (log D7.4) of the technetium complexes appeared ideally suited for penetration of the blood-brain barrier, preliminary biodistribution studies in an AD mouse model (APP/PS1) revealed relatively low brain uptake (0.24% ID g(-1) at 2 min post injection).
authors.affiliation: School of Chemistry, University of Melbourne, Melbourne, 3010, Australia. pauld@unimelb.edu.au.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hayne
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: North
authors.forename: Michelle
authors.initials: M
authors.lastname: Fodero-Tavoletti
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: White
authors.forename: Lin W
authors.initials: LW
authors.lastname: Hung
authors.forename: Angela
authors.initials: A
authors.lastname: Rigopoulos
authors.forename: Catriona A
authors.initials: CA
authors.lastname: McLean
authors.forename: Paul A
authors.initials: PA
authors.lastname: Adlard
authors.forename: Uwe
authors.initials: U
authors.lastname: Ackermann
authors.forename: Henri
authors.initials: H
authors.lastname: Tochon-Danguy
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Barnham
authors.forename: Paul S
authors.initials: PS
authors.lastname: Donnelly
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D004355:Drug Stability; D006801:Humans; D051379:Mice; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000378:metabolism; D011485:Protein Binding; D012211:Rhenium / Q000737:chemistry*; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D016229:Amyloid beta-Peptides; D009942:Organometallic Compounds; D012211:Rhenium; D013667:Technetium