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Rhenium and technetium complexes that bind to amyloid-β plaques

Version 2 2024-06-04, 08:06
Version 1 2017-08-04, 10:50
journal contribution
posted on 2024-06-04, 08:06 authored by David HayneDavid Hayne, AJ North, M Fodero-Tavoletti, JM White, LW Hung, A Rigopoulos, CA McLean, PA Adlard, U Ackermann, H Tochon-Danguy, VL Villemagne, KJ Barnham, PS Donnelly
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).

History

Journal

Dalton transactions

Volume

44

Pagination

4933-4944

Location

London, Eng.

eISSN

1477-9234

Language

eng

Publication classification

C Journal article, C1.1 Refereed article in a scholarly journal

Copyright notice

2015, Royal Society of Chemistry

Issue

11

Publisher

Royal Society of Chemistry