Rhenium and technetium complexes that bind to amyloid-β plaques

David J. Hayne; Andrea J. North; Michelle Fodero-Tavoletti; Jonathan M. White; Lin W. Hung; Angela Rigopoulos; Catriona A. McLean; Paul A. Adlard; Uwe Ackermann; Henri Tochon-Danguy; Victor L. Villemagne; Kevin J. Barnham; Paul S. Donnelly

doi:10.1039/C4DT02969K

Rhenium and technetium complexes that bind to amyloid-β plaques†

David J. Hayne,^ab Andrea J. North,^ab Michelle Fodero-Tavoletti,^ce Jonathan M. White,^ab Lin W. Hung,^bc Angela Rigopoulos,^d Catriona A. McLean,^cf Paul A. Adlard,^c Uwe Ackermann,^e Henri Tochon-Danguy,^e Victor L. Villemagne,^ce Kevin J. Barnham^bcg and Paul S. Donnelly*^ab

Author affiliations

* Corresponding authors

^a School of Chemistry, University of Melbourne, Melbourne, Australia
E-mail: pauld@unimelb.edu.au

^b Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Road, Victoria 3010, Australia

^c Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Melbourne, Victoria, Australia

^d Ludwig Institute for Cancer Research, Heidelberg, Victoria, Australia

^e Department of Molecular Imaging and Therapy, Austin Health, Melbourne, Heidelberg, Victoria 3084, Australia

^f Department of Anatomical Pathology, The Alfred Hospital, Victoria 3181, Australia

^g Department of Pharmacology, University of Melbourne, Parkville, Melbourne, Heidelberg, Victoria 3084, Australia

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 ^99mTc) 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 [^99mTc^I(CO)₃]⁺ complexes and the complexes were sufficiently stable in human serum. Whilst the lipophilicity (log D_7.4) 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).

This article is part of the themed collection: Dalton Discussion 15: Metal ions in medical imaging

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Rhenium and technetium complexes that bind to amyloid-β plaques†

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Rhenium and technetium complexes that bind to amyloid-β plaques

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