Rhenium and technetium complexes that bind to amyloid-beta plaques

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-beta peptide. Technetium-99m complexes that bind to amyloid-beta plaques could provide important diagnostic information on amyloid-beta 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 Tc-99m) core. The rhenium carbonyl complexes with tridentate co-ligands that included a stilbene functional group and a dimethylamino substituent bound to amyloid-beta present in human frontal cortex brain tissue from subjects with Alzheimer's disease. This chemistry was extended to make the analogous [Tc-99m(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).