Diagnostic Imaging Agents for Alzheimer’s Disease: Copper Radiopharmaceuticals that Target Aβ Plaques

One of the pathological hallmarks
of Alzheimer’s disease
is the presence of amyloid-β plaques in the brain and the major
constituent of these plaques is aggregated amyloid-β peptide.
New thiosemicarbazone-pyridylhydrazine based ligands that incorporate
functional groups designed to bind amyloid-β plaques have been
synthesized. The new ligands form stable four coordinate complexes
with a positron-emitting radioactive isotope of copper, 64Cu. Two of the new CuII complexes include a functionalized
styrylpyridine group and these complexes bind to amyloid-β plaques
in samples of post-mortem human brain tissue. Strategies to increase
brain uptake by functional group manipulation have led to a 64Cu complex that effectively crosses the blood-brain barrier in wild-type
mice. The new complexes described in this manuscript provide insight
into strategies to deliver metal complexes to amyloid-β plaques.