One of the pathological hallmarks of Alzheimer鈥檚 disease is the presence of amyloid-尾 plaques in the brain and the major constituent of these plaques is aggregated amyloid-尾 peptide. New thiosemicarbazone-pyridylhydrazine based ligands that incorporate functional groups designed to bind amyloid-尾 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-尾 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-尾 plaques.