Rhenium and technetium complexes of thioamide derivatives of pyridylhydrazine that bind to amyloid-β plaques

Age-associated deposition of amyloid-beta in cerebral blood vessels, a condition referred to as cerebral amyloid angiopathy, can contribute to stroke and dementia. This research aimed to design new radioactive technetium-99 m complexes that bind to amyloid-beta plaques that have the potential to assist in diagnosis of cerebral amyloid angiopathy using single-photon-emitted computed tomography (SPECT) imaging. Six new pyridylthiosemicarbazide ligands containing either benzofuran or styrylpyridyl functional groups that are known to selectively bind to amyloid plaques were prepared. Non-radioactive isotopes of technetium are not available so rhenium was used as a surrogate for exploratory chemistry. The new ligands were used to prepare well-defined [Re-oxo](3+) complexes where two pyridylthiosemicarbazide ligands were coordinated to a single metal ion to give bivalent complexes with two amyloid-beta targeting functional groups. The interaction of the [Re-oxo](3+) complexes with synthetic amyloid-beta(1-42) and with amyloid plaques in human brain tissue was investigated. Two ligands were selected to develop methods to prepare their [Tc-99m-oxo](3+) complexes at the tracer level. These technetium-99 m complexes are likely to be isostructural to their rhenium-oxo analogues.