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

Fletcher, Scott P.; Noor, Asif; Hickey, James L.; McLean, Catriona A.; White, Jonathan M.; Donnelly, Paul S.

Abstract: Age-associated deposition of amyloid-β 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-β 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-β targeting functional groups. The interaction of the [Re-oxo]3 complexes with synthetic amyloid-β1-42 and with amyloid plaques in human brain tissue was investigated. Two ligands were selected to develop methods to prepare their [99mTc-oxo]3 complexes at the tracer level. These technetium-99 m complexes are likely to be isostructural to their rhenium-oxo analogues.Graphical abstract:

RHENIUM; TECHNETIUM; THIOAMIDES; AMYLOID plaque; DEMENTIA; CEREBRAL amyloid angiopathy

Journal of Biological Inorganic Chemistry (JBIC), 2018, Vol 23, Issue 7, p1139

0949-8257

Academic Journal

10.1007/s00775-018-1590-4