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

• Published in: Journal of biological inorganic chemistry Vol. 23; no. 7; pp. 1139 - 1151
• Main Authors: Fletcher, Scott P., Noor, Asif, Hickey, James L., McLean, Catriona A., White, Jonathan M., Donnelly, Paul S.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2018; Springer Nature B.V
• Subjects: Alison Butler: Papers in Celebration of Her 2018 ACS Alfred Bader Award in Bioorganic or Bioinorganic Chemistry; Benzofuran; Biochemistry; Biomedical and Life Sciences; Blood vessels; Cerebral amyloid angiopathy; Computed tomography; Dementia disorders; Inorganic chemistry; Isotopes; Life Sciences; Ligands; Metal ions; Microbiology; Neuroimaging; Original Paper; Rhenium; Senile plaques; Single photon emission computed tomography; Technetium; Technetium; Rhenium; Amyloid-β; Imaging
• ISSN: 0949-8257; 1432-1327
• DOI: 10.1007/s00775-018-1590-4

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-β 1-42 and with amyloid plaques in human brain tissue was investigated. Two ligands were selected to develop methods to prepare their [ 99m Tc-oxo] 3+ complexes at the tracer level. These technetium-99 m complexes are likely to be isostructural to their rhenium-oxo analogues. Graphical abstract