Diagnostic Imaging Agents for Alzheimer鈥檚 Disease: Copper Radiopharmaceuticals that Target A尾 Plaques

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• 作者：James L. Hickey ; SinChun Lim ; David J. Hayne ; Brett M. Paterson ; Jonathan M. White ; Victor L. Villemagne ; Peter Roselt ; David Binns ; Carleen Cullinane ; Charmaine M. Jeffery ; Roger I. Price ; Kevin J. Barnham ; Paul S. Donnelly
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：October 30, 2013
• 年：2013
• 卷：135
• 期：43
• 页码：16120-16132
• 全文大小：583K
• 年卷期：v.135,no.43(October 30, 2013)
• ISSN：1520-5126

文摘

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 Cu^II 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.