Copper bis(thiosemicarbazone) complexes as hypoxia imaging agents: structure-activity relationships

Dearling, Jason L. J. and Lewis, Jason S. and Mullen, Gregory E. D. and Welch, Michael J. and Blower, Philip J. (2002) Copper bis(thiosemicarbazone) complexes as hypoxia imaging agents: structure-activity relationships. Journal of Biological Inorganic Chemistry, 7 (3). pp. 249-259. ISSN 0949-8257 . (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Copper(II) bis(thiosemicarbazone) complexes labelled with Cu-60/62/64 are useful radiopharmaceuticals for imaging blood flow and hypoxic tissues in vivo. The aim of this study was to identify structure-activity relationships within a series of analogues with different alkyl substitution patterns in the ligand, in order to design improved hypoxia imaging agents and elucidate hypoxia selectivity mechanisms. Thirteen such complexes were synthesised and characterised spectroscopically and electrochemically. The uptake of each (labelled with Cu-64) in EMT6 tumour cells in vitro under normoxic and hypoxic conditions was studied. All complexes were taken up efficiently into cells, and some showed strong hypoxia selectivity, which was highly correlated with the Cu(II/I) redox potential. Redox potentials at the low end of the range were found to be essential for hypoxia selectivity. In turn, the redox potential was strongly correlated with alkyl substitution pattern, and the most important determinant of the redox potential was the number of alkyl groups on the diimine backbone of the ligand. Several complexes in the series warrant further evaluation as hypoxia imaging agents. The radioactivity uptake/release behaviour in the cells provides insight into possible mechanisms, and a model for hypoxia-selective intracellular trapping is discussed.

Item Type: Article
Additional information: 0949-8257 (Print) Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.
Uncontrolled keywords: radiopharmaceutical; imaging agents; copper bis(thiosemicarbazone); hypoxia; redox potential
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: Sue Davies
Date Deposited: 17 Sep 2008 11:58
Last Modified: 11 Jun 2014 13:41
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