Imaging hypoxia in vivo by controlling the electrochemistry of copper radionuclide complexes

被引:11
作者
Blower, Philip J. [1 ]
Went, Michael J.
Martin, Kath E.
Smith, Gareth E.
机构
[1] Kings Coll London, Div Imaging Sci, London WC2R 2LS, England
[2] Univ Kent, Sch Phys Sci, Canterbury, Kent, England
关键词
copper; hypoxia; PET; imaging;
D O I
10.1002/jlcr.1195
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Tissue hypoxia is a feature of cancer, heart disease and stroke, and imaging it may become clinically important. Copper-ATSM (ATSMH(2) = 2,3-butanedione bis(N-methyl)thiosemicarb-azone), labelled With (CU)-C-60, (CU)-C-62 or (CU)-C-64, is selectively taken up in hypoxic cells in vitro and in vivo by a bioreductive mechanism, and is a prototype hypoxia. imaging agent amenable to improvement. In vitro studies with several differently alkylated analogues of CuATSM show that hypoxia. selectivity is a general property of complexes with two alkyl groups at the diketone backbone, offering a range of pharmacokinetic proper-ties while retaining hypoxia. selectivity. This pharmacokinetic control affords a route to development of second-generation hypoxia imaging agents With optimized properties for different clinical applications. Combinatorial synthesis of these analogues, including asymmetric ones, is possible by combining several diketones with several thiosemicarbazides and separating the products chromatographically. Copyright (c) 2007 John Wiley & Sons, Ltd.
引用
收藏
页码:354 / 359
页数:6
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