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

TY - JOUR

T1 - Imaging hypoxia in vivo by controlling the electrochemistry of copper radionuclide complexes

AU - Blower, P J

AU - Went, M J

AU - Martin, K E

AU - Smith, G E

PY - 2007/4

Y1 - 2007/4

N2 - 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

AB - 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

U2 - 10.1002/jlcr.1195

DO - 10.1002/jlcr.1195

M3 - Article

VL - 50

SP - 354

EP - 359

JO - JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS

JF - JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS

IS - 5-6

ER -