Synthesis and in vitro evaluation of three 99mTc-labeled hydroxamamide-based ligands as markers for hypoxic cells

Three new hydroxamamide derivatives with different lipophilicity, N'-hydroxy-N-methyl-3-(4-nitro-1H-imidazol-1-yl)propanamidine, N-butyl-N'-hydroxy-3-(4-nitro-1H-imidazol-1-yl)propanamidine, and N'-hydroxy-3-(4-nitro-1H-imidazol-1-yl)-N-octadecyl propanamidine were easily synthesized and labeled with technetium-99m as markers for hypoxic cells. The results of in vitro experiment indicate that the accumulation of three (99m)Tc-complexes steadily increases with time in hypoxic cells, but fluctuates with time and has no fixed trend in aerobic cells; the complex with higher lipophilicity shows more uptake in cells; and the effect of lipophilicity of the (99m)Tc-complexes on the hypoxic/aerobic difference can be neglected. (C) 2009 Elsevier Ltd. All rights reserved.