What is the mechanism for the activation and binding of Hypoxyprobe -1 to hypoxic cells?
Varghese et al. were first to show that hypoxic cells activate and bind 2-nitroimidazole compounds (1). Subsequent studies by a number of investigators contributed to an understanding of the overall mechanism of bioreductive activation and binding of 2-nitroimidazoles (2-7). The current view of the metabolism of Hypoxyprobe -1 is summarized in the scheme below. In vivo, Hypoxyprobe -1 is subject to oxidative metabolism leading to easily excretable N-oxide, sulfate and glucuronate derivatives (ST = sulfotransferase; GT = glucuronly transferase). These pathways do not appear to interfere with the utility of Hypoxyprobe -1 at the doses used for hypoxia marking (7). Oxygen competes for the addition of the first electron to Hypoxyprobe -1 and it is believed that this competition accounts for the oxygen dependence of 2-nitroimidazole reductive activation and binding. The chemical structure of adducts to proteins is not known with certainty but the available evidence supports the idea that th
