In vitro and in vivo imaging of Phase I xenobiotic-metabolizing enzymes

This tutorial review provides a summary and discussion of recent advances in chemosensors that fluorescently respond to the enzyme systems involved in Phase I xenobiotic metabolism, including in vitro and in vivo imaging applications on biomedical models. This review includes Phase I enzyme systems such as cytochrome P450, monoamine oxidase, nitroreductases, aldehyde dehydrogenases, esterases, amidases, glycosidases. The enzy-matic activities belong to oxidation, reduction, and hydrolysis reactions and show metabolic ability to diverse chemicals. These activities may be closely related to alterations in various pathophysiological processes in the human body, and their roles in drug metabolism are well known. Therefore, the enzyme-directed imaging techniques toward both in vitro and in vivo living systems have emerged as promising diagnostic modalities. In particular, fluorescent chemosensors activated through xenobiotic metabolism would serve as useful tools to study live biosystems, such as in situ monitoring and high-throughput drug screening, owing to their spatio-temporal responses with high sensitivity, selectivity, and rapidity. Current advances in detection strategies and validated in vitro and in vivo biomedical models for xenobiotic metabolism are highlighted. A brief discussion of the current and future challenges follows.