Abstract: This invention pertains to methods for imaging the activity of extracellular proteases in cells using the anthrax binary toxin-system to target cells expressing extracellular proteases with mutant anthrax toxin protective antigens (?PrAg) that bind to receptors on the cells and are cleaved by a specific extracellular protease expressed by the cells, and ligands that specifically bind to the cleaved ?PrAg and are linked to a moiety that is detectable by an imaging procedure. The ?PrAg proteins used in the methods comprise a protease cleavage site that is cleaved by a specific extracellular protease and is in place of the furin cleavage site of the native PrAg. The methods are useful for diagnosing and treating diseases and undesirable physiological conditions correlated with the activity of extracellular proteases, and for optimizing the therapeutic efficacy of drugs used to treat such diseases and conditions.