Figure 2. Activatable probes for molecular imaging of disease-associated enzymes.

(A) Approaches that convert enzyme activity to an imaging readout include probes that assess substrate catalysis (top) or bind to the enzyme active site (bottom). Probes carry a dye or contrast agent and remain “OFF” prior to enzyme activation (grey star). Substrate-based probes carry an enzyme substrate and recognition motif (blue ellipse) that may be processed by active enzymes, while binding-based probes carry a chemical warhead (blue triangle) that can covalently bind to active enzymes. These probes turn “ON” to produce an imaging readout (green star) upon processing by enzymes such as proteases. (B) These probes can be used in vivo for diagnostic or intraoperative imaging (top), or ex vivo for visualization of tumor margins or for pathogen detection in clinical specimens (bottom).