Enzyme-activated MR Contrast Agents

Enzyme-activated MR Contrast Agents

Molecular imaging is broadly defined as the visualization of molecular and cellular processes on either a macro- or microscopic level. Because of its high spatial resolution and ability to noninvasively visualize internal organs, magnetic resonance (MR) imaging is widely believed to be an ideal platform for in vivo molecular imaging. For this reason, MR contrast agents that can detect molecular events are an active field of research. One group of compounds that has shown particular promise is enzyme-activated MR contrast agents.

Enzyme-activated MR contrast agents are compounds that cause a detectable change in image intensity when in the presence of the active form of a certain enzyme. This makes them useful for in vivo assays of enzyme activity. They are distinguished from current, clinical MR contrast agents that give only anatomical information, such as aqueous gadolinium compounds, by their ability to make molecular processes visible. Enzyme-activated contrast agents are powerful tools for molecular imaging. To date, β-galactosidase-activated contrast agents have attracted the most attention in the literature, although there no theoretical reason that other enzymes could not be used to activate contrast agents. Also, mechanisms other than enzyme activation, such as Ca2+-dependent activation, can theoretically be used.

In general, enzyme-activated agents contain a paramagnetic metal ion which can affect the T₁ or T₂ relaxation times for nearby water molecules. However, the metal ions are unable to interact with the water until an enzyme-catalyzed reaction takes place. Steric hindrance or coordination with other ions prevents water from accessing the paramagnetic center prior to the enzymatic reaction.