Activated clearance of a biotinylated macromolecular MRI contrast agent from the blood pool using an avidin chase

The enhancement characteristics of a contrast agent are dependent on its pharmacokinetics within the body. In the case of macromolecular contrast agents, prolonged enhancement of the blood pool is seen after the first dose, limiting opportunities for repeated injection in the same session. If the enhancement within the blood pool could be intentionally switched off, the macromolecular contrast agents could be used both to define blood volume and vessel permeability, properties that could be useful in studying angiogenesis. In the current study, the avidin-biotin system was coupled to a dendrimer-based macromolecular MRI contrast agent to switch enhancement from the blood pool to the liver. Because avidin causes rapid trapping of the contrast agent in the liver, the blood pool cleared within 2 min of the injection of avidin. This system can be applied to all dendrimer-based macromolecular MRI contrast agents to investigate blood volume and vascular permeability. Moreover, it permits the repeated injection of the contrast agent and the "avidin switch" during a single MR experiment.