Design and characterization of a polymeric MRI contrast agent based on PVA for in vivo living-cell tracking.

A novel water-soluble MRI contrast agent for in vivo living cell tracking was developed. Unlike the conventional in vivo cell tracking system based on superparamagnetic iron oxide beads, the newly developed contrast agent is eliminated from the body when the contrast agent exits the cells upon cell death, which makes living cell tracking possible. The contrast agent is composed of gadolinium chelates (Gd-DOTA) and a water-soluble carrier, poly(vinyl alcohol) (PVA), which is known to interact with cells and tissues very weakly. Since the Gd-PVA was not taken up by cells spontaneously, the electroporation method was used for cell labeling. The delivered Gd-PVA was localized only in the cytosolic compartment of growing cells with low cytotoxicity and did not leak out of the living cells for long periods of time. This stability may be due to the weak cell-membrane affinity of Gd-PVA, and did not affect cell proliferation at all. After cell labeling, signal enhancement of cells was observed in vitro and in vivo. These results indicate that Gd-PVA can visualize only the living cells in vivo for a long period of time, even in areas deep within large animal bodies.