Hepatocyte-specific receptor-mediated endocytosis-type compositions

A method for obtaining an enhanced MR image of an organ or tissue of an animal or human subject which comprises:

• (a) administering to such a subject an effective amount of a colloidal biodegradable superparamagnetic contrast agent in a physiologically acceptable medium such that an image-enhancing amount of such contrast agent can be internalized by hepatocytes of the liver by receptor mediated endocytosis, said contrast agent comprising (1) biodegradable superparamagnetic metal oxide particles, physically or chemically joined with (2) a ligand,
• wherein such metal oxide particles:
• comprise one or more individual biodegradable superparamagnetic metal oxide crystals, and
• are capable of being biodegraded in such subject, as evidenced by a return of proton relaxation rates of the liver to preadministration levels, within 30 days of administration;
• and
• wherein such ligand:
• is capable of being recognized and internalized by hepatocytes of the liver by receptor mediated endocytosis, thereby permitting said metal oxide particles to be internalized by such hepatocytes, and
• is selected from the group consisting of (i) arabinogalactan, and (ii) a macromolecular species conjugate, which macromolecular species conjugate comprises two macromolecular species, a first macromolecular species which is arabinogalactan, and a second macromolecular species which is physically or chemically joined with the metal oxide particles and conjugated to the first macromolecular species;
• and (b) recording such MR image.

A colloidal biodegradable superparamagnetic contrast agent, said contrast agent comprising (1) biodegradable superparamagnetic metal oxide particles, physically or chemically joined with (2) a ligand,

• wherein such metal oxide particles:
• comprise one or more individual biodegradable superparamagnetic metal oxide crystals, and
• are capable of being biodegraded in such subject, as evidenced by a return of proton relaxation rates of the liver to preadministration levels, within 30 days of administration;
• and
• wherein such ligand:
• is capable of being recognized and internalized by hepatocytes of the liver by receptor mediated endocytosis, thereby making said metal oxide particles capable of being internalized by such hepatocytes, and
• is selected from the group consisting of (i) arabinogalactan, and (ii) a macromolecular species conjugate, which macromolecular species conjugate comprises two macromolecular species, a first macromolecular species which is arabinogalactan, and a second macromolecular species which is physically or chemically joined with the metal oxide particles and conjugated to the first macromolecular species.