Vascular magnetic imaging method and agent comprising biodegradeable superparamagnetic metal oxides

A biodegradable superparamagnetic metal oxide comprising aggregates of individual biodegradable superparamagnetic hydrated metal oxide crystals associated with a macromolecular species, said metal oxide (i) having an individual crystal diameter of about 500 angstroms or less and aggregates with an overall mean diameter of about 4000 angstroms or less, as measured by light scattering methods;

• (ii) having a magnetic saturation between about 5 and about 90 EMU/g of metal oxide at approximately 300.degree. K. and a magnetic squareness of less than 0.1, characteristic of a superparamagnetic metal oxide crystal;
• (iii) being capable of retaining anions in solution;
• characteristic of paramagnetic metal oxyhydroxides;
• (iv) being capable of producing proton relaxivity values, R.sub.1 and R.sub.2, greater than or equal to about 10.sup.4 and 10.sup.5 M.sup.-1 sec.sup.-1, respectively, characteristic of sonicated superparamagnetic metal oxide crystal aggregates;
• about (v) capable of being biodegraded in a subject within about two weeks or less after administration, as evidenced by a return of the proton relaxation rates of affected tissue of such subject to preadministration levels.

A sterilizable biodegradable superparamagnetic fluid which comprises:

• (a) a biodegradable superparamagnetic metal oxide comprising aggregates of individual biodegradable superparamagnetic hydrated metal oxide crystals, said metal oxide (i) having an individual crystal diameter of about 500 angstroms or less and aggregates with an overall mean diameter of about 4000 angstroms or less, as measured by light scattering methods;
• (ii) having a magnetic saturation between about 5 and about 90 EMU/g of metal oxide at approximately 300.degree. K. and a magnetic squareness of less than 0.1, characteristic of a superparamagnetic metal oxide crystal;
• (iii) being capable of retaining anions in solution, characteristic of paramagnetic metal oxyhydroxides;
• (iv) being capable of producing proton relaxivity values, R.sub.1 and R.sub.2, greater than or equal to about 10.sup.4 and 10.sup.5 M.sup.31 1 sec.sup.-1, respectively, characteristic of sonicated superparamagnetic metal oxide crystal aggregates;
• and (v) capable of being biodegraded in a subject within about two weeks or less after administration, as evidenced by a return of the proton relaxation rates of affected tissue of such subject to preadministration levels;
• and
• (b) a physiologically acceptable medium.

A sterilizable biodegradable superparamagnetic fluid which comprises:

• (a) a biodegradable superparamagnetic metal oxide comprising aggregates of individual biodegradable superparamagnetic hydrated metal oxide crystals associated with a macromolecular species, said metal oxide (i) having an individual crystal diameter of about 500 angstroms or less and aggregates with an overall mean diameter of about 4000 angstroms or less, as measured by light scattering methods;
• (ii) having a magnetic saturation between about 5 and about 90 EMU/g of metal oxide at approximately 300.degree. K. and a magnetic squareness of less than 0.1, characteristic of a superparamagnetic metal oxide crystal;
• (iii) being capable of retaining anions in solutions, characteristic of paramagnetic metal oxyhydroxides:
• (iv) being capable of producing proton relaxivity values, R.sub.1 and R.sub.2, greater than or equal to about 10.sup.4 and 10.sup.5 M.sup.31 1 sec.sup.31 1, respectively, characteristic of sonicated superparamagnetic metal oxide crystal aggregates;
• and (v) capable of being biodegraded in a subject within about two weeks or less after administration, as evidenced by a return of the proton relaxation rates of affected tissue of such subject to preadministration levels;
• and
• (b) a physiologically acceptable medium.

An autoclavable biodegradable superparamagnetic fluid which comprises:

• (a) a biodegradable superparamagnetic iron oxide comprising aggregates of individual biodegradable superparamagnetic hydrated iron oxide crystals associated with dextran, said meal oxide (i) having an individual crystal diameter of about 500 angstroms or less and aggregates with an overall mean diameter of about 4000 angstroms or less, as measured by light scattering methods;
• (ii) having a magnetic saturation between about 5 and about 90 EMU/g of iron oxide at approximately 300.degree. K. and a magnetic squareness of less than 0.1, characteristic of a superparamagnetic iron oxide crystal;
• (iii) being capable of retaining anions in solutions, characteristic of paramagnetic iron oxyhydroxides;
• (iv) being capable of producing proton relaxivity values, R.sub.1 and R.sub.2, greater than or equal to about 10.sup.4 and 10.sup.5 M.sup.-1 sec.sup.31 1, respectively, characteristic of sonicated superparamagnetic iron oxide crystal aggregates;
• and (v) capable of being biodegraded in a subject within about two weeks or less after administration, as evidenced by a return of the proton relaxation rates of affected tissue of such subject to preadministration levels;
• and
• (b) an aqueous citrate buffer.