Method of magnetic resonance imaging of the liver and spleen

• US 4,675,173 A
• Filed: 05/08/1985
• Issued: 06/23/1987
• Est. Priority Date: 05/08/1985
• Status: Expired due to Term

• Current Assignee: Nycomed A/S (Takeda Pharmaceutical Company Limited)
• Original Assignee: Molecular Biosystems, Inc (Alliance Pharmaceutical Corporation)
• Inventors: Widder, Kenneth J.
• Primary Examiner(s): Nucker, Christine M.
• Assistant Examiner(s): HOLLINDEN, GARY E
• Application Number:
  US06/732,173
• Time in Patent Office: 776 Days
• Field of Search: 424/9, 128/653, 128/654, 436/526, 436/173, 436/806, 252/62.51
• US Class Current: 424/9.322
• CPC Class Codes: A61K 49/1818 particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
• CPC Class Codes: G01R 33/5601 involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent
• CPC Class Codes: Y10S 436/806 Electrical property or magnetic property
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

A method of magnetic resonance imaging (MRI) of liver and/or spleen is provided employing encapsulated contrast agents in the form of microspheres having a biodegradeable matrix with the paramagnetic/ferromagnetic contrast agent dispersed therein. Ferromagnetic contrast agents such as magnetite are preferred. Ferromagnetic microspheres when administered intravenously segregate through the reticuloendothelial system in the liver and spleen where they reduce the T₂ relaxation time to obtain improved MR imaging.

Claims

1. The method of imaging a tumor in the liver or spleen of a human subject, comprising:

(a) parenterally administering to the human subject prior to magnetic resonance imaging (MRI) examination an aqueous suspension composed essentially of 1.5 to 8 micron diameter microspheres, said microspheres having a biodegradeable matrix with a contrast agent dispersed therein selected from the group consisting of paramagnetic and ferromagnetic contrast agents, the quantity of said microspheres administered being effective to appreciably reduce the T₂ relaxation time of the subject'"'"'s liver and/or spleen;

(b) delaying the examination until the microspheres have been segregated by the reticuloendothelial system and are concentrated in the liver and spleen; and

then

(c) carrying out an MRI examinaiton of the liver and/or spleen by T₂ imaging or mixed T₁ and T₂ imaging to obtain an image in which the normal liver or spleen tissues appear dark and the tumor appears light with distinct margins therebetween.

2. The method of claim 1 in which the micropsheres have an average size range of from 2 to 5 microns diameter.

3. The method of claim 1 in which said contrast agent is in the form of ferromagnetic particles having superparamagnetic properties.

4. The method of claim 1 in which said contrast agent is in a chelated water-soluble form.

5. The method of claim 1 in which said contrast agent is a ferromagnetic compound in the form of particles sized from 50 to 300 Angstroms.

6. The method of claim 5 in which said ferrogmagnetic compound is magnetite.

7. The method of imaging a tumor in the liver or spleen of a human subject, comprising:

(a) intravenously administering to the human subject prior to magnetic resonance imaging (MRI) examination an aqeuous suspension composed essentially of microspheres having an average size of from 2 to 5 microns diameter, said microspheres being composed of a biodegradable matrix having a ferromagnetic contrast agent dispersed therein, the quantity of said microspheres administered being effective to appreciably reduce the T₂ relaxation time of the subject'"'"'s liver and/or spleen;

(b) delaying the examination until the microspheres have been segregated by the reticuloendothelial system and are concentrated in the liver and spleen; and

then

(c) carrying out an MRI examination of the liver and/or spleen by T₂ imaging or mixed T₁ and T₂ imaging to obtain an image in which the normal liver or spleen tissues appear dark and the tumor appears light with distinct margins therebetween.

8. The method of claim 7 in which said ferromagnetic contrast agent is in the form of particles having superparamagnetic properties.

9. The method of claim 7 in which said ferromagnetic contrast agent is in a chelated water-soluble form.

10. The method of claim 7 in which said ferromagnetic contrast agent is in the form of particles sized from 50 to 300 Angstroms.

11. The method of claim 10 in which said ferromagnetic contrast agent is magnetite.

12. The method of imaging a tumor in the liver or spleen of a human subject, comprising:

(a) intravenously administering to the human subject prior to magnetic resonance imaging (MRI) examination an aqueous suspension composed essentially of 1.5 to 8 micron diameter microspheres, said microspheres having a matrix of human serum albumin with magnetite particles dispersed therein, the quantity of said micropsheres administered being effective to appreciably reduce the T₂ relaxation time of the subject'"'"'s liver and/or spleen;

(b) delaying the examination until the microspheres have been segregated by the reticuloendothelial system and are concentrated in the liver and spleen; and

then

(c) carrying out an MRI examination of the liver and/or spleen by T₂ imaging or mixed T₁ and T₂ imaging to obtain an image in which the normal liver or spleen tissues appear dark and the tumor appears light with distinct margins therebetween.

13. The method of claim 12 in which the microspheres have an average size of from 2 to 5 microns diameter, and said magnetite particles are sized from 50 to 300 Angstroms and have superparamagnetic properties.

14. The method of claim 12 in which said microspheres have an average size of from 2 to 5 microns diameter and contain from 10 to 40 parts by weight of said magnetite particles per 100 parts of sid albumin, said particles being sized from 50 to 300 Angstroms and having superparamagnetic properties, the quantity of said microspheres administered ranging from 1 to 40 milligrams per kilogram of body weight.