Method for diagnostically imaging lesions in the brain inside a blood-brain barrier

• US 5,059,415 A
• Filed: 02/21/1989
• Issued: 10/22/1991
• Est. Priority Date: 02/21/1989
• Status: Expired due to Fees

• Current Assignee: Oregon State University (Oregon University System)
• Original Assignee: Oregon State University (Oregon University System)
• Inventors: Neuwelt, Edward A.
• Primary Examiner(s): Hollrah, Glennon H.
• Assistant Examiner(s): Hollinden, Gary E.
• Application Number:
  US07/314,940
• Time in Patent Office: 973 Days
• Field of Search: 424/9, 436/173, 436/806, 128/653 F, 128/653 A, 128/654, 514/23
• US Class Current: 424/9.34
• CPC Class Codes: A61K 49/06 Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
• CPC Class Codes: A61K 49/16 Antibodies; Immunoglobulins; Fragments thereof
• 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

An improved method for diagnosing and characterizing brain lesions is described which first involves chemically modifying the blood-brain barrier (BBB) in order to increase BBB permeability. Thereafter, a chemical agent (e.g. monoclonal antibody) is introduced which binds directly, specifically and exclusively to brain lesons. The chemical has a label attached thereto (e.g. gadolinium-DTPA). The chemical agent and label localize in regions of brain lesion proliferation. Thereafter, the brain is quantitatively analyzed to determine the amount of labeling agent present, preferably using magnetic resonance imaging techniques. This procedure enables the accurate analysis of brain lesions, and represents an advance in the art of diagnostic imaging.

Claims

1. A method for diagnostically imaging a naturally occurring brain lesion in a warm-blooded animal having a brain situated inside a blood-brain barrier having an ambient permeability level, the method comprising the steps:

administering a first chemical agent to said animal at a location outside the blood-brain barrier, where the first chemical agent is capable of increasing the permeability of the blood-brain barrier from the ambient level to an elevated permeability level;

administering a second chemical agent to said animal at a location outside the blood-brain barrier following the administration of said first chemical agent, said second chemical agent being capable of binding preferentially to a naturally occurring brain lesion and of passing through the animal'"'"'s blood-brain barrier to the brain lesion when the blood-brain barrier is at the elevated permeability level but not at the ambient permeability level, said second chemical agent comprised of molecules having at least one labeling agent attached to each said molecule;

allowing the animal to eliminate any amount of the second chemical agent with attached labeling agent not bound to said brain lesion; and

analyzing said brain of said animal for the presence of said labeling agent bound to the brain lesion in order to determine the size, type, and character of said brain lesion.

2. The method of claim 1 wherein said first chemical agent comprises a material selected from the group consisting of mannitol, arabinose, and glycerol.

3. The method of claim 1 wherein said second chemical agent comprises a monoclonal antibody.

4. The method of claim 1 wherein said labeling agent comprises gadolinium-DTPA.

5. The method of claim 4 wherein the step of analyzing said brain of said animal for the presence of said labeling agent comprises conducting a magnetic resonance imaging scan of said brain.

6. A method for diagnostically imaging a naturally occurring brain lesion in a warm-blooded animal having a blood-brain barrier having an ambient permeability level, the method comprising the steps of:

administering a first chemical agent to said animal at a location outside the blood-brain barrier, where the first chemical agent is capable of increasing the permeability of the blood-brain barrier from the ambient level to an elevated permeability level and comprises a hypertonic solution of a material selected from the group consisting of mannitol, arabinose, and glycerol;

administering a second chemical agent to said animal at a location outside the blood-brain barrier following administration of said first chemical agent, said second chemical agent being capable of binding preferentially to a naturally occurring brain lesion tissues and of passing through the animal'"'"'s blood-brain barrier to the brain lesion when the blood-brain barrier is at the elevated permeability level but not at the ambient permeability level, where said second chemical agent comprises monoclonal antibody molecules each having at least one labeling agent comprising gadolinium-DTPA attached to each said monoclonal antibody molecule;

allowing the animal to eliminate any amount of the second chemical agent with attached labeling agent not bound to said brain lesion; and

analyzing said brain of said animal for the presence of said labeling agent bound to the brain lesion in order to determine the size, type, and character of said brain lesion, said analyzing comprising the step of conducting a magnetic resonance imaging scan of said brain.