Method of enhancing NMR imaging using chelated paramagnetic ions bound to biomolecules
First Claim
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1. A method of imaging body tissue in a patient, comprising subjecting the patient to NMR tomography and prior to performing the NMR tomography administering to the patient an effective amount of a pharmaceutical agent for affecting the relaxation times of atoms in body tissue undergoing NMR diagnosis, whereby image contrast is enhanced, said agent comprising an amount, effective to affect such relaxation times, of a paramagnetic, physiologically compatible chelate complex of an ion of a lanthanide element of atomic numbers 58-70 or of a transition metal of atomic numbers 21-29, 42, or 44, wherein said chelate complex is bound to a biomolecule effective to transport said chelate complex to a specific site in said patient;
- and a pharmaceutically acceptable carrier.
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Abstract
Agents useful for influencing the relaxation times in NMR diagnostics, contain at least one paramagnetic, physiologically compatible complex salt comprising a chelate from an open-chain or cyclic complex-forming compound containing organic nitrogen, phosphorus, oxygen and/or sulfur, and a complexed ion of the lanthanide elements of atomic number 57-70 or of the transition metals of atomic numbers 21-29, 42 and 44, and, optionally, an inorganic or organic base or acid, wherein said chelate complex is bound to a biomolecule.
262 Citations
148 Claims
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1. A method of imaging body tissue in a patient, comprising subjecting the patient to NMR tomography and prior to performing the NMR tomography administering to the patient an effective amount of a pharmaceutical agent for affecting the relaxation times of atoms in body tissue undergoing NMR diagnosis, whereby image contrast is enhanced, said agent comprising an amount, effective to affect such relaxation times, of a paramagnetic, physiologically compatible chelate complex of an ion of a lanthanide element of atomic numbers 58-70 or of a transition metal of atomic numbers 21-29, 42, or 44, wherein said chelate complex is bound to a biomolecule effective to transport said chelate complex to a specific site in said patient;
- and a pharmaceutically acceptable carrier.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
- 21. A method of enhancing NMR imageability of a patient comprising administering to the patient an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion wherein said chelate complex is bound to a biomolecule effective to transport said chelate complex to a specific site in said patient.
- 43. A method of enhancing NMR imageability of a patient comprising administering to the patient an amount, effective to enhance NMR image contrast, of a physiologically acceptable chelate complex of a paramagnetic ion having as a ligand a complexing agent containing organic nitrogen, phosphorous, oxygen or sulfur, and wherein said chelate complex is bound to a biomolecule effective to transport said chelate complex to a specific site in said patient.
- 65. A method of conducting NMR imaging comprising NMR imaging a patient to whom there has been administered an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion, wherein said chelate complex is bound to a biomolecule, effective to transport said chelate complex to a specific site in said patient, and whereby an NMR image of an enhanced contrast is obtained.
- 87. A method of conducting NMR imaging comprising NMR imaging a patient to whom there has been administered an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion having as a ligand a complexing agent containing organic nitrogen, phosphorous, oxygen or sulfur, wherein said chelate complex is bound to a biomolecule effective to transport said chelate complex to a specific site in said patient, and whereby an NMR image of enhanced contrast is obtained.
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109. A method of imaging body tissue in a patient, comprising subjecting the patient to NMR tomography and prior to performing NMR tomography administering to the patient an effective amount of a pharmaceutical agent for affecting the relaxation times of atoms in body tissues undergoing NMR diagnosis, whereby image contrast is enhanced, said agent comprising an amount, effective to affect such relaxation times, of a paramagnetic, physiologically compatible chelate complex of an ion and, as a ligand, an acyclic or cyclic complexing agent containing organic nitrogen, phosphorous, oxygen or sulfur, the complexed ion being an ion of an element of atomic numbers 21-29, 42, 44, or 58-70, and wherein said chelate complex is bound to a biomolecule effective to transport said chelate complex to a specific site in said patient;
- and a pharmaceutically acceptable carrier.
- View Dependent Claims (110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128)
- 129. A method of enhancing an NMR image, comprising obtaining an enhanced NMR image by NMR imaging a human to whom there has been administered an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion, said chelate complex being bound to a biomolecule effective to transport said chelate complex to a specific site in said patient.
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Current AssigneeBayer Schering Pharma AG (Bayer AG)
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Original AssigneeSchering Ag (Merck & Co., Inc.)
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InventorsSpeck, Ulrich, Weinmann, Hanns-Joachim, Gries, Heinz, Mutzel, Wolfgang, Pfeiffer, deceased, Heinrich, Rosenberg, Douwe, Hoyer, Georg-Alexander
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Primary Examiner(s)HOLLINDEN, GARY E
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Application NumberUS07/020,300Time in Patent Office1,555 DaysField of Search424/1.1, 424/9, 436/173, 436/806, 128/653, 128/654US Class Current424/9.34CPC Class CodesA61K 49/04 X-ray contrast preparationsA61K 49/085 conjugated systemsA61K 49/10 Organic compoundsA61K 49/103 the complex-forming compoun...A61K 49/105 the metal complex being Gd-...A61K 49/106 the complex-forming compoun...A61K 49/108 the metal complex being Gd-...A61K 49/143 the protein being an albumi...A61K 49/16 Antibodies; Immunoglobulins...A61K 49/18 characterised by a special ...A61K 49/1806 Suspensions, emulsions, col...A61K 49/1809 Micelles, e.g. phospholipid...A61K 49/1812 liposomes, polymersomes, e....C07C 323/25 the carbon skeleton being a...C07D 257/02 not condensed with other ringsC07F 9/3817 Acids containing the struct...C07F 9/386 containing hydroxy substitu...G01R 33/5601 involving use of a contrast...Y10S 436/806 Electrical property or magn...Y10T 436/24 Nuclear magnetic resonance,...
