Methods and compositions for magnetic resonance imaging comprising superparamagnetic ferromagnetically coupled chromium complexes
First Claim
1. A composition of matter comprisinga superparamagnetic polyatomic metal atom complex, containing plural paramagnetic metal atoms which are intramolecularly ferromagnetically coupled, and including bridging ligands bound to said paramagnetic metal atoms, said polyatomic metal complex consisting essentially of four Cr(III) atoms which are bound to a central tetrahedral sulfur atom and are octahedrally coordinated by bridging ligands,said polyatomic complex being bound to or associated with:
- a biocompatible and at least substantially water-soluble anionic carbohydrate, oligosaccharide, polysaccharide, or glycosaminoglycan carrier;
said carrier having repeating hydrophilic units which contain covalently bound available reactive groups selected from the group consisting of hydroxyl, carbonyl, aldehyde, carboxylate, sulfate, phosphate and amine groups,wherein said polyatomic metal atom complex is in a molar ratio to individual repeating units of said carrier of between about 1;
2 and about 1;
25.
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Accused Products
Abstract
Improved compositions and methods for selective access to tumor regions (or other regions of abnormal endothelial properties). This capability provides powerful contrast-enhancement agents for nuclear magnetic resonance imaging. A polyatomic complex which includes intramolecular ferromagnetic coupling between metal atoms is associated with a polymer or microsphere carrier matrix which will bind to endothelial determinants. A solution containing this carrier complex is injected into a human (or other) body to be imaged. The carrier complex will preferentially extravasate at locations where the blood vessel walls have increased porosity or microvascular surface changes, and especially at tumor sites. Thus, the changes in relaxation time induced by the presence of the carrier complex will provide a high-gain marker for magnetic resonance imaging.
Multiple superparamagnetic polyatomic complexes are described, including novel complexes which include acetate and glycinate bridging ligands with a polyatomic metal-atom-complex core.
92 Citations
29 Claims
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1. A composition of matter comprising
a superparamagnetic polyatomic metal atom complex, containing plural paramagnetic metal atoms which are intramolecularly ferromagnetically coupled, and including bridging ligands bound to said paramagnetic metal atoms, said polyatomic metal complex consisting essentially of four Cr(III) atoms which are bound to a central tetrahedral sulfur atom and are octahedrally coordinated by bridging ligands, said polyatomic complex being bound to or associated with: -
a biocompatible and at least substantially water-soluble anionic carbohydrate, oligosaccharide, polysaccharide, or glycosaminoglycan carrier; said carrier having repeating hydrophilic units which contain covalently bound available reactive groups selected from the group consisting of hydroxyl, carbonyl, aldehyde, carboxylate, sulfate, phosphate and amine groups, wherein said polyatomic metal atom complex is in a molar ratio to individual repeating units of said carrier of between about 1;
2 and about 1;
25. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
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22. A method for magnetic resonance imaging, comprising the steps of:
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identifying a living vertebrate animal to be imaged; introducing into the blood stream or body cavity of said animal a diagnostically effective amount of a diagnostic imaging agent comprising an at least substantially water-soluble anionic carrier with a molecular weight of greater than about 1,000 Daltons, and also includes plural superparamagnetic polyatomic metal atom complexes associated with said carrier, each of polyatomic metal atom complexes including plural paramagnetic metal atoms which are intramolecularly ferromagnetically coupled metal, said polyatomic metal complexes consisting essentially of four Cr(III) atoms which are bound to a central tetrahedral sulfur atom and are octahedrally coordinated by bridging ligands; applying to said animal a strong magnetic field which includes a gradient; and applying to at least a portion of said animal an electromagnetic perturbation field at a radio frequency corresponding to a resonant frequency of a predetermined atomic nucleus at a magnetic field strength which falls within a range of field strengths applied to said animal by said strong magnetic field, and measuring radio frequency emissions to define a spatial map of magnetic resonance characteristics within tissues of said animal. - View Dependent Claims (23, 24, 25, 26)
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27. A composition of matter comprising
a superparamagnetic polyatomic metal atom complex, containing plural paramagnetic metal atoms which are intramolecularly ferromagnetically coupled, and including bridging ligands bound to said paramagnetic metal atoms, said polyatomic metal complex consisting essentially of four Cr(III) atoms which are bound to a central tetrahedral sulfur atom and are octahedrally coordinated by bridging ligands, said polyatomic complex being bound to or associated with: -
a biocompatible and at least substantially water-soluble anionic carbohydrate, oligosaccharide, polysaccharide, or glycosaminoglycan carrier; said carrier having repeating hydrophilic units which contain covalently bound available reactive groups selected from the group consisting of hydroxyl, carbonyl, aldehyde, carboxylate, sulfate, phosphate and amine groups, wherein said carrier is complementary to determinants of vertebrate endothelia or epithelia, wherein said polyatomic metal atom complex is in a molar ratio to individual repeating units of said carrier of between about 1;
2 and about 1;
25.
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28. A composition of matter comprising
a superparamagnetic polyatomic metal atom complex, containing plural paramagnetic metal atoms which are intramolecularly ferromagnetically coupled, and including bridging ligands bound to said paramagnetic metal atoms, said polyatomic metal complex consisting essentially of four Cr(III) atoms which are bound to a central tetrahedral sulfur atom and are octahedrally coordinated by bridging ligands, said polyatomic complex being bound to or associated with: -
a biocompatible and at least substantially water-soluble carbohydrate, oligosaccharide, polysaccharide, or glycosaminoglycan carrier; said carrier having repeating hydrophilic units which contain covalently bound available reactive carboxylate or sulfate groups, wherein said polyatomic metal atom complex is in a molar ratio to individual repeating units of said carrier of between about 1;
2 and about 1;
25.
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29. A composition of matter comprising
a superparamagnetic polyatomic metal atom complex, containing plural paramagnetic metal atoms which are intramolecularly ferromagnetically coupled, and including bridging ligands bound to said paramagnetic metal atoms, said polyatomic metal complex consisting essentially of four Cr(III) atoms which are bound to a central tetrahedral sulfur atom and are octahedrally coordinated by bridging ligands, said polyatomic complex being bound to or associated with: -
a biocompatible and at least substantially water-soluble carbohydrate, oligosaccharide, polysaccharide, or glycosaminoglycan carrier; said carrier having repeating hydrophilic units which contain covalently bound available reactive groups selected from the group consisting of carboxylate and sulfate, wherein said carrier is complementary to determinants of vertebrate endothelia or epithelia, wherein said polyatomic metal atom complex is in a molar ratio to individual repeating units of said carrier of between about 1;
2 and about 1;
25.
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Specification