Degradable macromolecular magnetic resonance imaging contrast agents and methods thereof
AssigneeUniversity of Utah Research Foundation
InventorsZheng-Rong Lu, Jindrich Kopecek, Dennis L. Parker
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Abstract
Degradable macromolecular magnetic resonance imaging contrast agents for use in various diagnostic procedures, and methods for synthesizing, using and degrading these agents, are described. The macromolecule contrast agents disclosed in various aspects of this invention are degradable gadolinium compounds which show prolonged plasma retention, and enhanced permeability and retention in solid tumors, but are still capable of being rapidly cleared from the body.
Claims20
A macromolecule contrast agent comprising a compound according to the following formula:
- wherein R and R′ are independently selected from the group consisting of C1 to C18 alkyls, substituted alkyls, aryls, polyethylene glycol, saccharides, amino acids, peptides, proteins, peptide conjugates and protein conjugates, and combinations of at least two of alkyl, aryl, and polyethylene glycol groups;
- wherein X and Y are independently selected from the group consisting of amide groups, ester groups, urea groups, thiourea groups, carbonate groups, carbamate groups, ether bonds and thioether bonds;
- wherein P is selected from the group consisting of water soluble polymer chains, dendrimers, polysaccharides, peptides, proteins, polymer-peptide conjugates and polymer-protein conjugates;
- wherein n is an integer between 2 and 10,000;
- and
- wherein L is selected from the group consisting of diethylenetriaminepentaacetate (DTPA), 1,4,7,10-tetraazadodecanetetraacetate (DOTA), 1,4,7,10-tetraazadodecane-1,4,7-triacetate (DO3A), ethylenediaminetetraacetate (EDTA), 1,4,7,10-tetraazacyclotridecanetetraacetic acid (TRITA), 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA), 1,4,7,10-tetraazadodecanetetramethylacetate (DOTMA), 1,4,7,10-tetraazadodecane-1,4,7-trimethylacetate (DO3MA), N,N′,N″,N′″-tetraphosphonatomethyl-1,4,7,10-tetraazacyclododecane (DOTP), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylene methylphosphonic acid) (DOTMP), and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phenylphosphonic acid) (DOTPP).
A macromolecule contrast agent comprising a compound according to the following formula:
- wherein R and R′ are independently selected from the group consisting of C1 to C18 alkyls, substituted alkyls, aryls, polyethylene glycol, saccharides, amino acids, peptides, proteins, peptide conjugates and protein conjugates, and combinations of at least two of alkyl, aryl, and polyethylene glycol groups;
- wherein X is selected from the group consisting of amide groups, ester groups, and ether bonds;
- wherein Y is selected from the group consisting of O and NH;
- wherein n is an integer between 2 and 10,000;
- and
- wherein P is selected from the group consisting of water soluble polymer chains, dendrimers, polysaccharides, peptides, proteins, polymer-peptide conjugates and polymer-protein conjugates.
A macromolecule contrast agent comprising a compound according to the following formula:
- wherein R and R′ are independently selected from the group consisting of C1 to C18 alkyls, substituted alkyls, aryls, polyethylene glycol, saccharides, amino acids, peptides, proteins, peptide conjugates and protein conjugates, and combinations of at least two of alkyl, aryl, and polyethylene glycol groups;
- wherein X is selected from the group consisting of amide groups, ester groups, and ether bonds;
- wherein Y is selected from the group consisting of O and NH;
- wherein n is an integer between 2 and 10,000;
- and
- wherein P is selected from the group consisting of water soluble polymer chains, dendrimers, polysaccharides, peptides, proteins, polymer-peptide conjugates and polymer-protein conjugates.
A macromolecule contrast agent comprising a compound according to the following formula:
- wherein R and R′ are independently selected from the group consisting of C1 to C18 alkyls, substituted alkyls, aryls, polyethylene glycol, saccharides, amino acids, peptides, proteins, peptide conjugates and protein conjugates, and combinations of at least two of alkyl, aryl, and polyethylene glycol;
- wherein X is selected from the group consisting of amide groups, ester groups, and ether bonds;
- wherein Y is selected from the group consisting of O and NH;
- wherein n is an integer between 2 and 10,000;
- and
- wherein P is selected from the group consisting of water soluble polymer chains, dendrimers, polysaccharides, peptides, proteins, polymer-peptide conjugates and polymer-protein conjugates.
A macromolecule contrast agent comprising a compound selected from the group consisting of compounds according to the following formulae:
- wherein n is an integer between 2 and 10,000;
- and
- wherein x is an integer between 1 and 20;
- and
- wherein m is an integer between 0 and 10,000.
Dependencies are inferred from the claim text.