Extended-linear polymeric contrast agents, and synthesizing methods, for medical imaging
OwnerEgidijus Edward Uzgiris, Terence Michael Barnhartinventors
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Abstract
Linear extended polymeric paramagnetic chelates for use as MRI contrast agents are synthesized by conjugating DTPA chelator moieties to higher than 90% of the monomer residues of the polyamino acid backbone chain. The resulting polymer can be labeled with Gd, since each chelator moiety holds a Gd ion, and the resulting conformation is of an unfolded, extended linear type, capable of entering small pores and moving around obstacles in the extracellular space of tissues. The efficient production of these extended polymers is critical for the application of such contrast agents to medical imaging. One such agent is a reptating polymer containing technetium-99.
Claims25
An medical imaging contrast agent comprising a poly(amino acid) backbone;
- wherein amino acid residues of said poly(amino acid) backbone are conjugated to chelator moieties that comprise poly(aminoacetic acid), and said chelator moieties interact with paramagnetic metal ions;
- and wherein said poly(amino acid) backbone is selected from the group consisting of homopolymers and copolymers;
- said homopolymers are selected from the group consisting of polyarginine, polyhistidine, polytryptophan, polyasparagine, and polyglutamine;
- said copolymers comprising repeating units selected from the group consisting of at least two amino acids selected from the group consisting of lysine, histidine, tryptophan, asparagine, and glutamine.
A medical imaging contrast agent comprising a poly(amino acid) backbone;
- wherein amino acid residues of said poly(amino acid) backbone are conjugated to chelator moieties that comprise poly(aminoacetic acid) and interact with paramagnetic metal ions;
- and wherein said poly(amino acid) backbone is a copolymer comprising at least a first amino acid selected from the group consisting of histidine, tryptophan, asparagine, and glutamine;
- and a second amino acid selected from the group consisting of glutamic acid and aspartic acid.
A medical imaging contrast agent comprising a poly(amino acid) backbone;
- wherein amino acid residues of said poly(amino acid) backbone are conjugated to chelator moieties that comprise poly(aminoacetic acid) and interact with paramagnetic metal ions;
- and wherein said poly(amino acid) backbone is a copolymer comprising at least a first amino acid selected from the group consisting of lysine, histidine, tryptophan, asparagine, and glutamine;
- and a second amino acid being aspartic acid.
A method of making a substantially extended linear polymer, said method comprising the steps of:
- dissolving a salt of a poly(amino acid) in an aqueous sodium bicarbonate solution to form a first solution of said salt of said poly(amino acid) and said sodium bicarbonate;
- cooling said first solution to a temperature of about 0° C.;
- combining a polyaminoacetic acid and at least one acid acceptor in a dipolar aprotic solvent to form a second solution;
- cooling the second solution to a temperature below about −35° C.;
- adding at least one alkylchloroformate to the second solution to form a first mixture;
- adding said first mixture to said first solution to form a second mixture;
- and
- isolating a resulting polyaminoacetic acid-substituted polymer from the second mixture.
Dependencies are inferred from the claim text.