Biodegradable computed tomography contrast agents
Biodegradable computed tomography (CT) contrast agents comprising a polyiodinated aryl contrast agent that is crosslinked by an organic disulfide are described herein. The contrast agents can be used to image a tissue region by administering an effective amount of the biodegradable CT contrast agent to a subject, allowing a sufficient amount of time for the biodegradable CT contrast agent to enter the tissue region, and performing x-ray computed tomography imaging of the tissue region of the subject.
1. A biodegradable macromolecular computed tomography (CT) contrast agent comprising a polyiodinated aryl contrast agent having a structure according to formula I:
wherein P is an organic disulfide, R 1 is a carboxyl or carboxamide group, and R 2 is a an amine, a lower alkyl group, or an amine-bound water soluble polymer or oligomer, and n is from 2 to 10,000 or a structure according to formula II:
wherein P is an organic disulfide, R 1 is a carboxyl or carboxamide group, and R 2 is a an amine, a lower alkyl group, or an amine-bound water soluble polymer or oligomer, R 3 is a lower alkylene or alkylene ether group, and n is from 2 to 10,000.
2. The biodegradable macromolecular CT contrast agent of claim 1 , wherein the polyiodinated aryl contrast agent is PEGylated.
3. The biodegradable macromolecular CT contrast agent of claim 1 , wherein R 2 is an amine.
4. The biodegradable macromolecular CT contrast agent of claim 1 , wherein R 1 is a carboxamide group.
5. The biodegradable macromolecular CT contrast agent of claim 1 , wherein the contrast agent has a structure according to formula III:
wherein R is a water soluble polymer or oligomer, and n is from 2 to 10,000.
6. The biodegradable macromolecular CT contrast agent of claim 1 , wherein the contrast agent has a structure according to formula IV:
wherein R is a water soluble polymer or oligomer and n is from 2 to 10,000.
7. A method for imaging a tissue region of a subject comprising:
(a) administering an effective amount of a biodegradable macromolecular computed tomography (CT) contrast agent according to claim 1 to the subject;
(b) allowing a sufficient amount of time for the macromolecular biodegradable CT contrast agent to enter the tissue region; and
(c) performing x-ray computed tomography imaging of the tissue region of the subject.
8. The method of claim 7 , wherein
R 2 is a an amine.
9. The method of claim 7 , wherein R 1 is a carboxamide group.
10. The method of claim 7 wherein the biodegradable macromolecular CT contrast agent has a structure according to formula III:
wherein R is a water soluble polymer or oligomer, and n is from 2 to 10,000.
11. The method of claim 7 , wherein the biodegradable macromolecular CT contrast agent has a structure according to formula IV:
wherein R is a water soluble polymer or oligomer, and n is from 2 to 10,000.
12. The method of claim 7 wherein the tissue region is a blood vessel.
13. The method of claim 7 , wherein the tissue region is a tumor.
14. A method of making a biodegradable computed tomography (CT) contrast agent, comprising the steps of:
(a) reacting pegylated or non-pegylated 5-amino-2,4,6-triiodoisophthalic acid (ATIPA) with thionyl chloride to provide an diacyl chloride polyiodinated aryl group; and
(b) polymerizing the diacyl chloride iodinated aryl group with an organic disulfide to provide a polyiodinated aryl contrast agent that is crosslinked by an organic disulfide.
15. The method of claim 14 , wherein the dicarboxyl polyiodinated aryl group is 5-amino-2,4,6-triiodoisophthalic acid (ATIPA).
16. The method of claim 14 , wherein the dicarboxyl polyiodinated aryl group is PEGylated 5-amino-2,4,6-triiodoisophthalic acid (ATIPA).