Bimodal star polymer architectures as fluorescent and MRI imaging reagents

• US 9,198,985 B2
• Filed: 05/21/2010
• Issued: 12/01/2015
• Est. Priority Date: 05/22/2009
• Status: Active Grant

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Harth, Eva M., Adkins, Chinessa T.
• Primary Examiner(s): HANLEY, SUSAN MARIE
• Application Number:
  US13/321,897
• Publication Number:
  US 20130029369A1
• Time in Patent Office: 2,020 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/0021 the fluorescent group being a small organic molecule
• CPC Class Codes: A61K 49/0054 Macromolecular compounds, i.e. oligomers, polymers, dendrimers
• CPC Class Codes: C08G 83/003 Dendrimers

Abstract

Disclosed are star polymers comprising a polymeric body having a core with a site-isolated chromophore and a plurality of polymer chains emanating from the core; and at least one chelating moiety bonded to at least one polymer chain. Also disclosed are bimodal contrast agents derived from star polymers and further comprising at least one metal chelated by the at least one chelating moiety. Also disclosed are methods of making and using same. Also disclosed are imaging methods employing the disclosed star polymers and/or bimodal contrast agents. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Claims

1. A bimodal contrast agent comprising:

(a) a polymeric body having a core and a plurality of polymer chains emanating from the core, wherein the polymer is a copolymer of styrene and methyl acrylate;

(b) at least one chromophore derived from 9,9-Bis(2-(2-methoxyethoxy)ethyl)ethyl)-2,7-divinylfluorene;

9,9-Dihexyl-2,7-divinylfluorene;

or 3-Hexyl-2,5-divinylthiophene within the body;

(c) at least one catechol-bearing chelating moiety bonded to at least one polymer chain; and

(d) at least one metal chelated by the at least one chelating moiety, wherein the metal is selected from Gd³⁺ and Eu³⁺,

wherein the agent is water-soluble.

2. The agent of claim 1, wherein the metal is Gd³⁺.

3. The agent of claim 1, wherein the metal is Eu³⁺.

4. The agent of claim 1, wherein the polymer has a molecular weight (M_w) of from about 1.2 to about 9 kg/mol.

5. The agent of claim 1, wherein the polymer has a polydispersity index of no more than about 1.6.

6. The agent of claim 1, wherein the polymer has a molecular weight (M_w) of from about 7.2 to about 9.3 kg/mol.

7. The agent of claim 1, wherein the polymer has a polydispersity index of no more than about 1.1.

8. The agent of claim 1, wherein the polymer has a molecular weight (M_w) of about 9 kg/mol and a polydispersity index of no more than about 1.1.

9. The agent of claim 1, further comprising at least one covalently bonded dendritic molecular transporter moiety.

10. The agent of claim 1, further comprising one or more polyoxyalkylenamine residues bonded to a polymer chain.