CONJUGATES OF 19F MR IMAGING TRACERS AND CHEMOTHERAPEUTIC AGENTS FOR DRUG QUANTIFICATION AND DRUG DOSE INDIVIDUALIZATION

• US 20110123457A1
• Filed: 12/17/2010
• Published: 05/26/2011
• Est. Priority Date: 06/19/2008
• Status: Abandoned Application

• Current Assignee: University of Maryland, University of Maryland, College Park
• Original Assignee: University of Maryland, University of Maryland, College Park
• Inventors: Yu, Yihua
• Application Number:
  US12/971,768
• Publication Number:
  US 20110123457A1
• Time in Patent Office: Days
• US Class Current: 424/9.34
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 49/085 conjugated systems
• CPC Class Codes: A61K 49/124 dendrimers, dendrons, hyperbranched compounds
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A therapeutic agent formed of a magnetic resonance imaging tracer conjugated with a chemotherapeutic agent. The therapeutic agents can be used in measuring drug delivery to a target tissue. The therapeutic agents allow for therapeutic MRI, in which ¹⁹F MRI techniques are used to detect, monitor, evaluate, and/or adjust chemotherapeutic drug dosage levels in a patient or a targeted tissue thereof.

Claims

1. A composition, comprising a ¹⁹F magnetic resonance (MR) imaging tracer conjugated with a chemotherapeutic agent, wherein the composition is detectable by ¹⁹F MRI.

2. The composition according to claim 1, wherein the MR imaging tracer comprises a fluorocarbon.

3. The composition according to claim 1, further comprising a dual-nuclei imaging agent.

4. The composition according to claim 1, wherein the chemotherapeutic agent comprises a prodrug.

5. The composition according to claims 1, wherein the MR imaging tracer is conjugated to a plurality of chemotherapeutic agents, the MR imaging tracer comprises a branching module including a plurality of branching units, and each of the branching units is conjugated to one of the plurality of chemotherapeutic agents.

6. The composition according to claim 5, wherein the branching module comprises iminodicarboxylic acid.

7. The composition according to claim 5, wherein the MR imaging tracer comprises a hydrophilicity enhancing module connecting each of the plurality of branching units to the one of the plurality of chemotherapeutic agents.

8. The composition according to claim 7, wherein the hydrophilicity enhancing module comprises oligo-oxyethylene.

9. The composition according to claim 1, comprising the structure:

10. The composition according to claim 9, wherein each of R₁₁, R₁₂, R₁₃, R₂₁, R₂₂, R₂₃, R₃₁, R₃₂, and R₃₃ is CF₃.

11. The composition according to claim 9, wherein R₄ comprises the structure:

12. The composition according to claim 11, wherein the amide comprises the structure:

13. The composition according to claim 11, wherein the amide comprises the iminocarboxylic acid structure:

14. The composition according to claim 9, comprising the structure:

15. The composition according to claim 9, wherein X comprises:

16. The composition according to claim 1, comprising the structure:

17. The composition according to claim 16, wherein at least one X comprises:

18. The composition according to claim 1, further comprising a pharmaceutically acceptable carrier.

19. A method of administering a drug treatment to a mammal, the method comprising:

administering to the mammal a dose of the composition of claim 1; and

measuring an amount of the composition in a tissue or organ of the mammal using ¹⁹F magnetic resonance imaging (MRI).

20. The method according claim 19, wherein the chemotherapeutic agent comprises a prodrug, and the imaging tracer is cleaved from the chemotherapeutic agent during conversion of the prodrug to an active drug, and further comprising:

administering to the mammal a plurality of doses of the composition;

intermittently conducting a plurality of measurements of the amount of the prodrug in the tissue or organ of the mammal using MRI;

determining an optimal dose of the prodrug or active drug for the mammal using the plurality of measurements; and

adjusting a dosage of the composition based upon one or more of the plurality of measurements.