Multimeric dual-modality breast cancer diagnostic agents

• US 9,873,711 B2
• Filed: 12/21/2015
• Issued: 01/23/2018
• Est. Priority Date: 09/11/2012
• Status: Active Grant

• Current Assignee: Preeti Misra
• Original Assignee: Preeti Misra
• Inventors: Misra, Preeti
• Primary Examiner(s): Jarrell, Noble E
• Application Number:
  US14/975,854
• Publication Number:
  US 20160168178A1
• Time in Patent Office: 764 Days
• Field of Search: None
• CPC Class Codes: A61K 47/547 Chelates, e.g. Gd-DOTA or Zinc-amino acid chelates; Chelate-forming compounds, e.g. DOTA or ethylenediamine being covalently linked or complexed to the pharmacologically- or therapeutically-active agent
• CPC Class Codes: A61K 49/0021 the fluorescent group being a small organic molecule
• CPC Class Codes: A61K 49/10 Organic compounds
• CPC Class Codes: A61K 49/108 the metal complex being Gd-DOTA
• CPC Class Codes: C07F 9/5728 condensed with carbocyclic rings or carbocyclic ring systems
• CPC Class Codes: C07F 9/6524 having four or more nitrogen atoms as the only ring hetero atoms
• CPC Class Codes: C07F 9/6558 containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system

Abstract

The present invention describes dual-modality probes. In particular, the present invention discloses hydroxyapatite specific multimeric bisphosphonate dual-modality MRI and optical probes.

Claims

1. A method of making a dual-modality probe, said method comprising:

(a) providing an organic chelating ligand, wherein said organic chelating ligand selected from the group of;

2. The method of claim 1, wherein said trifunctional linker moiety is amino acid, polymer, or dendrimer.

3. The method of claim 1, wherein said metal ion is selected from the group consisting of Cu, Fe, In, Mn, Tm, Yb, Y, Gd and Eu.

4. The method of claim 1, wherein said metal ion and said near infrared fluorophore are conjugated for concurrent magnetic resonance and near infrared optical imaging.

5. The method of claim 1, wherein said bisphosphonate is selected from the group consisting of alendronate, incadronate, neridronate, olpadronate, pamidronate, risedronate, and zoledronate.

6. The method of claim 1, wherein said bisphosphonate is selected from the group consisting of:

7. A method of making a dual-modality probe, said method comprising:

(a) reacting a bisphosphonate with a trifunctional linker moiety to result in a trifunctional linker moiety conjugated bisphosphonate, wherein said bisphosphonate and said trifunctional linker moiety are connected by amide bonds;

(b) deprotecting one or more functional groups on said trifunctional linker moiety conjugated bisphosphonate to yield one or more free functional groups;

(c) conjugating a near infrared fluorophore to result in a near infrared containing trifunctional linker moiety conjugated bisphosphonate carboxylic acid precursor, wherein said near infrared fluorophore and said trifunctional linker moiety are connected by amide bonds, wherein said near infrared fluorophore is selected from the group consisting of IRDye 78, IRDye 700DX, VivoTag-S 750, VivoTag 800, VivoTag-S 680, DY-750, DY-682, DY-675, Cypate, Cy7, Alexa Fluor 750, and Alexa Fluor 68;

(d) providing a metal chelate, wherein said metal chelate selected from the group of;

8. The method of claim 7, wherein said trifunctional linker moiety is amino acid, polymer, or dendrimer.

9. The method of claim 7, wherein M is selected from the group consisting of Cu, Fe, In, Mn, Tm, Yb, Y, Gd, and Eu.

10. The method of claim 7, wherein said dual-modality probe is in a form of pharmaceutically acceptable salts, hydrates, and solvates.

11. The method of claim 7, wherein said bisphosphonate is selected from the group consisting of alendronate, incadronate, neridronate, olpadronate, pamidronate, risedronate, and zoledronate.

12. The method of claim 7, wherein said bisphosphonate is selected from the group consisting of: