Composition and methods for imaging cells

Patent metadata

Field	Value
Publication number	US-10413621-B2
Application number	US-201013502852-A
Country	US
Kind code	B2
Filing date	Oct 19, 2010
Priority date	Oct 19, 2009
Publication date	Sep 17, 2019
Grant date	Sep 17, 2019

Abstract

A composition for imaging a cell includes a first imaging probe and a second imaging probe that include respectively a first reporter moiety and a second reporter moiety. The first reporter moiety and the second reporter moiety form a signaling complex that produces a detectable signal when the first imaging probe and second imaging probe complex with first and second biomarkers of the cell.

First claim

Having described the invention, the following is claimed:

1. A composition for imaging a cell having a first biomarker and a second biomarker that is different than the first biomarker, the composition comprising:
a first imaging probe comprising a first targeting moiety that is linked to a self-immolative enzyme-activated magnetic resonance contrast agent conjugated to a biotin attachment molecule via a streptavidin linkage;

wherein O represents a coordinate metal ion and is selected from the group consisting of Gd(III), Fe(III), Mn(III), Y(III), Cr(III), Eu(III), Tb(III), and Dy(III), and X is an optional aliphatic and/or aromatic group; and
a second imaging probe comprising a second targeting moiety that is linked to an enzyme molecule or fragments thereof via a linker region, the second targeting moiety being different than the first targeting moiety and specifically complexing with the second biomarker;
wherein the self-immolative enzyme-activated magnetic resonance contrast agent of the first imaging probe and the enzyme or fragments thereof of the second imaging probe form a signaling complex that produces a detectable signal when the first imaging probe and second imaging probe complex with first and second biomarkers of the cell.

2. The composition of claim 1 , wherein the enzyme is β-galactosidase.

3. The composition of claim 1 , wherein at least one of the first and second biomarkers is extracellular.

4. The composition of claim 1 , wherein at least one of the first and second biomarkers is intracellular.

5. The composition of claim 1 , wherein at least one of the first and second biomarkers is selected from the group consisting of a cellular protease, a kinase, a protein, a cell surface receptor, fatty acid, and lipid.

6. The composition of claim 1 , wherein the first and second biomarkers are cancer cell surface receptors.

7. The composition of claim 1 , wherein the first and second targeting moieties is selected from the group consisting of polypeptides, polynucleotides, lipids, receptor molecules, ligand molecules, aptamers, peptidomimetics, elemental compounds, antibodies, and antibody fragments.

8. The composition of claim 1 , wherein the linker region of the second imaging probe comprises a polymer.

9. The composition of claim 1 , wherein the linker region of the second imaging probe comprises at least one peptide linker.

10. The composition of claim 9 , wherein the at least one peptide linker comprises a biotin-streptavidin-biotin linkage.

Assignees

• Basilion James
• Dhingra Kirti
• Meade Thomas J
• Kamper Sarah Grace
• Univ Case Western Reserve

Inventors

• Basilion James
• Dhingra Kirti
• Meade Thomas J
• Kamper Sarah Grace

Classifications

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G01N33/569

  for microorganisms, e.g. protozoa, bacteria, viruses · CPC title

• A61K49/085 Primary

  conjugated systems · CPC title