Composition and methods for imaging cells

Patent metadata

Field	Value
Publication number	US-2025099628-A1
Application number	US-202418826492-A
Country	US
Kind code	A1
Filing date	Sep 6, 2024
Priority date	Oct 19, 2009
Publication date	Mar 27, 2025
Grant date	—

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

1 - 32 . (canceled)

33 . A method for imaging a cell having a first biomarker and a second biomarker that is different than the first biomarker, the method comprising the steps of:
contacting the cell with an imaging composition comprising first and second imaging probes, the first imaging probe comprising a first targeting moiety that is linked to an enzyme-activated, contrast agent via a linker region, the first targeting moiety specifically complexing with the first biomarker, the second imaging probe comprising a second targeting moiety that is linked to an activator molecule via a linker region, the second targeting moiety being different from the first targeting moiety and specifically complexing with the second biomarker, the enzyme-activated contrast agent and the activator molecule forming 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; and detecting a signal, the signal being generated when the first imaging probe and second imaging probe complex with first and second biomarkers of the cell.

34 . The method of claim 33 , the cell being contacted with the imaging composition in vivo.

35 . The method of claim 33 , the cell being contacted with the imaging composition ex vivo.

36 . The method of claim 33 , the signal being detected by at least one imaging modality selected from the group consisting of optical, nuclear, and magnetic resonance imaging techniques.

37 . A method for determining a molecular signature of a cell that is associated with disease, the cell having a first biomarker and a second biomarker that is different than the first biomarker, the method comprising the steps of:
contacting the cell with an imaging composition, the imaging composition comprising first and second imaging probes, the first imaging probe comprising a first targeting moiety that is linked to an enzyme-activated, self-immolative contrast agent via a linker region, the first targeting moiety specifically complexing with the first biomarker, the second imaging probe comprising a second targeting moiety that is linked to an activator molecule via a linker region, the second targeting moiety being different than the first targeting moiety and specifically complexing with the second biomarker, the enzyme-activated, self-immolative contrast agent and the activator molecule forming 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; detecting a signal, the signal being generated when the first imaging probe and second imaging probe complex with first and second biomarkers of the cell; and producing the molecular signature of the cell based on the detectable signal, the molecular signature indicating at least one of the type, stage, or severity of the disease.

38 . The method of claim 37 , the cell being contacted with the imaging composition in vivo.

39 . The method of claim 37 , the cell being contacted with the imaging composition ex vivo.

40 . The method of claim 37 , the signal being detected by at least one imaging modality selected from the group consisting of optical, nuclear, and magnetic resonance imaging techniques.

41 . The method of claim 37 , the molecular signature being indicative of a stage of the cell's cell cycle.

42 . The method of claim 37 , the molecular signature being indicative of a type, stage, or severity of cancer.

43 . The method of claim 37 , the molecular signature being indicative of a type, stage, or severity of inflammation.

44 - 56 . (canceled)

57 . The method of claim 37 , wherein the enzyme-activated, self-immolative contrast agent comprises a metal-ion chelator connected to an enzyme substrate via a self-immolative linker, wherein the signaling complex is formed by the cleavage of the self-immolative linker by the activator molecule, and wherein the enzyme-activated, self-immolative contrast agent remains linked to the first targeting moiety via the linker region after cleavage.

58 . The method of claim 37 , wherein the activator molecule comprises β-galactosidase.

59 . The method of claim 33 , wherein the enzyme-activated contrast agent comprises a metal-ion chelator connected to an enzyme substrate via a self-immolative linker, wherein the signaling complex is formed by the cleavage of the self-immolative linker by the activator molecule, and wherein the enzyme-activated contrast agent remains linked to the first targeting moiety via the linker region after cleavage.

60 . The method of claim 33 , wherein the activator molecule comprises β-galactosidase.

61 . The method of claim 33 , further comprising producing a molecular signature of the cell based on the detectable signal, the molecular signature indicating at least one of the type, stage or severity of the disease.

62 . The method of claim 61 , the molecular signature being indicative of a stage of the cell's cell cycle.

63 . The method of claim 61 , the molecular signature being indicative of a type, stage, or severity of cancer.

64 . The method of claim 61 , the molecular signature being indicative of a type, stage, or severity of inflammation.

65 . The method of claim 33 , wherein the enzyme-activated contrast agent is selected from the group consisting of o-nitrophenyl-b-D-galactopyranoside (ONPG) or its para analog (i.e., PNPG), GB137, and 1-(2-(β-Galactopyranosyloxy) propyl)-4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) gadolinium (III) (EGadMe

Assignees

• Univ Case Western Reserve
• Univ Northwestern

Inventors

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

Classifications

• A61K49/085 Primary

  conjugated systems · CPC title

• A61K49/0017

  Fluorescence in vivo · CPC title

• A61K49/14

  Peptides, e.g. proteins · CPC title

• A61K49/0002

  General or multifunctional contrast agents, e.g. chelated agents · CPC title

• A61K49/10

  Organic compounds · CPC title