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US 12,083,191 B2Granted
Composition and methods for imaging cells
AssigneesCase Western Reserve University, Northwestern University
InventorsJames Basilion, Kirti Dhingra, Thomas J. Meade, Sarah Grace Kamper
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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.
Claims12
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) a first imaging probe comprising:
- a first targeting moiety, an enzyme-activated contrast agent having an enzyme substrate, and a first linker region,
- wherein the first linker region links the enzyme-activated contrast agent to the first targeting moiety,
- wherein the enzyme-activated contrast agent is 1-(2-(β-Galactopyranosyloxy)propyl)-4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) gadolinium(III) (EGadMe), and
- wherein the first targeting moiety specifically complexes with the first biomarker;
- and
- (b) a second imaging probe comprising:
- a second targeting moiety, an activator molecule comprising β-galactosidase or fragments thereof, and a second linker region,
- wherein the second linker region links the activator molecule to the second targeting moiety,
- wherein the β-galactosidase or fragments thereof of the activator molecule activates the enzyme-activated contrast agent by enzymatic cleavage of the enzyme substrate of the enzyme-activated contrast agent,
- wherein the second targeting moiety is different than the first targeting moiety and specifically complexes with the second biomarker, and
- wherein the composition produces a detectable signal when the first targeting moiety of the first imaging probe and the second targeting moiety of the second imaging probe complex with first and second biomarkers of the cell to bring the first imaging probe and the second imaging probe in proximity to each other so that the enzyme substrate of the enzyme-activated contrast agent of the first imaging probe is cleaved by the β-galactosidase or fragments thereof of the second imaging probe to produce the detectable signal;
- and
- wherein the enzyme-activated contrast agent remains linked to the first targeting moiety via the first linker region after activation by the β-galactosidase or fragments thereof of the second imaging probe.
11 more elements
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) a first imaging probe comprising:
- a first targeting moiety, an self-immolative enzyme-activated contrast agent having an enzyme substrate, and a first linker region,
- wherein the first linker region links the self-immolative enzyme-activated contrast agent to the first targeting moiety,
- wherein the self-immolative enzyme-activated contrast agent is 1-(2-(β-Galactopyranosyloxy)propyl)-4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) gadolinium(III) (EGadMe), and
- wherein the first targeting moiety specifically complexing with the first biomarker;
- and
- (b) a second imaging probe comprising:
- a second targeting moiety, an activator molecule comprising β-galactosidase or fragments thereof, and a second linker region,
- wherein the second linker region links the activator molecule to the second targeting moiety,
- wherein the β-galactosidase or fragments thereof of the activator molecule activates the self-immolative enzyme-activated contrast agent by enzymatic cleavage of the enzyme substrate of the self-immolative enzyme-activated contrast agent, and
- wherein the second targeting moiety is different than the first targeting moiety and specifically complexes with the second biomarker;
- wherein the composition produces a detectable signal when the first targeting moiety of the first imaging probe and the second targeting moiety of the second imaging probe complex with first and second biomarkers of the cell to bring the first imaging probe and the second imaging probe in proximity to each other so that the enzyme substrate of the self-immolative enzyme activated contrast agent of the first imaging probe is cleaved by the β-galactosidase or fragments thereof of the second imaging probe to produce the detectable signal,
- wherein at least one of the first and second linker regions comprising a biotin-streptavidin-biotin linkage, and
- wherein the self-immolative enzyme-activated contrast agent remains linked to the first targeting moiety via the first linker region after activation by the enzyme or fragments thereof of the second imaging probe.
11 more elements
Dependencies are inferred from the claim text.