Curcumin derivatives for amyloid-beta plaque imaging
AssigneeMassachusetts General Hospital
InventorsRan Chongzhao, Anna Moore
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Abstract
The present invention provides curcumin-derived near infrared (NIR) imaging probes. Upon interacting with amyloid β aggregates, these probes undergo a range of changes, qualifying them as “smart” probes. The inventors have demonstrated that probes of the invention have the capacity to monitor the progression of Alzheimer's disease in an in vivo animal model. In addition, the present invention encompasses probes useful as PET imaging agents, MRI imaging agents and multimodal imaging agents, as well as related methods of detecting and imaging amyloid β aggregates and plaques.
Claims20
A method for detecting an amyloid beta plaque in a sample, comprising:
- (a) contacting a sample comprising an amyloid beta plaque with a compound, such that said compound binds the amyloid beta plaque, wherein the compound having the formula Ar1-L-Ar2 and wherein:
- (i) L is a divalent linking group comprising an alkenylene having 5 to 15 backbone carbon atoms, wherein at least two of the backbone carbon atoms form part of a carbonyl or secondary alcohol and Ar1 and Ar2 are each independently alkyl amine-substituted aryl or heteroaryl groups;
- or
- (ii) L is a divalent linking group comprising an alkenylene having 5 to 15 backbone carbon atoms, wherein at least two of the backbone carbon atoms form part of a difluoroboronate ring;
- and Ar1 and Ar2 are each independently alkyl amine-substituted aryl or heteroaryl groups;
- (b) illuminating said compound bound to the amyloid beta plaque with near infrared light of a wavelength absorbable by said compound;
- and
- (c) detecting fluorescence emitted by the compound wherein said fluorescence corresponds to the amyloid beta plaque contained in said sample.
An in vivo optical imaging method for amyloid beta plaque detection, comprising:
- (a) administering to a subject a compound, wherein said compound binds an amyloid beta plaque, wherein the compound having the formula Ar1-L-Ar2 and wherein:
- (i) L is a divalent linking group comprising an alkenylene having 5 to 15 backbone carbon atoms, wherein at least two of the backbone carbon atoms form part of a carbonyl or secondary alcohol and Ar1 and Ar2 are each independently alkyl amine-substituted aryl or heteroaryl groups;
- or
- (ii) L is a divalent linking group comprising an alkenylene having 5 to 15 backbone carbon atoms, wherein at least two of the backbone carbon atoms form part of a difluoroboronate ring;
- and Ar1 and Ar2 are each independently alkyl amine-substituted aryl or heteroaryl groups;
- (b) illuminating the subject with near infrared light of a wavelength absorbable by said compound;
- and
- (c) detecting fluorescence emitted by the compound wherein said fluorescence corresponds to the amyloid beta plaque present in the subject.
A method for providing a positron emission tomography (PET) scan of a subject, comprising:
- (a) administering to a subject a 11C or 18F labeled derivative of a compound, wherein the compound having the formula Ar1-L-Ar2 and wherein:
- (i) L is a divalent linking group comprising an alkenylene having 5 to 15 backbone carbon atoms, wherein at least two of the backbone carbon atoms form part of a carbonyl or secondary alcohol and Ar1 and Ar2 are each independently alkyl amine-substituted aryl or heteroaryl groups;
- or
- (ii) L is a divalent linking group comprising an alkenylene having 5 to 15 backbone carbon atoms, wherein at least two of the backbone carbon atoms form part of a difluoroboronate ring;
- and Ar1 and Ar2 are each independently alkyl amine-substituted aryl or heteroaryl groups;
- and
- (b) imaging gamma rays emitted due to the compound within said subject in order to provide a PET scan of the compound contained in said subject.
A method for providing a magnetic resonance image of a subject, comprising:
- (a) administering to a subject a 19F labeled derivative of a compound, wherein the compound having the formula Ar1-L-Ar2 and wherein:
- (i) L is a divalent linking group comprising an alkenylene having 5 to 15 backbone carbon atoms, wherein at least two of the backbone carbon atoms form part of a carbonyl or secondary alcohol and Ar1 and Ar2 are each independently alkyl amine-substituted aryl or heteroaryl groups;
- or
- (ii) L is a divalent linking group comprising an alkenylene having 5 to 15 backbone carbon atoms, wherein at least two of the backbone carbon atoms form part of a difluoroboronate ring;
- and Ar1 and Ar2 are each independently alkyl amine-substituted aryl or heteroaryl groups;
- and
- (b) imaging the subject in order to obtain a magnetic resonance image of the compound contained within the subject.
Dependencies are inferred from the claim text.