DERIVATIVES OF DIBENZOTHIOPHENE IMAGING OF alpha-7 NICOTINIC ACETYLCHOLINE RECEPTORS
AssigneeThe Johns Hopkins University
InventorsYongjun Gao, Andrew Horti, Robert Dannals, Richard Wahl, Ronnie Mease, Ken Kellar, Paige Finley, Martin Pomper
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Abstract
The presently disclosed subject matter provides non-invasive methods for imaging, quantifying α7 nicotinic cholinergic receptors, and diagnosing a disease or condition associated with α7-nAChRs. Methods for preparing radiolabeled derivatives of dibenzothiophene and compounds provided thereof also are provided.
Claims37
A non-invasive method for imaging one or more α7-nicotinic acetylcholine receptors (α7-nAChRs) in the brain of a subject, the method comprising:
- administering to the subject an effective amount of a radiolabeled compound of Formula (I)
- or a pharmaceutically acceptable salt, hydrate or prodrug thereof;
- allowing the radiolabeled compound to bind to the α7-nAChRs in the brain of the subject;
- and
- obtaining an image of the α7-nAChRs in the brain of the subject.
A non-invasive method for quantifying one or more α7-nicotinic acetylcholine receptors (α7-nAChRs) in the brain of a subject, the method comprising:
- administering to the subject an effective amount of a radiolabeled compound of Formula (I)
- or a pharmaceutically acceptable salt, hydrate or prodrug thereof;
- allowing the radiolabeled compound to bind to the one or more α7-nAChRs in the brain of the subject;
- obtaining an image of the brain of the subject showing the distribution of the radiolabeled compound;
- and
- deriving a standardized uptake value (SUV) from the image of the brain.
A non-invasive method for imaging one or more α7-nicotinic acetylcholine receptors (α7-nAChRs) in the brain of a subject, the method comprising:
- administering to the subject an effective amount of [18F]-ASEM compound, or a pharmaceutically acceptable salt, hydrate or prodrug thereof;
- allowing the compound to bind to the one or more α7-nAChRs in the brain of the subject;
- and
- obtaining an image of the brain of the subject using positron emission tomography, wherein the binding is reversible.
A non-invasive method for quantifying one or more α7-nicotinic acetylcholine receptors (α7-nAChRs) in the brain of a subject, the method comprising:
- administering to the subject an effective amount of [18F]-ASEM compound, or a pharmaceutically acceptable salt, hydrate or prodrug thereof;
- allowing the compound to bind to the one or more α7-nAChRs in the brain of the subject;
- obtaining a positron emission tomography (PET) image of the brain of the subject showing the distribution of the compound;
- and
- deriving a standardized uptake value (SUV) from the image of the brain.
A non-invasive method for diagnosing a disease or condition associated with α7-nAChRs in a subject in need thereof, the method comprising:
- administering to the subject a composition comprising an effective amount of a radiolabeled compound of Formula (I), (II) or (III):
- or a pharmaceutically acceptable salt, hydrate or prodrug thereof,
- allowing the radiolabeled compound to bind to the α7-nAChRs in the brain of the subject;
- and
- obtaining an imaging of the brain of the subject,
- wherein an alteration in the density of α7-nAChRs in the brain as compared to the brain of a subject without the disease or condition is indicative that the subject has the disease or condition associated with α7-nAChRs.
A method for preparing a compound of Formula (I):
- the method comprising:
- (a) contacting a solution of a compound of Formula (IV)
- in a solvent with Na 125I to form a mixture;
- (b) adding an acid to the mixture;
- (c) heating the mixture;
- (d) cooling the mixture;
- (e) diluting the mixture in an appropriate solvent;
- (f) applying the diluted mixture to a reverse phase HPLC column;
- (g) collecting the radioactive peak;
- (h) transferring the radioactive peak to a solid phase extraction (SPE) cartridge;
- (i) eluting the product through a filter;
- and
- (j) adding saline and a solution of sodium bicarbonate through the filter to form Formula (I).
A compound of Formula (I):
- or a pharmaceutically acceptable salt, hydrate or prodrug thereof.
Dependencies are inferred from the claim text.