Heterocyclic compounds and imaging agents for imaging huntingtin protein
Provided herein are certain compounds and imaging agents useful for detecting a disease or condition associated with protein aggregation, compositions thereof, and methods of their use.
1. A compound of formula:
or an isotopically enriched analog, pharmaceutically acceptable salt, tautomer, stereoisomer, or a mixture of stereoisomers thereof, wherein the compound is labeled with one or more positron-emitting radioactive isotopes selected from 11 C, 13 N, 15 O, and 18 F.
2. A method of generating diagnostic images in an individual comprising administering an effective amount of a compound of claim 1 to an individual, and generating an image of a body part or body area of the individual.
3. The method of claim 2 , wherein generating an image of a body part or body area of the individual comprises generating an image to detect the presence or absence of a protein susceptible to aggregation in the image.
4. The method of claim 3 , wherein the protein susceptible to aggregation is huntingtin protein (HTT protein).
5. The method of claim 3 , wherein the presence or absence of a protein aggregate corresponds to the presence or absence of a neurodegenerative disease.
6. The method of claim 5 , wherein the neurodegenerative disease is selected from Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, Prion disease and spinocerebellar ataxias.
7. The method of claim 6 , wherein the neurodegenerative disease is Huntington's disease (HD).
8. The method of claim 2 , wherein generating an image comprises positron emission tomography (PET) imaging, PET with concurrent computed tomography imaging (PET/CT), PET with concurrent magnetic resonance imaging (PET/MRI), single-photon emission computed tomography (SPECT) imaging, or a combination thereof.