Radiotracer for positron emission tomography (pet) imaging of alpha1a adrenoceptors in human brain

A method for in vivo imaging of a tissue expressing an α1-AR receptor in a subject, the method comprising:

• administering an effective amount of a radiolabeled compound of Formula (I), or a pharmaceutical salt thereof, to the subject, wherein Formula (I) is
• wherein:
• R1 is a C1-C6 alkyl or a C1-C6 haloalkyl;
• R2 is H, a C1-C6 alkyl, or a C1-C6 haloalkyl;
• or
• R1 and R2 together form a 5- or 6-membered cycloalkyl ring, a substituted or unsubstituted thiophenyl, or a substituted or unsubstituted phenyl;
• R3 is H, a C1-C6 alkyl, a C1-C6 haloalkyl, a C1-C6 hydroxyl alkyl, a C3-C6 cycloalkyl, a C1-C6 alkylnitrile, or an C1-C6 alkylcycloalkyl;
• R4 is C1-C6 alkyl or C1-C6 haloalkyl;
• R5 is H or halide;
• and
• L is a 2 to 10 carbon linking group;
• provided that:
• when R1 is Me, R2 is Me, R3 is H, R4 is —OCH2CF3, and L is —CH2—CH2—CH2—, R5 is not H;
• and
• when R1 is Me, R2 is H, R3 is H, R4 is —OCH2CF3, and L is —CH2—CH2—CH2—, R5 is not H;
• and
• radio-imaging at least a portion of the subject, wherein a position of a radio signal of a resultant radiograph corresponds to a site of the α1-AR receptor in the subject.

A radiolabeled compound of Formula (I)

• or a pharmaceutically acceptable salt thereof,
• wherein:
• R1 is a C1-C6 alkyl or a C1-C6 haloalkyl;
• R2 is H, a C1-C6 alkyl, or a C1-C6 haloalkyl;
• or
• R1 and R2 together form a 5- or 6-membered cycloalkyl ring, a substituted or unsubstituted thiophenyl, or a substituted or unsubstituted phenyl;
• R3 is H, a C1-C6 alkyl, a C1-C6 haloalkyl, a C1-C6 hydroxyl alkyl, a C3-C6 cycloalkyl, a C1-C6 alkylnitrile, or an C1-C6 alkylcycloalkyl;
• R4 is C1-C6 alkyl or C1-C6 haloalkyl;
• R5 is H or halide;
• and
• L is a 2 to 10 carbon linking group;
• provided that:
• when R1 is Me, R2 is Me, R3 is H, R4 is —OCH2CF3, and L is —CH2—CH2—CH2—, R5 is not H;
• and
• when R1 is Me, R2 is H, R3 is H, R4 is —OCH2CF3, and L is —CH2—CH2—CH2—, R5 is not H.