Compositions, methods, and systems for the synthesis and use of imaging agents

A method of determining perfusion and innervation mismatch in a portion of a human subject, comprising:

• administering to the subject a first imaging agent and acquiring at least one first image of a portion of the subject, wherein the first imaging agent is employed to image perfusion;
• administering to the subject a second imaging agent and acquiring at least one second image of the portion of the subject, wherein the second imaging agent is employed to image innervation;
• and
• determining regional mismatch of innervation and perfusion areas in the portion of the subject based at least in part on the at least one first image and the at least one second image, wherein the first imaging agent has the structure:
• wherein
• J is selected from the group consisting of N(R28), S, O, C(═O), C(═O)O, NHCH2CH2O, a bond, and C(═O)N(R27);
• when present, K is selected from the group consisting of hydrogen, alkoxyalkyl optionally substituted with an imaging moiety, alkyloxy optionally substituted with an imaging moiety, aryl optionally substituted with an imaging moiety, C1-C6 alkyl optionally substituted with an imaging moiety, heteroaryl optionally substituted with an imaging moiety, and an imaging moiety;
• when present, L is selected from the group consisting of hydrogen, alkoxyalkyl optionally substituted with an imaging moiety, alkyloxy optionally substituted with an imaging moiety, aryl optionally substituted with an imaging moiety, C1-C6 alkyl optionally substituted with an imaging moiety, heteroaryl optionally substituted with an imaging moiety, and an imaging moiety;
• M is selected from the group consisting of hydrogen, alkoxyalkyl optionally substituted with an imaging moiety, alkyloxy optionally substituted with an imaging moiety, aryl optionally substituted with an imaging moiety, C1-C6 alkyl optionally substituted with an imaging moiety, heteroaryl optionally substituted with an imaging moiety, and an imaging moiety;
• or
• L and M, together with the atom to which they are attached, may form a three- or four-membered carbocyclic ring;
• Q is halo or haloalkyl;
• n is 0, 1, 2, or 3;
• R21, R22, R27, and R28 are independently selected from hydrogen, C1-C6 alkyl optionally substituted with an imaging moiety, and an imaging moiety;
• R23, R24, R25, and R26 are independently selected from hydrogen, halogen, hydroxyl, alkyloxy, C1-C6 alkyl optionally substituted with an imaging moiety, and an imaging moiety;
• R29 is C1-C6 alkyl optionally substituted with an imaging moiety;
• and Y
• is selected from the group consisting of a bond, carbon, and oxygen;
• provided that when Y is a bond, K and L are absent, and M is selected from the group consisting of aryl optionally substituted with an imaging moiety and heteroaryl optionally substituted with an imaging moiety;
• and provided that when Y is oxygen, K and L are absent, and M is selected from hydrogen, alkoxyalkyl optionally substituted with an imaging moiety, aryl optionally substituted with an imaging moiety, C1-C6 alkyl optionally substituted with an imaging moiety, and heteroaryl optionally substituted with an imaging moiety;
• provided that at least one imaging moiety is present,
• or a salt thereof.