Novel compounds that find use as imaging agents within nuclear medicine applications (PET imaging) for imaging of cardiac innervation are disclosed. These PET based radiotracers may exhibit increased stability, decreased NE release (thereby reducing side effects), improved quantitative data, and/or high affinity for VMAT over prior radiotracers. Methods of using the compounds to image cardiac innervation are also provided. In some instances the compounds are developed by derivatizing certain compounds with 18F in a variety of positions: aryl, alkyl, a keto, benzylic, beta-alkylethers, gamma-propylalkylethers and beta-proplylalkylethers. Alternatively or additionally, a methyl group a is added to the amine, and/or the catechol functionality is either eliminated or masked as a way of making these compounds more stable.

Novel compounds that find use as imaging agents within nuclear medicine applications (PET imaging) for imaging of cardiac innervation are disclosed. These PET based radiotracers may exhibit increased stability, decreased NE release (thereby reducing side effects), improved quantitative data, and/or high affinity for VMAT over prior radiotracers. Methods of using the compounds to image cardiac innervation are also provided. In some instances the compounds are developed by derivatizing certain compounds with 18F in a variety of positions: aryl, alkyl, a keto, benzylic, beta-alkylethers, gamma-propylalkylethers and beta-proplylalkylethers. Alternatively or additionally, a methyl group a is added to the amine, and/or the catechol functionality is either eliminated or masked as a way of making these compounds more stable.

The present invention relates to systems, compositions, and methods for the synthesis and use of imaging agents, or precursors thereof. An imaging agent precursor may be converted to an imaging agent using the methods described herein. In some cases, the imaging agent is enriched in .sup.18F. In some cases, an imaging agent may be used to image an area of interest in a subject, including, but not limited to, the heart, cardiovascular system, cardiac vessels, brain, and other organs. In some embodiments, methods and compositions for assessing perfusion and innervation mismatch in a portion of a subject are provided.

The present invention relates to systems, compositions, and methods for the synthesis and use of imaging agents, or precursors thereof. An imaging agent precursor may be converted to an imaging agent using the methods described herein. In some cases, the imaging agent is enriched in .sup.18F. In some cases, an imaging agent may be used to image an area of interest in a subject, including, but not limited to, the heart, cardiovascular system, cardiac vessels, brain, and other organs. In some embodiments, methods and compositions for assessing perfusion and innervation mismatch in a portion of a subject are provided.

A method of imaging, the method comprising administering, to a subject, a compound of Structure Alpha, of the formula: ##STR00001## or a pharmaceutically acceptable salt thereof, wherein: n is 0; R, R.sub.1, and R.sub.3 are independently selected from the group consisting of H, OR.sub.4, F, Cl, Br, I, CF.sub.3, alkyl (C.sub.1-C.sub.4), aryl, heteroaryl, C(O)R.sub.4, CO.sub.2R.sub.4, N(R.sub.4).sub.2, CN, C(NR.sub.4)OR.sub.5, NR.sub.4C(NR.sub.5)NHR.sub.6, C(NR.sub.4)NHR.sub.5, C(O)NHR.sub.4, NR.sub.4C(O)NR.sub.5, NR.sub.4NR.sub.5, SO.sub.2OR.sub.4, and imaging moiety Im; R.sub.2 is absent; R.sub.4, R.sub.5, and R.sub.6 are independently selected from the group consisting of H, alkyl, aryl and heteroaryl substituents; wherein the alkyl, aryl, or heteroaryl may be substituted with imaging moiety Im, wherein optionally any two of R.sub.4, R.sub.5, and R.sub.6 form a cyclic structure selected from the group consisting of CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2, CHCH, XCH, and XCHCH, wherein X is selected from the group consisting of O, NH, and NR.sub.7, and wherein R.sub.7 is selected from the group consisting of alkyl, aryl, and heteroaryl substituents; W, X, Y and Z are independently selected from the group consisting of H, OR.sub.4, N(R.sub.4).sub.2, F, Cl, Br, I, CF.sub.3, imaging moiety Im, aryl, and heteroaryl; A is O or absent; and imaging moiety Im is .sup.18F, .sup.76Br, .sup.124I, .sup.131I, .sup.99mTc, .sup.153Gd, or .sup.111In; and acquiring at least one image of the subject.

A method of imaging, the method comprising administering, to a subject, a compound of Structure Alpha, of the formula: ##STR00001## or a pharmaceutically acceptable salt thereof, wherein: n is 0; R, R.sub.1, and R.sub.3 are independently selected from the group consisting of H, OR.sub.4, F, Cl, Br, I, CF.sub.3, alkyl (C.sub.1-C.sub.4), aryl, heteroaryl, C(O)R.sub.4, CO.sub.2R.sub.4, N(R.sub.4).sub.2, CN, C(NR.sub.4)OR.sub.5, NR.sub.4C(NR.sub.5)NHR.sub.6, C(NR.sub.4)NHR.sub.5, C(O)NHR.sub.4, NR.sub.4C(O)NR.sub.5, NR.sub.4NR.sub.5, SO.sub.2OR.sub.4, and imaging moiety Im; R.sub.2 is absent; R.sub.4, R.sub.5, and R.sub.6 are independently selected from the group consisting of H, alkyl, aryl and heteroaryl substituents; wherein the alkyl, aryl, or heteroaryl may be substituted with imaging moiety Im, wherein optionally any two of R.sub.4, R.sub.5, and R.sub.6 form a cyclic structure selected from the group consisting of CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2, CHCH, XCH, and XCHCH, wherein X is selected from the group consisting of O, NH, and NR.sub.7, and wherein R.sub.7 is selected from the group consisting of alkyl, aryl, and heteroaryl substituents; W, X, Y and Z are independently selected from the group consisting of H, OR.sub.4, N(R.sub.4).sub.2, F, Cl, Br, I, CF.sub.3, imaging moiety Im, aryl, and heteroaryl; A is O or absent; and imaging moiety Im is .sup.18F, .sup.76Br, .sup.124I, .sup.131I, .sup.99mTc, .sup.153Gd, or .sup.111In; and acquiring at least one image of the subject.

Provided herein are compounds of Formula (I), or pharmaceutically acceptable salt thereof, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, and n are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) or pharmaceutically acceptable salt thereof, and methods of using a compound of Formula (I) or pharmaceutically acceptable salt thereof, e.g., in the treatment of a mental health disease or disorder. ##STR00001##