Abstract: In one aspect, the present invention provides a contrast enhancement agent comprising an iron chelate having structure I and salts thereof wherein R1 is independently at each occurrence a hydroxy group, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R2-R7 are independently at each occurrence hydrogen, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R1-R7 is a hydroxy group or a C1-C3 hydroxyalkyl group; and wherein Q is one or more charge balancing counterions. Also provided are a metal chelating ligand having structure IX and medical formulations comprising the contrast enhancement agent I.

Abstract: A contrast agent composition and a method of diagnostic imaging are provided. The composition comprises a pharmaceutically acceptable carrier and a metal-complex comprising a ligand having structure (XXX): wherein R1, R2, R3, R7, R8, R?1, R?2, R?3, R7? and R8? are selected form hydrogen, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group; R4, R?4 are selected from a hydrogen, a hydroxyl, a protected hydroxyl group, a protected C1-C3 hydroxyalkyl group, a C1-C3 alkyl group; n is an integer between 0 and 4; R5, R?5 are selected from a hydrogen, a protecting group comprising C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, C2-C30 aromatic radicals, m is an integer between 1 and 10; at least one of R7 and R?7 is acidic groups or protected acidic groups; Y comprises a protein or peptide moiety, a particle, a micelle, a liposome, an organic molecule, oligomer, polymer or a hydrophilic moiety.

Abstract: A chelating agent, a metal-chelate, and a contrast agent are provided, wherein the chelating agent comprises a compound of structure (I) wherein R1, R2, R3, R8, R7, R?7 R?1, R?2, R?3 and R8? are selected from a hydrogen, a protected C1-C3 hydroxyalkyl group, a C1-C3 alkyl group; R4 and R?4 are selected from a hydrogen, a hydroxyl group, a protected hydroxy group, a protected C1-C3 hydroxyalkyl group, a C1-C3 alkyl group; n is an integer between 0 and 4; R5 and R?5 are selected from a hydrogen, a protecting group selected from the group consisting of C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, C2-C30 aromatic radicals; R9 and R?9 are selected form a hydrogen or a protecting group selected from the group consisting of C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, C2-C30 aromatic radicals, m is an integer between 0 and 10; and at least one of R7 and R?7 is acidic group or a protected acidic group.

Abstract: An embodiment of the invention comprises method of imaging a target site comprising administrating ligand of Formula I complexed to 99mTc wherein R1 and R2 are independently an alkyl or cycloalkyl; R3 is and alkyl; X is CO or SO2; Y is (CH2)n, C6H4, (OCH2CH2)n (NHCH2CH2)n and (OCH2CH2CH2)n, or a combination thereof; Z is linker group capable of conjugating to a vector; and n is an integer between 0 and 10.

Abstract: The present teachings provide methods that enable the preparation and purification of radioiodinated vectors without the need for HPLC purification, as well as novel precursors which include biotin-like substituents useful in such methods.

Abstract: An embodiment of the invention comprises a ligand of Formula I wherein R1 and R2 are independently an alkyl or cycloalkyl; R3 is and alkyl; X is CO or SO2; Y is (CH2)n, C6H4, (OCH2CH2)n(NHCH2CH2)n and (OCH2CH2CH2)n, or a combination thereof; Z is linker group capable of conjugating to a vector; and n is an integer between 0 and 10. Also included are an imaging agent comprising a compound of Formula I complexed to 99mTc and their method of use to image a subject having a target site using single photon emission computed tomography (SPECT).

Abstract: Imaging agents are described that comprise labeled substrates capable of being introduced into cells via the cystine/glutamate antiporter. The substrates may be used for imaging or detecting oxidative stress in cells by introducing the labeled agents into cells via the cystine/glutamate antiporter and subsequent detection.

Abstract: In one aspect, the present invention provides a contrast enhancement agent comprising an iron chelate having structure I wherein R1 is independently at each occurrence a hydroxy group, a C1-C3hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R2-R7 are independently at each occurrence hydrogen, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R1-R7 is a hydroxy group or a C1-C3hydroxyalkyl group; and wherein Q is a charge balancing counterion. Also provided is a metal chelating ligand having structure IX and medical formulations comprising the contrast enhancement I.

Abstract: In one aspect, the present invention provides a protected ligand precursor having structure XX wherein R8 is independently at each occurrence a protected hydroxy group, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R9-R11 are independently at each occurrence hydrogen, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R8-R11 is a protected hydroxy group or a protected C1-C3 hydroxyalkyl group; and R12 and R13 are independently at each occurrence a protecting group is selected from the group consisting of C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, and C2-C30 aromatic radicals.

Abstract: The present invention provides novel alpha-fluoroalkyl dihydrotetrabenazine compounds I wherein R1 is a C1-C10 fluorinated aliphatic radical; R2 is hydrogen or a C1-C10 aliphatic radical; R3 is hydrogen or a C1-C10 aliphatic radical; and R4 is a C1-C10 aliphatic radical, a C3-C10 cycloaliphatic radical, or a C3-C10 aromatic radical. The alpha-fluoroalkyl dihydrotetrabenazine compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The alpha-fluoroalkyl dihydrotetrabenazine compounds are believed to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The alpha-fluoroalkyl dihydrotetrabenazine compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled alpha-fluoroalkyl dihydrotetrabenazine compounds are useful as probes for the discovery of PET imaging agents.

Abstract: A method of diagnostic imaging is disclosed comprising administering a medical formulation to a subject, the formulation comprising a contrast enhancement agent having structure I and salts thereof wherein R1 is independently at each occurrence a hydroxy group, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R2-R7 are independently at each occurrence hydrogen, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R1-R7 is a hydroxy group or a C1-C3 hydroxyalkyl group; and wherein Q is one or more charge balancing counterions; and one or more pharmaceutically acceptable carriers and excipients. The subject is subjected to a diagnostic imaging technique such as magnetic resonance imaging. The technique may be used in a variety of diagnostic imaging regimes, such as imaging of circulatory systems, genitourinary systems, hepatobiliary systems, central nervous systems, tumors, and abscesses among others.

Abstract: In one aspect, the present invention provides a contrast enhancement agent comprising an iron chelate having structure I and salts thereof wherein R1 is independently at each occurrence a hydroxy group, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R2-R7 are independently at each occurrence hydrogen, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R1-R7 is a hydroxy group or a C1-C3 hydroxyalkyl group; and wherein Q is one or more charge balancing counterions. Also provided are a metal chelating ligand having structure IX and medical formulations comprising the contrast enhancement agent I.

Abstract: In one aspect, the present invention provides a protected ligand precursor having structure XX wherein R8 is independently at each occurrence a protected hydroxy group, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R9-R11 are independently at each occurrence hydrogen, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R8-R11 is a protected hydroxy group or a protected C1-C3 hydroxyalkyl group; and R12 and R13 are independently at each occurrence a protecting group is selected from the group consisting of C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, and C2-C30 aromatic radicals.

Abstract: The present invention provides novel fluoroalkyl tetrabenazine carbinol compounds having structure I wherein R1 is a C1-C10 fluorinated aliphatic radical; R2 is a C1-C10 aliphatic radical; R3 is hydrogen or a C1-C10 aliphatic radical; R4 is hydrogen or a C1-C10 aliphatic radical; and R5 is hydrogen, a C1-C10 aliphatic radical, a C2-C10 cycloaliphatic radical, or a C2-C20 aromatic radical. In a particular embodiment, —OR5 is an ester moiety. The fluoroalkyl tetrabenazine carbinol compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The fluoroalkyl tetrabenazine carbinol compounds are shown to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The fluoroalkyl tetrabenazine carbinol compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker.

Abstract: A method of preparing a tetrabenazine compound (TBZ compound) having structure I comprising the steps of reacting a nucleophilic alkenyl species with aldehyde compound II and oxidizing the resultant allylic alcohol to provide enone III. The protecting group P1 on the tetrahydroisoquinoline nitrogen is removed and the resultant deprotected intermediate is induced to undergo an amino cyclization reaction to provide a product TBZ compound having structure I. The method may be used to prepare either enantiomeric form of tetrabenazine; (+)-tetrabenazine or (?)-tetrabenazine. Alternatively the method may be adapted to provide a mixture enriched in one tetrabenazine enantiomer, a racemic mixture, or a diastereomeric mixture of tetrabenazine compounds. In addition, the present invention provides novel synthetic intermediate compositions which may be used to prepare either or both enantiomers of tetrabenazine, derivatives of tetrabenazine, and analogs of tetrabenazine.

Abstract: The present invention provides novel fluoroalkyl tetrabenazine carbinol compounds having structure I wherein R1 is a C1-C10 fluorinated aliphatic radical; R2 is a C1-C10 aliphatic radical; R3 is hydrogen or a C1-C10 aliphatic radical; R4 is hydrogen or a C1-C10 aliphatic radical; and R5 is hydrogen, a C1-C10 aliphatic radical, a C2-C10 cycloaliphatic radical, or a C2-C20 aromatic radical. In a particular embodiment, —OR5 is an ester moiety. The fluoroalkyl tetrabenazine carbinol compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The fluoroalkyl tetrabenazine carbinol compounds are shown to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The fluoroalkyl tetrabenazine carbinol compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker.

Abstract: The present invention provides novel fluorophilic compounds having structure VII wherein R1 is a C1-C20 aliphatic, a C2-C20 cycloaliphatic, or a C2-C20 aromatic radical comprising at least one functional group susceptible to reaction with nucleophilic fluoride ion or an electrophilic fluorinating agent; R2 is a C1-C10 aliphatic radical; R3 is hydrogen or a C1-C10 aliphatic radical; R4 is hydrogen or a C1-C10 aliphatic radical; and R5 is hydrogen, a C1-C10 aliphatic radical, a C2-C10 cycloaliphatic radical, or a C2-C20 aromatic radical. The fluorophilic compounds are provided in both racemic and enantiomerically enriched forms and are useful as intermediates in the preparation of novel PET imaging agents and probes useful in the discovery and performance assessment of PET imaging agents.

Abstract: In one aspect, the present invention provides a protected ligand precursor having structure XXI wherein R8 is independently at each occurrence a protected hydroxy group, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R9-R11 are independently at each occurrence hydrogen, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R8-R11 is a protected hydroxy group or a protected C1-C3 hydroxyalkyl group; and R12 and R13 are independently at each occurrence acid sensitive protecting groups.

Abstract: In one aspect, the present invention provides a contrast enhancement agent comprising an iron chelate having structure I wherein R1 is independently at each occurrence a hydroxy group, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R2-R7 are independently at each occurrence hydrogen, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R1-R7 is a hydroxy group or a C1-C3 hydroxyalkyl group; and wherein Q is a charge balancing counterion. Also provided is a metal chelating ligand having structure IX and medical formulations comprising the contrast enhancement I.

Abstract: In one aspect, the present invention provides a protected ligand precursor having structure XX wherein R8 is independently at each occurrence a protected hydroxy group, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R9-R11 are independently at each occurrence hydrogen, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R8-R11 is a protected hydroxy group or a protected C1-C3 hydroxyalkyl group; and R12 and R13 are independently at each occurrence a protecting group is selected from the group consisting of C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, and C2-C30 aromatic radicals.