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: 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: 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 invention relates to agents capable of binding to myelin basic protein in a subject. Also provided are methods for the detection of myelin-associated neuropathy comprising identifying a subject at risk of or diagnosed with a myelin-associated neuropathy, administering to a subject an agent that binds specifically to myelin basic protein, and determining myelination in the subject by detecting the agent present in the subject. A kit containing the agent or its derivatives for use in detecting myelin basic protein is also provided.

Abstract: The present invention relates to methods for myelin basic protein detection comprises identifying a subject at risk of or diagnosed with a myelin-associated neuropathy, parenterally administering to the subject the agent, and determining myelination in the subject by detecting binding to myelin basic protein. Methods for the detection of myelin and a quantitative measurement of its local concentration in a sample using an agent with specific binding to myelin basic protein are also provided as is a kit containing the agent or its derivatives for use in detecting myelin basic protein.

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: 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: 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 relates to agents capable of binding to myelin basic protein in a subject. Also provided are methods for the detection of myelin-associated neuropathy comprising identifying a subject at risk of or diagnosed with a myelin-associated neuropathy, administering to a subject an agent that binds specifically to myelin basic protein, and determining myelination in the subject by detecting the agent present in the subject. A kit containing the agent or its derivatives for use in detecting myelin basic protein is also provided.

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: The present invention provides novel fluorophilic compounds having structure VII wherein Q is a carbonyl group, a protected carbonyl group, a hydroxy methine group, or a protected hydroxy methine group; R1 is a C1-C20 aliphatic, C2-C20 cycloaliphatic, or C2-C20 aromatic radical comprising at least one functional group susceptible to reaction with nucleophilic fluoride ion or an electrophilic fluorinating agent; R2 is hydrogen or a C1-C10 aliphatic radical; and R3 is hydrogen or a C1-C10 aliphatic 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. The fluorophilic compounds are particularly useful in the preparation of PET imaging agents and probes having a high affinity for VMAT-2, a biomarker implicated in human diabetes and other illnesses such as Parkinson's disease.

Abstract: The present invention provides novel alpha-fluoroalkyl compounds having structure I and the corresponding dihydrotetrabenazine compounds IV wherein R1 is a C1-C10 fluorinated aliphatic radical; R2 is hydrogen or a C1-C10 aliphatic radical; and R3 is hydrogen or a C1-C10 aliphatic radical. The alpha-fluoroalkyl 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 compounds are shown to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The alpha-fluoroalkyl compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled alpha-fluoroalkyl compounds are useful as probes for the discovery of PET imaging agents.

Abstract: The present invention provides novel fluorophilic compounds having structure VI wherein R1 is a C2-C20 aliphatic, a C3-C20 cycloaliphatic, or a C3-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, or a C3-C10 cycloaliphatic radical; R3 is hydrogen or a C1-C10 aliphatic radical; and R4 is hydrogen or a C1-C10 aliphatic 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. The fluorophilic compounds are particularly useful in the preparation of PET imaging agents and probes having a high affinity for VMAT-2, a biomarker implicated in human diabetes and other illnesses such as Parkinson's disease.

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 fluorinated ether compounds having structure I wherein R1 is a C2-C10 fluorinated aliphatic radical; R2 is a C1-C10 aliphatic radical, or a C3-C10 cycloaliphatic radical; R3 is hydrogen or a C1-C10 aliphatic radical; and R4 is hydrogen or a C1-C10 aliphatic radical. The fluorinated ether compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The fluorinated ether compounds are shown to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The fluorinated ether compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabeled fluorinated ether compounds are useful as probes for the discovery of PET imaging agents.