General Electric Company

Other

Bechtel Bwxt Idaho, Lcc

Centre for Probe Development and Commercialization

Bruce Fletcher Johnson

Grigorii Lev Soloveichik

Kirill Vladimirovich Shalyaev

Donald Wayne Whisenhunt, Jr

Eric James Pressman

Michael James Rishel

James Lawrence Spivack

James Norman Cawse

Sean Richard Dinn

Kande Kankanamalage Dayarathna Amarasinghe

John Yaw Ofori

Mohan Mark Amaratunga

Marsha Mottel Grade

Randall Lee Carter

Tao Wu

Tiberiu Mircea Siclovan

Frank John Mondello

John Fitzmaurice Valliant

Cristina Abucay Tan Hehir

John Henry Lobos

Donald Herbert Maylotte

Cheryl Lynn Sabourin

Karin Ann Stephenson

Yang Yang

Donald Wayne Whisenhunt

Kande Kankananamalage Dayarathna Amarasinghe

Anup Sood

Victoria Eugenia Cotero

Rong Zhang

Ileana Hancu

Faisal Ahmed Syud

Jack Mathew Webster

Richard Anthony Battista

Brian Duh-Lan Lee

Thomas E Ward

Paritosh Jayant Dhawale

Chittari Pabba

Johan Ulin

Eric Douglas Williams

Kenneth Michael Fish

Phillip Oscar Moreno

Nicole Evelyn Barnhardt

Nadeem Ishaque

Amy Casey Williams

Denyce Kramer Wicht

Deborah K Bulmer

Carolyn S Watkins

Maxim Y Kiselev

Mark Christopher Patrick Darey

Mark Christopher Darey

An embodiment of the invention comprises method of imaging a target site comprising administrating ligand of Formula I complexed toTc wherein Rand Rare independently an alkyl or cycloalkyl; Ris and alkyl; X is CO or SO; Y is (CH2), CH, (OCHCH)(NHCHCH)and (OCHCHCH), or a combination thereof; Z is linker group capable of conjugating to a vector; and n is an integer between 0 and 10.

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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.

Biotin stannane for HPLC-free radioiodination

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.

Labeled molecular imaging agents and methods of use

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.

Agents and methods for the imaging of myelin basic protein

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.

Imaging of myelin basic protein

The present invention provides novel alpha-fluoroalkyl dihydrotetrabenazine compounds I wherein Ris a C-Cfluorinated aliphatic radical; Ris hydrogen or a C-Caliphatic radical; Ris hydrogen or a C-Caliphatic radical; and Ris a C-Caliphatic radical, a C-Ccycloaliphatic radical, or a C-Caromatic 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.

Alpha-fluoroalkyl dihydrotetrabenazine imaging agents and probes

The present invention provides novel fluoroalkyl tetrabenazine carbinol compounds having structure I wherein Ris a C-Cfluorinated aliphatic radical; Ris a C-Caliphatic radical; Ris hydrogen or a C-Caliphatic radical; Ris hydrogen or a C-Caliphatic radical; and Ris hydrogen, a C-Caliphatic radical, a C-Ccycloaliphatic radical, or a C-Caromatic radical. In a particular embodiment, &#x2014;ORis 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. The non-radiolabled fluoroalkyl tetrabenazine carbinol compounds are useful as probes for the discovery of PET imaging agents.

Fluoroalkyl tetrabenazine carbinol compounds as imaging agents and probes

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 Pon 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 (&#x2212;)-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.

Intermediates useful for making tetrabenazine compounds

The present invention provides novel fluorophilic compounds having structure VII wherein Ris a C-Caliphatic, a C-Ccycloaliphatic, or a C-Caromatic radical comprising at least one functional group susceptible to reaction with nucleophilic fluoride ion or an electrophilic fluorinating agent; Ris a C-Caliphatic radical; Ris hydrogen or a C-Caliphatic radical; Ris hydrogen or a C-Caliphatic radical; and Ris hydrogen, a C-Caliphatic radical, a C-Ccycloaliphatic radical, or a C-Caromatic 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.

Intermediates for fluorinated tetrabenazine carbinol compounds imaging agents and probes

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; Ris a C-Caliphatic, C-Ccycloaliphatic, or C-Caromatic radical comprising at least one functional group susceptible to reaction with nucleophilic fluoride ion or an electrophilic fluorinating agent; Ris hydrogen or a C-Caliphatic radical; and Ris hydrogen or a C-Caliphatic 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.

Intermediates for alpha-fluoroalkyl tetrabenazine and dihydrotetrabenazine imaging agents and probes

The present invention provides novel alpha-fluoroalkyl compounds having structure I and the corresponding dihydrotetrabenazine compounds IV wherein Ris a C-Cfluorinated aliphatic radical; Ris hydrogen or a C-Caliphatic radical; and Ris hydrogen or a C-Caliphatic 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.

Alpha-fluoroalkyl tetrabenazine and dihydrotetrabenazine imaging agents and probes

The present invention provides novel fluorinated ether compounds having structure I wherein Ris a C-Cfluorinated aliphatic radical; Ris a C-Caliphatic radical, or a C-Ccycloaliphatic radical; Ris hydrogen or a C-Caliphatic radical; and Ris hydrogen or a C-Caliphatic 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.

Fluorinated dihydrotetrabenazine ether imaging agents and probes

The present invention provides novel fluorophilic compounds having structure VI wherein Ris a C-Caliphatic, a C-Ccycloaliphatic, or a C-Caromatic radical comprising at least one functional group susceptible to reaction with nucleophilic fluoride ion or an electrophilic fluorinating agent; Ris a C-Caliphatic radical, or a C-Ccycloaliphatic radical; Ris hydrogen or a C-Caliphatic radical; and Ris hydrogen or a C-Caliphatic 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.

Intermediates for fluorinated dihydrotetrabenazine ether imaging agents and probes

Method for making tetrabenazine compounds

This invention relates to bifunctional detection agents useful for providing high-resolution, in vivo imaging of biochemical activity in a living organism. Methods of using these bifunctional detection agents may comprise administering them into a living organism, and then estimating the localization of the detection agent using one modality (i.e., MRI), while concurrently estimating the level of biological activity using a second modality (i.e., optical imaging). One of the bifunctional detection agents comprises a magnetic resonance component and an optical imaging component. The magnetic resonance component comprises a contrast agent that is always activated or 'on'. The optical imaging component comprises an activatable contrast agent or dye that is activated or turned 'on' only in the presence of a particular event. For example, the optical imaging component may be activated by a certain wavelength of light and (1) by the presence of a particular biochemical marker, (2) by enzyme cleavage, or (3) by a change in the temperature or pH of the surrounding medium. These bifunctional detection agents allow both anatomical and functional/metabolic information to be obtained simultaneously.

Systems and methods for high-resolution in vivo imaging of biochemical activity in a living organism

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Scotia, NY, United States of America

Bruce Fletcher Johnson