General Electric Company

Ge Healthcare As

Other

Arizona State University

Global Life Sciences Solutions USA LLC

Centre for Probe Development and Commercialization

Michael James Rishel

Bruce Fletcher Johnson

Sean Richard Dinn

Kande Kankanamalage Dayarathna Amarasinghe

Brian James Grimmond

Rong Zhang

Brian Christopher Bales

Tao Wu

Anup Sood

Mikkel Jacob Thaning

Andreas Richard Meijer

Randall Lee Carter

John Fitzmaurice Valliant

Jeannette Christine Roberts

Karin Ann Stephenson

Jeannette Christine DePuy

Yang Yang

Kande Kankananamalage Dayarathna Amarasinghe

John Richard Nelson

Sidney M Hecht

Arunkumar Natarajan

Uwe Wiedmann

Michael John Gerdes

Chad Allan Smith

Ross Christopher Stalter

Wei Gao

Robert Scott Duthie

Ryan Charles Heller

Jack Mathew Webster

Nichole Lea Wood

Brian Duh-Lan Lee

Michael Todd Luttrell

Chittari Pabba

Rakesh Paul

Manikandadas Mathilakathu Madathil

Paul Francis Fitzgerald

Chandrabali Bhattacharya

Mary Elizabeth Spilker

Trevor Bozeman

Klaus Gustav Hentrich

Mark Christopher Patrick Darey

Zhiqiang Yu

Stephen Lorenco Araujo

Mark Christopher Darey

Sean R Dinn

Jeannette Christine Depuy

A method is provided for generating single-stranded DNA circles from a biological sample. The method comprises the steps of: treating the biological sample with an extractant to release nucleic acids, thereby forming a sample mixture; neutralizing the extractant; denaturing the released nucleic acids to generate single-stranded nucleic acids; and contacting the single-stranded nucleic acids with a ligase that is capable of template-independent, intramolecular ligation of single-stranded DNA to generate the single-stranded DNA circles. All the steps of the method are performed without any intermediate nucleic acid isolation or nucleic acid purification. The single-stranded DNA circles may be amplified and further analyzed. Also provided is a kit which comprises compositions for carrying out the novel methods.

Method for nucleic acid analysis directly from an unpurified biological sample

The invention provides compounds suitable for use as contrast agents in magnetic resonance imaging (MRI). The compounds of the present invention are manganese (II) complexes having advantageous properties as compared with similar known compounds.

Chelate compounds

Anionic chelate compounds

Manganese chelate compounds

This invention relates to compounds comprising a saccharide conjugated to an imaging agent or a reporter group, compositions comprising them and methods of using them. Specifically BLM-disaccharide and BLM-monosaccharide conjugates containing different linker groups and an imaging agent or a reporter group are provided for the targeting and imaging of tumors.

Saccharide conjugates

Disclosed are high throughput methods of probing multiple targets in a biological sample where the recurrent time-consuming antibody incubation steps and individual signal modification and activation steps are replaced by simultaneous hybridization of biomarkers and sequential detection by combining signal removal and activation into a single step. Also disclosed are images obtained by such methods.

Probing of biological samples

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 R, R, R, R, R, R', R&#x2032;, R&#x2032;, R&#x2032; and R&#x2032; are selected form hydrogen, a protected C-Chydroxyalkyl group, or a C-Calkyl group; R, R&#x2032;are selected from a hydrogen, a hydroxyl, a protected hydroxyl group, a protected C-Chydroxyalkyl group, a C-Calkyl group; n is an integer between 0 and 4; R, R&#x2032;are selected from a hydrogen, a protecting group comprising C-Caliphatic radicals, C-Ccycloaliphatic radicals, C-Caromatic radicals, m is an integer between 1 and 10; at least one of Rand R&#x2032;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.

Contrast enhancement agents and method of use thereof

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

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 Ris independently at each occurrence a hydroxy group, a C-Chydroxyalkyl group, or a C-Calkyl group, and b is 0-4; R-Rare independently at each occurrence hydrogen, a C-Chydroxyalkyl group, or a C-Calkyl group, with the proviso that at least one of R-Ris a hydroxy group or a C-Chydroxyalkyl 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.

Hydroxylated contrast enhancement agents and imaging method

In one aspect, the present invention provides a contrast enhancement agent comprising an iron chelate having structure I and salts thereof wherein Ris independently at each occurrence a hydroxy group, a C-Chydroxyalkyl group, or a C-Calkyl group, and b is 0-4; R-Rare independently at each occurrence hydrogen, a C-Chydroxyalkyl group, or a C-Calkyl group, with the proviso that at least one of R-Ris a hydroxy group or a C-Chydroxyalkyl 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.

Hydroxylated contrast enhancement agents

In one aspect, the present invention provides a contrast enhancement agent comprising an iron chelate having structure I wherein Ris independently at each occurrence a hydroxy group, a C-Chydroxyalkyl group, or a C-Calkyl group, and b is 0-4; R-Rare independently at each occurrence hydrogen, a C-Chydroxyalkyl group, or a C-Calkyl group, with the proviso that at least one of R-Ris a hydroxy group or a C-Chydroxyalkyl 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.

In one aspect, the present invention provides a protected ligand precursor having structure XX wherein Ris independently at each occurrence a protected hydroxy group, a protected C-Chydroxyalkyl group, or a C-Calkyl group, and b is 0-4; R-Rare independently at each occurrence hydrogen, a protected C-Chydroxyalkyl group, or a C-Calkyl group, with the proviso that at least one of R-Ris a protected hydroxy group or a protected C-Chydroxyalkyl group; and Rand Rare independently at each occurrence a protecting group is selected from the group consisting of C-Caliphatic radicals, C-Ccycloaliphatic radicals, and C-Caromatic radicals.

Intermediates for hydroxylated contrast enhancement agents

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

Growing community of inventors

Saratoga Springs, NY, United States of America

Michael James Rishel