The University of Texas System

The Dow Chemical Company

Nordion (canada) Inc.

Psiloquest Inc.

Macrocyclics

Nordion Inc.

A Dean Sherry

Zoltan Kovacs

Garry E Kiefer

Craig R Malloy

Sara Chirayil

Veronica Clavijo Jordan

Jeroen Van Westrenen

William Jack Kruper, Jr

Kenneth J Balkus, Jr

William A Fordyce

Stuart W Young

Christian Preihs

Erno Brucher

Corinne Bensimon

Istvan Lazar

Ravichandran Ramasamy

Dhurjati S Mudigonda

Kuangcong Wu

Shanrong Zhang

Andre F Martins

Jing Yu

Khaled Nasr

Yunkou Wu

Cara L Ferreira

John Griffith Jones

Mark Woods

Navin Bansal

Piyu Zhao

F Mark Jeffrey

John G Jones

F M H Jeffrey

G Larry Cottam

Maria Veronica Clavijo Jordan

Matthew E Merritt

Gyula Tirsco

Zoltan Kovaks

In some aspects, the present disclosure provides gadolinium based sensors which may be used to image zinc ions in vivo. In some embodiments, the compounds show appropriate reactivity with zinc ions while maintaining high relaxivity to achieve improved background relative to other sensors.

Zinc sensors for in vivo imaging of beta-cell function by MRI

In some aspects, the present disclosure provides compounds of the formula: wherein the variables are defined herein. In some aspects, the present disclosure provides methods of preparing imaging agents, compositions thereof, and methods of imaging using said imaging agents or compositions thereof.

Mn(II)-based sensors to detect zinc in vivo with MRI

In some aspects, the present disclosure provides novel ligands, which may be used to make novel MRI contrast agents for the detection of zinc. In further aspects, by the present disclosure also provides methods of using as imaging agents and compositions thereof.

Gadolinium-based contrast agents for sensitive detection of Znwith MRI

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The present invention relates to the preparation of hyperpolarizedY. HyperpolarizedY may be used as nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) agents for sensitive detection and imaging.

Hyperpolarized 89-yttrium and methods relating thereto

A bifunctional polyazamacrocyclic chelating agent of the formula (I): wherein: and the variables A, L, Q, Q, X, Y, Z, Z, m, n and r are as defined in the description of the present application. Also described is a complex of the above chelating agent to an ion of a metal ion, such as an ion ofY,In orLu; a conjugate of the complex covalently attached to a biological carrier; and a pharmaceutical composition containing the conjugate. A method of therapeutic treatment of a mammal involving administration of the pharmaceutical composition is also described.

Bifunctional polyazamacrocyclic chelating agents

A bifunctional polyazamacrocyclic chelating agent of the formula (I): wherein: and the variables A, L, Q, Q, X, Y, Z, Z, m, n and r are as defined in the description of the present application. Also described is a complex of the above chelating agent to an ion of a metal ion, such as an ion ofY,Li orLu; a conjugate of the complex covalently attached to a biological carrier; and a pharmaceutical composition containing the conjugate. A method of therapeutic treatment of a mammal involving administration of the pharmaceutical composition is also described.

The present invention provides a combination of carbon-13 and deuterium metabolic tracers and methods that when used in conjunction with nuclear magnetic resonance spectroscopy, provide a measurement of metabolic fluxes in the target organisms. The tracers of the present invention may be taken orally during the same clinical exam. The metabolic information can be derived from blood, urine or other fluids to provide a comprehensive profile of glucogenic metabolism. The subject matter of the present invention may be applied to the study of metabolic dysfunction related to obesity, diabetes, HIV infection and a variety of other disease conditions.

Measurement of gluconeogenesis and intermediary metabolism using stable isotopes

The present invention is directed, in general, to a contrast agent comprising a tetraazacyclododecane ligand and comprising a macrocyclic ring and a paramagnetic metal ion coordinated to the tetraazacyclododecane ligand. Pendent arms R, R', R&#x2033; and R&#x2032;&#x2033; attached to a ring nitrogen. The pendent arms have the general formula: &#x2212;C&#x2032;HRRand for three or more of the pendant arms a chirality of the carbon atoms C&#x2032; are identical for each of three or more of the pendant arms. The Rgroup is larger than hydrogen and Ris selected from the group consisting of: an alcohol, amides, a carboxylate, phosphinates and a phosphonate. One or more substituents Ris a group larger than a methyl group and is located on one or more ring carbons.

Selection of coordination geometry to adjust water exchange rates of paramagnetic metal ion-based macrocyclic contrast agents

The present invention is directed, in general, to contrast agents (CA), and methods and systems of using such agents for producing image contrast based on a magnetization transfer (MT) mechanism. The CA comprises a tetraazacyclododecane ligand having pendent arms R, R', R&#x2033; and R&#x2032;&#x2033; that are amides having a general formula: &#x2014;CRH&#x2014;CO&#x2014;NH&#x2014;CH&#x2014;R. Rincludes organic substituents and Ris not hydrogen. A paramagnetic metal ion (M) is coordinated to the ligand. The method, comprises subjecting a CA, in a sample, to a radio frequency pulse. The CA has pendent arms R, R&#x2032;, R&#x2033; and R&#x2032;&#x2033; comprising organic substituents and the ligand further includes a M and a water molecule. A signal is obtained by applying a radio frequency pulse at a resonance frequency of the water molecule. The magnetic resonance system, comprises a magnetic resonance apparatus and the CA, the agent containing a ligand having the above described general formula.

Paramagnetic metal ion-based macrocyclic magnetization transfer contrast agents and method of use

The present invention is directed, in general, to a method for making high yields of functionalized cyclic or acyclic tertiary amine-containing compounds, termed active esters, the functionalized compounds themselves, and diagnostic or therapeutic systems incorporating such compounds. Ester groups are attached to all but one of its Nitrogen atoms of the tertiary amine-containing compound. Therefore, an active agent, in the presence of coupling agent, attaches to the remaining amine via a carboxylate group attached to the amine, to produce high yields of the active ester. The active ester is then combined with a biomolecule, to produce high yields of a bioconjugated product. A metal ion may be chelated to the bioconjugated product to produce a chelating agent for use in either diagnostic or therapeutic applications.

Preformed carboxylated active ester for labeling biomolecules

Process for making a chelating agent for labeling biomolecules using preformed active esters

A composition and method is disclosed for providing a magnetic resonance imaging contrast agent that is sensitive to pH, the compound and salts thereof including, a tetraaza base having a spacer at each of the amide groups, and a proton exchange attached to each of the spacer molecules, wherein the proton exchange group groups mediate proton exchange with water molecules that are trapped within the tetraaza base molecule.

pH sensitive MRI contrast agents

Simple equations that relate glucose, glutamate, glucuronate, and phenylacetylglutamine,C NMR multiplet areas to gluconeogenesis and pyruvate recycling during metabolism of &lsqb;1,2,3-,C,&rsqb;propionate are presented. This indicates that a direct measure of gluconeogenesis, pyruvate recycling, and anaplerosis may be obtained from a single,C NMR spectrum of suitably prepared blood or urine samples collected after oral administration of enriched propionate, acetaminophen, and phenylacetate.

Methods for determining gluconeogenesis, anapleurosis and pyruvate recycling

New methods for rapid, noninvasive determination of sodium ion in vivo are described. The methods are useful for assessing liver and other organ injury based on a nuclear magnetic resonance determination of intracellular and extracellular sodium in the damaged tissue. A shift reagent, TmDOTP.sup.5-, is used in vivo to produce baseline resolved peaks of .sup.23 Na. Excellent results are achieved with significantly less TmDOTP.sup.5- than with other conventional .sup.23 Na shift reagents such as DyTTHA.sup.3-. In contrast to use in isolated perfused heart tissue, TmDOTP.sup.5- solutions are employed in vivo without added calcium ion. The method has been applied to animal burn models. Results show that intracellular sodium ion levels are dramatically increased, thus providing a rapid assessment of liver function. Similar methods may be applied to the determination of intra- and extracellular potassium ion.

Determination of intracellular sodium and potassium ions by NMR

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Dallas, TX, United States of America

A Dean Sherry