Abstract: The invention relates to a process for preparing a liquid pharmaceutical formulation containing a complex of macrocyclic chelate with a lanthanide and a mol/mol amount of free macrocyclic chelate of between 0.002% and 0.4%, advantageously between 0.02% and 0.3% and very advantageously between 0.025% and 0.

Abstract: The present invention relates to contrast agents for magnetic resonance imaging (MRI). In particular, the present invention relates to MRI contrast agents that are activated in the presence of zinc(II) (e.g., resulting in a brighter image).

Abstract: Novel tetrapyrollic water soluble photosensitizing and imaging compounds and the methods of treating and imaging hyperproliferative tissue, e.g. tumors and hypervacularized tissue such as found in macular degeneration. Broadly, the compounds are tetrapyrollic photosensitizer compounds where the tetrapyrollic compound is a chlorin, bacteriochlorin, porphyrin, pyropheophorbide, purpurinimide, or bacteriopurpurinimide having 3 to 6 —CH2CONHphenylCH2CH(N(CH2COOH)2))(CH2N(CH2COOH)(CH2CH2N(CH2COOH)2)) groups or esters thereof or complexes thereof with gadolinium(III).

Abstract: The present invention relates to novel compounds of formula (I) and (II), compositions comprising compounds of formula (II) and their use as contrast agents in magnetic resonance (MR) imaging (MRI) and MR spectroscopy (MRS).

Abstract: The present invention relates to a ligand for metals, in particular lanthanides, of the general formula (I) A corresponds to an organic acid radical, to an alkyl or aryl ester. R1 and R2 correspond, individually and independently of one another, to an H, an alkyl radical or an aryl radical. Z1 and Z2, identical or different, are of the general formula (ZA) or (ZB): G represents an O, N, P, S or a C substituted independently with an H, an alkyl radical or an aryl radical. R3 to R8 correspond, individually and independently of one another, to an H, an alkyl radical or an aryl radical. The present invention also relates to co-ordinating complexes of the general formula: [Ln(L)(H2O)n] wherein Ln is a lanthanide, L corresponds to a ligand, as well as the grafting thereof to a molecule of interest and their preparation method. The present invention relates moreover to a contrast agent and a pharmaceutical composition including at least one ligand and/or complex and/or molecule of interest.

Abstract: Degradable macromolecular magnetic resonance imaging contrast agents for use in various diagnostic procedures, and methods for synthesizing, using and degrading these agents, are described. The macromolecule contrast agents disclosed in various aspects of this invention are degradable gadolinium compounds which show prolonged plasma retention, and enhanced permeability and retention in solid tumors, but are still capable of being rapidly cleared from the body.

Abstract: The present invention relates to the preparation of hyperpolarized 89Y. Hyperpolarized 89Y may be used as nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) agents for sensitive detection and imaging.

Abstract: The invention relates to a method for the Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy Imaging of a substrate molecule different from water wherein the NMR signal is enhanced by a reversible binding of the substrate molecule to a paramagnetic chelate complex, as well as to the use of a paramagnetic chelate complex in said method and the pharmaceutical composition for use therein.

Abstract: The present invention is directed to bioconjugates of complexes represented by the formula: wherein R, R?, R1, R?1, R2, R?2, R3, R?3, R4, R?4, R5, R?5, R6, R?6, R7, R?7, R8, R?8, R9, R?9, M, X, Y, Z and n are defined herein for use as contrast agents in diagnostic imaging.

Abstract: The invention relates generally to biotin-containing compounds that are useful as imaging agents and drug-delivery agents. Another aspect of the invention relates to the aforementioned compounds chelated to a metal atom. In a preferred embodiment, the metal atom is a gadolinium. Another aspect of the invention relates to a compound comprising three biotin moieties and a pharmaceutical agent covalently bound to a heterocyclic core. In certain embodiments, the pharmaceutical agent is an antibiotic, antiviral, or radionuclide. Another aspect of the present invention relates to a method of treating disease involving administering the compounds of the invention to a mammal. Another aspect of the present invention relates to a method of acquiring a magnetic resonance image using the compounds of the invention.

Abstract: The invention relates to bifunctional conjugates comprising a receptor ligand moiety and a metal binding moiety and complexes thereof with paramagnetic lanthanide or transition metals, and to the use of the metal complexes as contrast agents in magnetic resonance imaging (MRI) of tumors and other abnormalities.

Abstract: The invention relates generally to biotin-containing compounds that are useful as imaging agents and drug-delivery agents. Another aspect of the invention relates to the aforementioned compounds chelated to a metal atom. In a preferred embodiment, the metal atom is a gadolinium. Another aspect of the invention relates to a compound comprising three biotin moieties and a pharmaceutical agent covalently bound to a heterocyclic core. In certain embodiments, the pharmaceutical agent is an antibiotic, antiviral, or radionuclide. Another aspect of the present invention relates to a method of treating disease involving administering the compounds of the invention to a mammal. Another aspect of the present invention relates to a method of acquiring a magnetic resonance image using the compounds of the invention.

Abstract: Cyclen-based chelates can be used as contrast agents for multi-modal imaging of tissue cells. The cyclen-based chelates are preferably polyazamacrocyclic molecules formed from 1,4,7,10 tetraazacyclododecane (“cyclen”) having varying chelating ions, phosphoester chains, and light harvesting moieties. By changing the chelating ion, phosphoester chain length and/or the light harvesting moiety different imaging techniques, such as MRI, CT, fluorescence and absorption, x-ray and NIR, may be employed to image the tissue cells. Additionally, the cyclen-based chelates may be conjugated to provide for site-specific delivery of the cyclen-based chelate to the desired tissue cells. The cyclen-based chelates may also be delivered to the tissue cells by attaching the cyclen-based to a polymeric delivery vehicle. Although these cyclen-based chelates have a wide variety of application, the preferred use is for imaging of cancer cells, such as brain cancer, for improving resection of a cancerous tissue.

Abstract: The invention provides MRI contrast agents which provide a high sensitivity and which have an optimised body retention time. These agents enable the mapping of the local pH, temperature, oxygen concentration or other metabolites in a patient's body by the use of Chemical Exchange Saturation Transfer (CEST). Particularly pH and temperature mapping are useful for the detection of small cancer lesions and localised inflammation respectively.

Abstract: New compounds are provided that may be used to chelute a metal. The compound comprise polyazamacrocyclic compound with at least one phosphonic group substituted on at least one of the aza groups of the polyazamacrocyclic compound. Methods for preparing the compounds are also provided. Methods for preparing a diagnostic imaging agent using the compounds and methods for diagnostic imaging are further provided. Methods for preparing a therapeutic agent using the compounds and methods for therapy are further provided.

Abstract: Backbone-substituted 1,4,7,10-tetraaza cyclododecane-N,N?,N?,N??-tetraacetic acid compounds, metal complexes thereof, compositions thereof, conjugates thereof, and methods of use in diagnostic imaging and treatment of a cellular disorder.

Abstract: The invention relates to novel magnetic resonance imaging contrast agents and methods of detecting physiological signals or substances.

Abstract: Novel metal-chelate complexes comprising aminocarboxylate ligands including substituted aromatic amide moieties, such as those having the formula wherein R13, A1, R1 and R2 are as defined herein, are disclosed.

Abstract: The invention relates to the use of perfluoroalkyl-containing metal complexes that have a critical micelle formation concentration <10?3 mol/l, a hydrodynamic micelle diameter (2 Rh)>1 nm and a proton relaxivity in plasma (R1)>10 l/mmol·s as contrast media in MR imaging for visualization of intravascular thrombi.

Abstract: The invention relates to a method and a corresponding device for multipurposely supporting a randomly shaped and/or possibly complex with respect to a rigid base (11) part (1) by fixing a working reference, wherein the inventive method consist in interposing at least one deformable constant-volume chamber (3) which is sealed and filled with incompressible particles (4) between a maintainable part and the rigid base (11) and in lowing pressure inside the deformable constant-volume chamber (3) by means of a vacuum source (5) connectable thereto, thereby enabling the particles (4) to be amalgamated into a solid block which thrusts at least partly on the rigid base (11) and maintains the part (1) by fitting the shape thereof.

Abstract: A new use in magnetic resonance imaging employing a field greater than 1.5 Tesla, of a porphyrin compound of the following general formula I is provided: in which R0 and R?0 are such that the compound is soluble in a biological medium, and M denotes a paramagnetic metal ion, advantageously Mn3+. The present invention also relates to novel porphyrin compounds.

Abstract: Cyclen-based chelates can be used as contrast agents for multi-modal imaging of tissue cells. The cyclen-based chelates are preferably polyazamacrocyclic molecules formed from 1,4,7,10 tetraazacyclododecane (“cyclen”) having varying chelating ions, phosphoester chains, and light harvesting moieties. By changing the chelating ion, phosphoester chain length and/or the light harvesting moiety different imaging techniques, such as MRI, CT, fluorescence and absorption, x-ray and NIR, may be employed to image the tissue cells. Additionally, the cyclen-based chelates may be conjugated to provide for site-specific delivery of the cyclen-based chelate to the desired tissue cells. The cyclen-based chelates may also be delivered to the tissue cells by attaching the cyclen-based chelates to a polymeric delivery vehicle. Although these cyclen-based chelates have a wide variety of application, the preferred use is for imaging of cancer cells, such as brain cancer, for improving resection of a cancerous tissue.

Abstract: A multifunctional cross-bridged tetraaza macrocyclic compound has at least one side arm that comprises a moiety that is capable of forming a bond with another molecule, which has a targeting moiety that directs the compound to a site a marker substance. The compound is chelated to a medically active material that generates a signal for diagnostic imaging or produces a therapeutic effect at the site of the marker substance. A method for detecting, diagnosing, and/or treating a disease that produces the marker substance uses a conjugate comprising the multifunctional cross-bridged tetraaza macrocyclic compound.

Abstract: The invention relates to the use of metal complexes that contain at least one perfluorinated alkyl radical and at least one chelating agent radical and at least one metal ion equivalent of the atomic numbers 21-29, 31-33, 37-39, 42-44, 49 or 57-83, as well as salts thereof for the production of a diagnostic agent for visualizing amyloid-containing plaques.

Abstract: The present invention relates generally to the fields of chemistry and radionuclide imaging. More particularly, it concerns compositions, kits and methods for imaging and therapy involving N4 compounds and derivatives.

Abstract: MRI contrast agents that employ paramagnetic agents and chemical exchange saturation transfer (paraCEST) and which are coupled to targeted particulate delivery vehicles provide sufficient concentration of the paraCEST contrast agents to obtain useful images of target tissues or organs. In addition, the image contrast may be switched on or off with a presaturation radio frequency pulse, avoiding the necessity obtaining pre-injection and post-injection images.

Abstract: The invention relates to contrast agents for magnetic resonance imaging comprising a chelating ligand and a transition metal ion, said ligand carrying a substituent capable of reacting chemically or biochemically with a target substance while bringing about a change in the spin state.

Abstract: The present invention relates to a polyamine-substituted ligand for the preparation of a contrast agent derived from a chelating molecule selected from the group consisting of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and diethylentriamine-pentaacetic acid (DTPA), wherein at least one of the carboxylic groups of the chelating molecule is reacted with an amine of formula HNR1R2 to form an amide bond, wherein R1, R2 are independently selected from the group consisting of H; (CH2)n—NR3R4; and R5; R3, R4 are independently selected from the group consisting of H; (CH2)m—NR6R7; and (CH2)m-1—CH3; R6, R7 are independently selected from the group consisting of H; and (CH2)o-1—CH3; n, m, o are independently 2, 3, or 4; R5 is of formula and optionally at least one of the carboxylic groups of the chelating molecule is further reacted with a monoalkylamine having 1 to 18 carbon atoms to form an amide bond; provided that at least one of R1, R2 is other than H.

Abstract: The invention relates to new, monomeric, perfluoroalkyl-substituted metal complexes, processes for their production, and their use in diagnosis and therapy. The compounds according to the invention are suitable especially as in vivo contrast media in nuclear spin tomography (MRT). They can preferably be used as blood-pool agents and as lymphographic agents.

Abstract: An adamantane functionalized magnetic resonance imaging (MRI) contrast agent has been synthesized, and shows high liver specificity, prolonged retention time in both the liver and kidneys, the highest relaxivity among clinical contrast agents, high water solubility, thermodynamic stability, signal intensity enhancement, hepatocellular uptake, and low osmolality and toxicity.

Abstract: The invention relates to high-relaxivity macrocyclic gadolinium chelate oligomers of formula W-(A)m in which W, A and m are as defined in claim 1, and their use as a blood pool contrast product for magnetic resonance imaging.

Abstract: Described are new cascade polymer complexes, compositions containing them and use of the complexes in diagnosis and therapy, particularly for magnetic resonance imaging and computer tomography imaging.

Abstract: The metal complexes of general formula I in which Hal stands for bromine or iodine and A1 and A2 have different meanings, are suitable as contrast media.

Abstract: The invention relates to metal complex compounds, contrast agents for MRI and in vivo NMR markers for NMR spectroscopy comprising said metal complex compounds and methods for in vivo determination of physiological parameters, e.g. enzyme activity or pH using said metal complex compounds.

Abstract: Disclosed are CEST paramagnetic agents comprising a substrate (SH) containing mobile protons bonded to a para-magnetic chelate (SR) containing a metal selected from iron (11) (high-spin configuration), iron (111), cobalt (11), rhodium (11), copper (11), nickel (11), cerium (111), praseodymium (111), neodymium (111), dysprosium (111), erbium (111), terbium (111), holmium (111), thulium (III), ytterbium (III) and europium (111).

Abstract: The invention relates to the subjects that are characterized in the claims, namely perfluoroalkyl-containing metal complexes with an N-alkyl group of general formula 1, process for their production and their use in NMR and x-ray diagnosis, radiodiagnosis, and radiotherapy, as well as in MRT lymphography.

Abstract: The present invention relates to contrast agents for diagnostic imaging with prolonged blood retention. In particular, this invention relates to novel compounds that are characterized by an image enhancing moiety (IEM); a protein plasma binding moiety (PPBM); and a blood half-life extending moiety (BHEM). This invention also relates to pharmaceutical compositions comprising these compounds and to methods of using the compounds and compositions for blood half-life extension and contrast enhancement of diagnostic imaging.

Abstract: The present invention relates to contrast agents for diagnostic imaging with prolonged blood retention. In particular, this invention relates to novel compounds that are characterized by an image enhancing moiety (IEM); a protein plasma binding moiety (PPBM); and a blood half-life extending moiety (BHEM). This invention also relates to pharmaceutical compositions comprising these compounds and to methods of using the compounds and compositions for blood half-life extension and contrast enhancement of diagnostic imaging.

Abstract: The invention relates to conjugates that consist of macrocyclic metal complexes with biomolecules and their production. The conjugates are suitable as contrast media in NMR diagnosis and radiodiagnosis as well as as agents for radiotherapy. High relaxivity is achieved by a special liganding of macrocyclic compounds, and a fine-tuning of the relaxivity is made possible.

Abstract: Substituted 1,4,7-triazacyclononane-N,N?,N?-triacetic acid compounds with a pendant donor amino group, metal complexes thereof, compositions thereof, and methods of use in diagnostic imaging and treatment of a cellular disorder.

Abstract: The present invention relates to contrast agents for diagnostic imaging with prolonged blood retention. In particular, this invention relates to novel compounds that are characterized by an image enhancing moiety (IEM); a protein plasma binding moiety (PPBM); and a blood half-life extending moiety (BHEM). This invention also relates to pharmaceutical compositions comprising these compounds and to methods of using the compounds and compositions for blood half-life extension and contrast enhancement of diagnostic imaging.

Abstract: The present invention relates to improved diagnostic agents for Magnetic Resonance Imaging and optical imaging. In particular, this invention relates to MRI and optical imaging agents that allow for the sensitive detection of a specific bioactivity within a tissue. These agents are prodrug contrast agents which are bioactivated in vivo in the presence of the specific bioactivity. This invention also relates to pharmaceutical compositions comprising these agents and to methods of using the agents and compositions comprising the agents.

Abstract: Chelating ligands and metal chelates useful as CEST MR contrast agents are disclosed. The CEST agents can be used to evaluate blood volume changes in the heart and brain.

Abstract: The invention relates to pharmaceutical agents that contain at least one fluoroalkyl-containing metal complex that has a critical micelle-formation concentration of <10?3 mol/l and a hydrodynamic micelle diameter (2Rh) of >1 nm, and at least one natural or synthetic epothilone or epothilone derivative, optionally with the additives that are commonly used in galenicals.

Abstract: The invention relates to novel compounds that are useful for the diagnosis of many pathologies, in particular cardiovascular, cancer-related and inflammatory pathologies, and to pharmaceutical compositions comprising said compounds. These compounds comprise a component for targeting a pathological region, linked to a detection component which is effective in diagnostic terms.

Abstract: The invention provides methods and compositions for molecular resonance imaging of membrane potential. The compositions comprise an indicator moiety attached through an optional linker to a macrocycle component that binds a lanthanide. The indicator moiety changes conformation in response to alterations in membrane potential and alters the interaction of the bound lanthanide with water. This alteration produces a detectable change in MRI signal , notably the T1 value. A preferred indicator moiety is spiropyran as it exhibits membrane-potential driven interconversions between the closed-ring spiropyran conformer and the extended merocyanine conformer. A preferred macrocycle is DO3A, known to bind gadolinium and an established MRI contrast agent. The methods of the invention comprise in vivo and in vitro uses of compositions of the invention to obtain MRI images that provide information about membrane potential.

Abstract: Novel chelants and other compounds, and compositions thereof are provided, that are useful for detection and treatment of cancer and other abnormal and disease-state cells and tissues.

Abstract: Backbone-substituted 1,4,7,10-tetraaza cyclododecane-N,N?,N?,N??-tetraacetic acid compounds, metal complexes thereof, compositions thereof, conjugates thereof, and methods of use in diagnostic imaging and treatment of a cellular disorder.

Abstract: Substituted 1,4,7-triazacyclononane-N,N?,N?-triacetic acid compounds with a pendant donor amino group, metal complexes thereof, compositions thereof, and methods of use in diagnostic imaging and treatment of a cellular disorder.

Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described. Also, clearing agents, anti-ligand-targeting moiety conjugates, target cell retention enhancing moieties and additional methods are discussed.