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 a novel class of magnetic resonance imaging agents that can cross the blood brain barrier and provide accurate magnetic resonance imaging of the brain, especially magnetic resonance images of amyloid deposits associated with Alzheimer's disease.

Abstract: 1,4,7,10-Tetraazacyclodedecane butyltriols of general formula IA in which R1 means hydrogen or a metal ion equivalent independent of one another and R2 means a butyltriol radical as well as their salts with organic or inorganic bases or amino acids are valuable pharmaceutical agents.

Abstract: Potential magnetic resonance imaging (MRI) contrast agents that are functionalized with crown compounds have been synthesized, and show target-specificity to the kidney and liver, along with excellent water solubility, high MR intensity enhancement efficiency, long resident lifetime, low dosage requirement, low cytotoxicity and prolonged excretion rate.

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: Compounds useful for associating with nanoparticle or microparticle emulsions to obtain magnetic resonance images permit control of the relaxivity of the signal and readily associate with the particulate components. The compounds are conveniently prepared from achiral derivatives of chelating moieties.

Abstract: Thus the present invention describes diagnostic agents comprising a diagnostic metal and a compound, wherein the compound comprises: 1-10 targeting moieties; a chelator; and 0-1 linking groups between the targeting moiety and chelator; wherein the targeting moiety is a matrix metalloproteinase inhibitor; and wherein the chelator is capable of conjugating to the diagnostic metal. The present invention also provides novel compositions of the compounds of the invention, kits, and their uses in diagnosis of diseases associated with MMPs.

Abstract: The present invention provides a class of biochemically-activated MRI contrast agents. The agents include a paramagnetic chelate attached via a linker arm to a relaxivity-modulating group. When the relaxivity-modulating group is removed or otherwise interacts with a targeted substance, the agents are activated by various mechanisms. The activation is detectable by an increase or decrease in the relaxivity of the metal chelate. The agents are useful in the detection of biochemical parameters in cells, tissues and subjects. Exemplary biochemical parameters are markers that are associated with disease states.

Abstract: 1,4,7,10-Tetraazacyclodedecane butyltriols of general formula IA in which R1 means hydrogen or a metal ion equivalent independent of one another and R2 means a butyltriol radical as well as their salts with organic or inorganic bases or amino acids are valuable pharmaceutical agents.

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: 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: 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: 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: Cyclic polyaza chelators that possess high affinity and specificity for first transition series metal cations exhibit an unanticipated improvement in biological activity when administered as complexes with cations of the alkaline earth metals, Ca(II) and Mg(II), most notably Ca(II). By virtue of this improvement, these complexes are particularly effective in the treatment of pathological conditions, including ischemia and ischemia-reperfusion injury.

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 I/mmol.s) as contrast media in MR imaging for visualization of plaque, lymph nodes, infarcted and necrotic tissue and for independent visualization of necrotic tissue and tumor tissue.

Abstract: 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? and R?? that are amides having a general formula: —CR1H—CO—NH—CH2—R2. R1 includes organic substituents and R2 is 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?, R? and R?? 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.

Abstract: The present invention relates to cryptate compounds useful as chelating agents. In particular, the present invention relates to functionalized derivatives of certain cryptate compounds. These functionalized derivatives are suitable for use in radiolabelling and similar applications. The present invention also relates to a method for diagnosis or therapy of a disease utilizing functionalized derivatives of cryptase compounds.

Abstract: The metal complexes of general formula I 1

Abstract: Polymerized liposome particles which are linked to a targeting agent and may also be linked to a contrast enhancement agent and/or linked to or encapsulating a treatment agent. The targeting imaging enhancement polymerized liposome particles interact with biological targets holding the image enhancement agent to specific sites providing in vitro and in vivo study by magnetic resonance, radioactive, x-ray or optical imaging of the expression of molecules in cells and tissues during disease and pathology. Targeting polymerized liposomes may be linked to or encapsulate a treatment agent, such as, proteins, drugs or hormones for directed delivery to specific biological sites for treatment.

Abstract: The invention concerns a racemic compound of the pair of enantiomers of formula (III) wherein R represents an alkyl group or a phenyl group optionally substituted.

Abstract: The present invention provides a cyclic tetrapeptide derivative represented by the following general formula (I) or a pharmaceutically acceptable salt thereof: wherein each of R21 and R22 independently denotes hydrogen, a linear C1-C6-alkyl group to which a non-aromatic cycloalkyl group or an optionally substituted aromatic ring may be attached, or a branched C3-C6-alkyl group to which a non-aromatic cycloalkyl group or an optionally substituted aromatic ring may be attached; and each of R1 and R3 independently denotes a linear C1-C5-alkylene group which may have a C1-C6 side chain, in which the side chain may form a condensed ring structure on the alkylene chain. The present invention also provides a histone deacetylase inhibitor, an MHC class-I molecule expression-promoting agent and a pharmaceutical composition, each of which comprises the above cyclic tetrapeptide derivative or pharmaceutically acceptable salt thereof as an active ingredient.

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 plaque, lymph nodes, infarcted and necrotic tissue and for independent visualization of necrotic tissue and tumor tissue.

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: Novel methods, processes and metal complexes attached to a hypoxia-localizing moiety comprising

Abstract: The present invention provides an &agr;-particle-emitting radioisotope chelation complex comprising 225Actinium (225Ac) and 1,4,7,10,13,16-hexaazacyclohexadecane-N,N′,N′,N′,N′,N′-hexaacetic acid (HEHA) (225Ac-HEHA). Also provided is a bifunctional HEHA, and a bifunctional 225Ac-HEHA. The bifunctional HEHA and the bifunctional 225Ac-HEHA can be conjugated to a targeting agent. In view of the above, the present invention provides a method of making HEHA and methods of making a bifunctional HEHA, including a conjugate thereof Also provided are a method of treating disease, a method of treating cancer, a method of decontaminating a sample from 225Ac, a method of decontaminating a person who has been externally contaminated with 225Ac, and a method of detoxifying a person who has internalized 225Ac.

Abstract: The invention relates to novel magnetic resonance imaging contrast agents that report on physiological events in a conditional fashion and simultaneously detect the delivery and/or activation of a therapeutically active agent.

Abstract: A novel dual functioning excipient for metal chelate contrast agents is disclosed.

Abstract: 1,4,7,10-Tetrazacyclododecanes carrying a side chain terminating in a group capable of reacting with an antibody, and their complexes with a di- or tripositive metal having a coordination number of 6 or more can be used to prepare imaging agents. Typical metals are indium, copper, lead, bismuth, yttrium, terbium, gadolinium, and scandium. The compounds can be reacted with a monoclonal or polyclonal antibody or antibody fragment to target the metal to a specific type of tissue.

Abstract: The present invention is directed to bioconjugates of complexes represented by the formula: 1

Abstract: Metal chelates capable of exhibiting an immobilized relativity between about 60 and 200 mM−1s−1/metal atom are useful as magnetic resonance imaging agents.

Abstract: The invention relates to a process for reducing the fluorescence quenching caused by the measuring medium in a fluorescence assay, by introducing into said medium of rare earth metal cryptates which are not very sensitive to this fluorescence quenching, said rare earth metal cryptates comprising at least one pyridine radical which is substituted one or more times or unsubstituted.

Abstract: A new class of polychelants, their chelates with metal ions and their physiologically acceptable salts, useful, either as they are or in association or formulation with other components, for diagnostic imaging as general or specific contrast agents for specific tissues, organs or body compartments.

Abstract: This invention relates to macrocyclic chelants comprised of one or two heteroatom-containing bridges, compositions containing them and their use in medicine, particularly in diagnostic imaging and radiotherapy. This invention relates especially to the use of metal chelates of the macrocyclic chelants as metallopharmaceuticals in Magnetic Resonance Imaging (MRI) and radiopharmaceuticals. This invention also relates to macrocyclic chelants as bifunctional chelating agents (BFC's) for the labeling of biologically active targeting molecules such as proteins, peptides, peptidomimetics, and non-peptide receptor ligands, with metal ions and radioisotopes.

Abstract: Formula (I) compounds are described where the groups are as defined here below, processes for their preparation, and their uses for the preparation of conjugates with radionuclides for use in human and animal therapy and diagnostics, particularly for the diagnosis and therapy of pathological conditions such as tumours.

Abstract: The present invention relates to pharmaceutical compositions and methods for using said compositions which comprise:

Abstract: The invention relates to novel magnetic resonance imaging contrast agents and methods of delivering therapeutically active agents.

Abstract: The present invention is directed to bioconjugates of complexes represented by the formula: 1

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 bloactivity 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: Perfluoroalkyl-containing complexes with polar radicals of general formula I (K)1-G-(Z-Rf)m(R)p  (I) in which R means the polar radical, Rf means a perfluorinated carbon chain, K is a metal complex, and Z represents a linker group, are suitable for intravenous lymphography, for tumor diagnosis and for infarction and necrosis imaging.

Abstract: The invention relates to novel magnetic resonance imaging contrast agents for imaging cancer.

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 invention provides a composition of matter of the formula (I): V-L-R where V is an organic group having binding affinity for an angiotensin II receptor site, L is a linker moiety or a bond, and R is a moiety detectable in in vivo imaging of a human or animal body, with the provisos that where V is angiotensin or a peptidic angiotensin derivative or analog then V-L-R is other than a non-metal radionuclide substituted peptide (e.g. 125I substituted angiotensin II) and L-V is other than simply a peptide with a chelating agent amide bonded to a side chain thereof. This composition of matter may be used to image cardiovascular diseases and disorders.

Abstract: The invention relates to novel magnetic resonance imaging contrast agents.

Abstract: The present invention relates to contrast agents for diagnostic imaging. In particular, this invention relates to novel multimeric compounds which exhibit improved relaxivity properties upon binding to endogenous proteins or other physiologically relevant sites. The compounds consist of: a) two or more Image Enhancing Moieties (IEMs) (or signal-generating moiety) comprising multiple subunits; b) two or more Target Binding Moieties (TBMs), providing for in vivo localization and multimer rigidification; and c) a scaffold framework for attachment of the above moieties. d) optional linkers for attachment of the IEMs to scaffold. This invention also relates to pharmaceutical compositions comprising these compounds and to methods of using the compounds and compositions for contrast enhancement of diagnostic imaging.

Abstract: Improved metal complex-containing pharmaceutical agents are described which, as an additive, contain one or more complexing agents and/or one or more weak metal complex(es) or mixtures thereof.

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: Perfluoroalkyl-containing complexes with sugar radicals of general formula I in which R represents a monosaccharide or oligosaccharide radical that is bonded via the 1-OH position or 1-SH position, Rf means a perfluorinated carbon chain, K is a metal complex, and Y and Z represent linker groups, are suitable for intravenous lymphography, for tumor diagnosis and for infarction and necrosis imaging.

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: Compounds of formula (I) and (II) wherein the R, R1, R2, R3 and R4 groups have the meanings defined in the disclosure, are useful chelants for metal ions. The complexes of compounds (I) and (II) with paramagnetic ions are useful as contrast agents for M.R.I. imaging.