Mallinckrodt, Inc.

Mallinckrodt Medical, Inc.

Mallinkrodt Inc.

Muthunadar P Periasamy

Raghavan Rajagopalan

Richard Bradley Dorshow

Samuel I Achilefu

Joseph E Bugaj

Rebecca A Wallace

Dennis A Moore

David H White

Steven R Woulfe

William P Cacheris

Robert W Weber

T Jeffrey Dunn

Hermo N Jimenez

Max D Adams

Lynn A deLearie

Brian D Doty

Milorad M Rogic

The present invention generally relates to nonionic x-ray contrast media formulations, radiological compositions containing such agents and methods for x-ray visualization utilizing such compositions. The invention especially relates to injectable radiological compositions for x-ray visualization comprising a pharmaceutically acceptable vehicle and a mixture of a monomer, being a triiodo-substituted benzene nucleus, and a dimer, being two linked triiodo-substituted benzene nuclei, such that the mixture demonstrates favorable properties.

Low osmolar X-ray contrast media formulations

Cyanine dye bioconjugates useful for diagnostic imaging and therapy are disclosed. The conjugates include several cyanine dyes with a variety of bis- and tetrakis (carboxylic acid) homologes. The compounds are be conjugated to bioactive peptides, carbohydrates, hormones, drugs, or other bioactive agents. The small size of the compounds allows more favorable delivery to tumor cells as compared to larger molecular weight imaging agents. The various dyes are useful over the range of 350 to 1,300 nm, the exact range being dependent upon the particular dye. The use of a biocompatible organic solvent such as dimethylsulfoxide helps to maintain the fluorescence of the compounds. The inventive compounds are useful for diagnostic imaging and therapy, in endoscopic applications for the detection of tumors and other abnormalities, for localized therapy, for photoacoustic tumor imaging, detection and therapy, and for sonofluorescence tumor imaging, detection and therapy.

Receptor-avid exogenous optical contrast and therapeutic agents

Cyanine and indocyanine dye compounds and bioconjugates are disclosed. The present invention includes several cyanine and indocyanine dyes, including bioconjugates of the same, with a variety of bis- and tetrakis (carboxylic acid) homologues. The compounds of the invention may be conjugated to bioactive peptides, carbohydrates, hormones, drugs, or other bioactive agents. The small size of compounds of the invention allows favorable delivery to tumor cells as compared to larger molecular weight imaging agents. Further, use of a biocompatible organic solvent such as dimethylsulfoxide may be said to assist in maintaining the fluorescence of compounds of the invention. The compounds and bioconjugates herein disclosed are useful in a variety of medical applications including, but not limited to, diagnostic imaging and therapy, endoscopic applications for the detection of tumors and other abnormalities, localized therapy, photoacoustic tumor imaging, detection and therapy, and sonofluorescence tumor imaging, detection and therapy.

Optical diagnostic and therapeutic agents and compositions

Highly hydrophilic indole and benzoindole derivatives that absorb and fluoresce in the visible region of light are disclosed. These compounds are useful for physiological and organ function monitoring. Particularly, the molecules of the invention are useful for optical diagnosis of renal and cardiac diseases and for estimation of blood volume in vivo.

Hydrophilic light absorbing compositions for determination of physiological function in critically ill patients

Minimally invasive physiological function monitoring agents

Cyanine dye bioconjugates useful for diagnostic imaging and therapy are disclosed. The conjugates include several cyanine dyes with a variety of bis- and tetrakis (carboxylic acid) homologs. The compounds may be conjugated to bioactive peptides, carbohydrates, hormones, drugs, or other bioactive agents. The small size of the compounds allows more favorable delivery to tumor cells as compared to larger molecular weight imaging agents. The various dyes are useful over the range of 350 to 1300 nm, the exact range being dependent upon the particular dye. The use of dimethylsulfoxide helps to maintain the fluorescence of the compounds. The inventive compounds are useful for diagnostic imaging and therapy, in endoscopic applications for the detection of tumors and other abnormalities, for localized therapy, for photoacoustic tumor imaging, detection and therapy, and for sonofluoresence tumor imaging, detection and therapy.

Tumor-targeted optical contrast agents

Cyanine and Indocyanine dye compounds and bioconjugates are disclosed. The present invention includes several cyanine and indocyanine dyes, including bioconjugates of the same, with a variety of bis- and tetrakis (carboxylic acid) homologues. The compounds of the invention may be conjugated to bioactive peptides, carbohydrates, hormones, drugs, or other bioactive agents. The small size of compounds of the invention allows favorable delivery to tumor cells as compared to larger molecular weight imaging agents. Further, use of a biocompatible organic solvent such as dimethylsulfoxide may be said to assist in maintaining the fluorescence of compounds of the invention. The compounds and bioconjugates herein disclosed are useful in a variety of medical applications including, but not limited to, diagnostic imaging and therapy, endoscopic applications for the detection of tumors and other abnormalities, localized therapy, photoacoustic tumor imaging, detection and therapy, and sonofluorescence tumor imaging, detection and therapy.

Dyes for organ function monitoring

Hydrophilic light absorbing compositions for determination of physiological function

The invention discloses compounds and compositions for dual phototherapy and combined therapy and diagnosis of tumors and other lesions. The compounds have a Dye that, when photoactivated, operates via Type I and/or Type II mechanisms. Other Dye or azide components may operate by the same or different mechanisms. Selection of particular components in a compound, and formulation of the compound(s) in a composition permit different activation wavelengths to be used for different therapies. A targeting moiety may be added to the compound or composition so that the Dye locates at a particular site, such as a hormone-sensitive tumor, for diagnosis and/or treatment. The compounds and compositions may be incorporated within liposomes.

Compounds for dual photodiagnosis and therapy

Light sensitive compounds for instant determination of organ function

The present invention provides new and structurally diverse compositions comprising compounds of the general formula: ##STR1## wherein A is N or CR.sub.1, R.sub.1 is hydrogen, C.sub.1 -C.sub.8 alkyl, or C.sub.6 -C.sub.10 aryl, where the alkyl or aryl group may be optionally substituted with one or more hydroxy, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.8 hydroxyalkyl, C.sub.1 -C.sub.8 alkoxy, C.sub.6 -C.sub.10 aryl, C.sub.6 -C.sub.10 hydroxyaryl, C.sub.6 -C.sub.10 aryloxy, --CO.sub.2 R.sub.2, --CONR.sub.3 R.sub.4, or NR.sub.3 R.sub.4 ; R.sub.2 -R.sub.7 are as defined within; g, h, i, j, k and m may be the same or different and are an integer from one to about six; X is --CO.sub.2 H, --PO.sub.3 H.sub.2, --SO.sub.3 H or --CONHOH. Methods for imaging including MRI, X-ray and radiation diagnosis using compositions of the invention are also provided.

Functionalized tripodal ligands for x-ray & radioactive imaging

Novel magnetic resonance imaging agents comprise complexes of paramagnetic ions with aminoalkylamide derivatives of diethylenetriaminepentaacetic acid ('DTPA') or ethylenediaminetetraacetic acid ('EDTA') or other polyaminocarboxylic or cyclic polyaminocarboxylic chelating agents, These novel imaging agents are characterized by excellent NMR image-contrasting properties and by high solubilities in physiological solutions. A novel method of performing an NMR diagnostic procedure involves administering to a warm-blooded animal an effective amount of a complex as described above and then exposing the warm-blooded animal to an NMR imaging procedure, thereby imaging at least a portion of the body of the warm-blooded animal.

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Chesterfield, MO, United States of America

Muthunadar P Periasamy