Mallinckrodt, Inc.

Mallinckrodt Medical, Inc.

Washington University

Mallinkrodt Inc.

Mallinkcrodt, Inc.

Medibeacon Inc.

Joseph E Bugaj

Raghavan Rajagopalan

Richard Bradley Dorshow

Samuel I Achilefu

Muthunadar P Periasamy

Gary Lee Cantrell

Mary Marmion Dyszlewski

Hermo N Jimenez

Ananthachari Srinivasan

Terry W Grogg

James J Benedict

Charles Raymond Degenhardt

Roger Alberto

Mahdi B Fawzi

B Daniel Burleigh

Barry F Van Duzee

Arthur H Combs

Jack L Erion

William B Jones

Michael Anthony Johnson

James R Duncan

Paul E Bates

Richard D Dorshow

Novel azo, azide, and sulfenate photoactive compounds and methods using the compounds for photodiagnostic and/or phototherapeutic procedures. The compounds have the formula E-L-DYE-X&#x2014;Y, wherein DYE is a photoactive component comprising a photoactive diagnostic agent, a photoactive type 1 agent, a photoactive type 2 agent, or a combination thereof;

Dye compounds as photoactive 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) 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

The present invention discloses dye-sulfenate derivatives and their bioconjugates for dual phototherapy of tumors and other lesions. The compounds of the present invention may contain either a mixture of Type 1 and Type 2 agents or a single entity that integrates both units in the same molecules. The compounds are designed to produce both Type 1 and Type 2 phototherapeutic effect at once using dual wavelength light source that will produce singlet oxygen and free radicals at the lesion of interest.

Dye-sulfenates for dual phototherapy

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

Dye-peptide conjugates useful for diagnostic imaging and therapy are disclosed. The dye-peptide conjugates include several cyanine dyes with a variety of bis- and tetrakis(carboxylic acid) homologues. 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 350-1300 nm, the exact range being dependent upon the particular dye. Use of dimethylsulfoxide helps to maintain the fluorescence of the compounds. The molecules of the invention are useful for diagnostic imaging and therapy, in endoscopic applications for the detection of tumors and other abnormalities and for localized therapy, for photoacoustic tumor imaging, detection and therapy, and for sonofluorescence tumor imaging, detection and therapy.

Versatile hydrophilic dyes

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

Methods using internal image antibodies for photodiagnosis and/or phototherapy. The internal image antibodies are conjugated with a photoactive molecule such as a dye or photosensitizer, to target specific regions, such as biological receptors. The photoactive molecules are then activated for diagnosis or therapy. Advantageously, the internal image antibody is specific for a biological receptor, but does not require isolation of the receptor to prepare the antibody, and provides the desired specificity and selectivity for targeted diagnosis or therapy.

Internal image antibodies for optical imaging and therapy

The present invention discloses novel sulfenate derivatives and their bioconjugates for phototherapy of tumors and other lesions. The sulfenates of the present invention are designed to absorb low-energy ultraviolet, visible, or near-infrared (NIR) region of the electromagnetic spectrum. The phototherapeutic effect is caused by direct interaction of free radicals, the reactive intermediate produced upon photofragmentation of the sulfenate moiety, with the tissue of interest.

Aromatic sulfenates for type 1 phototherapy

Dye-sulfenate derivatives and their bioconjugates for dual phototherapy of tumors and other lesions. The compounds comprise sulfenates having the formula, t,0080 where E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholecystekinin receptor binding molecules, steroid receptor binding molecules, and carbohydrate receptor binding molecules, and dihydoxyindolecarboxylic acid; L and X are independently selected from the group consisting of &#x2014;(R)NOC&#x2014;, &#x2014;(R)NOCCHO&#x2014;, &#x2014;(R)NOCCHCHO&#x2014;, &#x2014;OCN(R)&#x2014;, &#x2014;HNC(&#x2550;S)NH&#x2014;, and HNC(&#x2550;O)NH&#x2014;; DYE is an aromatic or a heteroaromatic radical derived from the group consisting of cyanines, indocyanines, phthalocyanines, rhodamines, phenoxazines, phenothiazines, phenoselenazines, fluoresceins, porphyrins, benzoporphyrins, squaraines, corrins, croconiums, azo dyes, methine dyes, indolenium dyes, crellins, and hypocrellins; Rto Rare independently selected from the group comprising hydrogen, C1-C10 alkyl, C5-C10 aryl, C1-C10 polyhydroxyalkyl, and C1-C10 polyalkoxyalkyl; and Ar is an aromatic or heteroaromatic radical derived from the group consisting of benzenes, naphthalenes, naphthoquinones, diphenylmethanes, fluorenes, anthracenes, anthraquinones, phenanthrenes, tetracenes, naphthacenediones, pyridines, quinolines, isoquinolines, indoles, isoindoles, pyrroles, imidiazoles, oxazoles, thiazoles, pyrazoles, pyrazines, purines, benzimidazoles, furans, benzofurans, dibenzofurans, carbazoles, acridines, acridones, phenanthridines, thiophenes, benzothiophenes, dibenzothiophenes, xanthenes, xanthones, flavones, coumarins, and anthacylines. The compounds are designed to produce both Type 1 and Type 2 phototherapeutic effects at once using a dual wavelength light source that will produce singlet oxygen and free radicals at the lesion of interest.

Cyanine-sulfenates for dual phototherapy

The present invention discloses dye-azide derivatives and their bioconjugates for dual phototherapy of tumors and other lesions. The compounds of the present invention may contain either a mixture of Type 1 and Type 2 agents or a single entity that integrates both units in the same molecules. The compounds are designed to produce both Type 1 and Type 2 phototherapeutic effect at once using dual wavelength light source that will produce singlet oxygen and nitrene at the lesion of interest.

Growing community of inventors

St. Charles, MO, United States of America

Joseph E Bugaj