Abstract: A compound that is a conjugate of an antagonist to an integrin expressed by a tumor cell and at least one of a tumor avid tetrapyrollic photosensitizer, a fluorescent dye, and a radioisotope labeled moiety wherein the radioisotope is 11C, 18F, 64Cu, 124I, 99Tc, 111In or GdIII and its method of use for diagnosing, imaging and/or treating hyperproliferative tissue such as tumors. Preferably the photosensitizer is a tumor avid tetrapyrollic photosensitizer, e.g. a porphyrin, chlorin or bacteriochlorin, e.g. pheophorbides and pyropheophorbides. Such conjugates have extreme tumor avidity and can be used to inhibit or completely destroy the tumor by light absorption. The integrin is usually ?v?3, ?5?1, ?v?5, ?4?1, or ?2?1. Preferably, the antagonist is an RGD peptide or another antagonist that may be synthetic such as a 4-{2-(3,4,5,6-tetra-hydropyrimidin-2-ylamino)ethyloxy}-benzoyl]amino-2-(S)-amino-ethyl-sulfonylamino group.

Abstract: This invention describes a first report on the synthesis of certain 124I-labelled photosensitizers related to chlorines and bacteriochlorins with long wavelength absorption in the range of 660-800 nm. In preliminary studies, these compounds show a great potential for tumor detection by positron emission tomography (PET) and treatment by photodynamic therapy (PDT). The development of tumor imaging or improved photodynamic therapy agent(s) itself represent an important step, but a dual function agent (PET imaging and PDT) provides the potential for diagnostic body scan followed by targeted therapy.

Abstract: A nanoparticle including a polysiloxane base having an exterior surface and having a photosensitizer at least partly exposed at its exterior surface, said photosensitizer being secured to the exterior surface by loading the photosensitizer onto the surface after formation of the polysiloxane base of the nanoparticle. The nanoparticle may have tumor targeting moieties and may be post loaded with cyanine dye. The nanoparticle preferably includes post loaded moieties providing at least two of tumor specificity, photodynamic properties and imaging capabilities and the photosensitizer is tagged with a radioisotope. A method for preparation of the nanoparticle is also provided.

Abstract: Tetrapyrollic photosensitizers and imaging agent compounds having A, B, C, and D rings and having a reduced B ring and an oxidized D ring. The compounds preferably have a purity of at least 95 percent and preferably have a fused system connected at an unsaturated carbon atom of the C ring nearest the D ring and at the unsaturated carbon atom between the C and D rings. The invention also includes a method of making the compounds at over 95 percent yield by starting with a B and D ring oxidized tetrapyrollic compound and dissolving it in a halogenated hydrocarbon solvent and treating it with sufficient nitroalkane solution of FeCl3.6H2O to oxidize the D ring and separating the resulting organic layer and drying.

Abstract: A compound that is a conjugate of an antagonist to an integrin expressed by a tumor cell and at least one of a tumor avid tetrapyrollic photosensitizer, a fluorescent dye, and a radioisotope labeled moiety wherein the radioisotope is 11C, 18F, 64Cu, 124I, 99Tc, 111In or GdIII and its method of use for diagnosing, imaging and/or treating hyperproliferative tissue such as tumors. Preferably the photosensitizer is a tumor avid tetrapyrollic photosensitizer, e.g. a porphyrin, chlorin or bacteriochlorin, e.g. pheophorbides and pyropheophorbides. Such conjugates have extreme tumor avidity and can be used to inhibit or completely destroy the tumor by light absoption. The integrin is usually ?v?3, ?5?1, ?v?5, ?4?1, or ?2?1. Preferably, the antagonist is an RGD peptide or another antagonist that may be synthetic such as a 4-{2-(3,4,5,6-tetra-hydropyrimidin-2-ylamino)ethyloxy}-benzoyl]amino-2-(S)-amino-ethyl-sulfonylamino group.

Abstract: A compound having preferential localization in tumor tissue relative to normal tissue, a preferential electromagnetic absorption at a wavelength between about 660 and 900 nm, and a fluorescence at a wavelength shifted from the preferential absorption by at least +30 nm and preferably at least +50 nm. The compound further preferably destroys tumor tissue in which it is absorbed when exposed to light at its preferential absorption wavelength. In a preferred embodiment of the invention, the compound is a conjugate of a tumor avid tetrapyrrole compound with a fluorescent dye, and more preferably the fluorescent dye is an indocyanine dye such as indocyanine green. The tumor avid tetrapyrrole compound is preferably a porphyrin derivative selected from the group consisting of chlorins, bacteriochlorins, purpurins and derivatives thereof.

Abstract: A tetrapyrollic photosensitizer compound having at least one pendant —CH2CH2CON(CH2CON(CH2COOH)2)2 or —N(CH2COOH)2 group or esters thereof said tetrapyrollic compound being a chlorin, bacteriochlorin, porphyrin, pyropheophorbide, purpurinimide, or bacteriopurpurinimide. Desirably the compound has the formula: or a pharmaceutically acceptable derivative thereof, wherein R1—R8 and R10 are various substituents and R9 is substituted or unsubstituted —CH2CH2CON(CH2CON(CH2COOH)2)2; or —N(CH2COOH)2. The invention also includes a method of treatment by photodynamic therapy by treatment with light after injecting the compound and a method of imaging by fluorescence after injection of the compound.

Abstract: A tetrapyrollic photosensitizer compound having at least one pendant —CH2CH2CON(CH2CON(CH2COOH)2)2 or —N(CH2COOH)2 group or esters thereof said tetrapyrollic compound being a chlorin, bacteriochlorin, porphyrin, pyropheophorbide, purpurinimide, or bacteriopurpurinimide. Desirably the compound has the formula: or a pharmaceutically acceptable derivative thereof, wherein R1-R8 and R10 are various substituents and R9 is substituted or unsubstituted —CH2CH2CON(CH2CON(CH2COOH)2)2; or —N(CH2COOH)2. The invention also includes a method of treatment by photodynamic therapy by treatment with light after injecting the compound and a method of imaging by fluorescence after injection of the compound.

Abstract: A method for treating hyperproliferative tissue in a mammal which tissue expresses ABCG2 including the steps of: a) systemically introducing from about 100 to about 1000 mg/kg of body weight of a tyrosine kinase inhibiting compound into the mammal; b) within from about 0.5 to about 24 hours after the introducing in step a) systemically introducing from about 0.05 to about 0.5 ?mol per kilogram of body weight of a tumor avid photosensitizing compound, that acts as a substrate for ABC family transport protein, ABCG2 and that has a preferential light absorbance frequency; and c) exposing the hyperproliferative tissue to light at a fluence of from about 50 to about 150 J/cm2 delivered at a rate of from about 5 to about 25 mW/cm2 at the light absorbance frequency.

Abstract: This invention describes a first report on the synthesis of certain 124I-labelled photosensitizers related to chlorines and bacteriochlorins with long wavelength absorption in the range of 660-800 nm. In preliminary studies, these compounds show a great potential for tumor detection by positron emission tomography (PET) and treatment by photodynamic therapy (PDT). The development of tumor imaging or improved photodynamic therapy agent(s) itself represent an important step, but a dual function agent (PET imaging and PDT) provides the potential for diagnostic body scan followed by targeted therapy.

Abstract: A tetrapyrollic photosensitizer compound having at least one pendant —CH2CH2CON(CH2CON(CH2COOH)2)2 or —N(CH2COOH)2 group or esters thereof said tetrapyrollic compound being a chlorin, bacteriochlorin, porphyrin, pyropheophorbide, purpurinimide, or bacteriopurpurinimide. Desirably the compound has the formula: or a pharmaceutically acceptable derivative thereof, wherein R1-R8 and R10 are various substituents and R9 is substituted or unsubstituted —CH2CH2CON(CH2CON(CH2COOH)2)2; or —N(CH2COOH)2. The invention also includes a method of treatment by photodynamic therapy by treatment with light after injecting the compound and a method of imaging by fluorescence after injection of the compound.

Abstract: A tetrapyrollic photosensitizer compound having at least one pendant —CH2CH2CON(CH2CON(CH2COOH)2)2 or —N(CH2COOH)2 group or esters thereof said tetrapyrollic compound being a chlorin, bacteriochlorin, porphyrin, pyropheophorbide, purpurinimide, or bacteriopurpurinimide. Desirably the compound has the formula: or a phamaceutically acceptable derivative thereof, wherein R1-R8 and R10 are various substituents and R9 is substituted or unsubstituted —CH2CH2CON(CH2CON(CH2COOH)2)2; or —N(CH2COOH)2. The invention also includes a method of treatment by photodynamic therapy by treatment with light after injecting the compound and a method of imaging by fluorescence after injection of the compound.

Abstract: A compound having preferential localization in tumor tissue relative to normal tissue, a preferential electromagnetic absorption at a wavelength between about 660 and 900 nm, and a fluorescence at a wavelength shifted from the preferential absorption by at least +30 nm and preferably at least +50 nm. The compound further preferably destroys tumor tissue in which it is absorbed when exposed to light at its preferential absorption wavelength. In a preferred embodiment of the invention, the compound is a conjugate of a tumor avid tetrapyrrole compound with a fluorescent dye, and more preferably the fluorescent dye is an indocyanine dye such as indocyanine green. The tumor avid tetrapyrrole compound is preferably a porphyrin derivative selected from the group consisting of chlorins, bacteriochlorins, purpurins and derivatives thereof.

Abstract: A method for treatment of hyperproliferative tissue which by exposing the hyperproliferative tissue to a sufficient quantity of a purified iridoid compound to inhibit its growth, where the iridoid compound includes a polysubstituted cyclopenta(c)dihydropyran where the cyclopenta ring is substituted at its 2? position with a ketofuryl group, where the numbering of the fused cyclopenta(c)dihydropyran ring structure includes heterocyclic oxygen, is counterclockwise and begins at the first carbon atom counterclockwise from the cyclopenta ring so that oxygen is in the 2 position in the pyran ring. The invention also includes the mouse iridoid compounds.

Abstract: A tetrapyrollic photosensitizer compound having at least one pendant —CH2CH2CON(CH2CON(CH2COOH)2)2 or —N(CH2COOH)2 group or esters thereof said tetrapyrollic compound being a chlorin, bacteriochlorin, porphyrin, pyropheophorbide, purpurinimide, or bacteriopurpurinimide. Desirably the compound has the formula: or a pharmaceutically acceptable derivative thereof, wherein R1-R8 and R10 are various substituents and R9 is substituted or unsubstituted —CH2CH2CON(CH2CON(CH2COOH)2)2; or —N(CH2COOH)2. The invention also includes a method of treatment by photodynamic therapy by treatment with light after injecting the compound and a method of imaging by fluorescence after injection of the compound.

Abstract: This invention provides nanocrystals or polymer doped nanocrystals of hydrophobic drug molecules as stably dispersed in an aqueous system which are prepared without stabilizers like surfactants and the like. In one embodiment, the drug is a tetra-pyrrole compound. An example is the hydrophobic photosensitizing anticancer drug 2-devinyl-2-(1-hexyloxyethyl)pyropheophorbide (HPPH). Pharmaceutical compositions comprising nanocrystals or polymer doped nanocrystals of hydrophobic drugs can be used for therapeutic purposes. For example pyropheophorbides such as HPPH can be used for photodynamic therapy. Drug efficacy of these nanocrystals were found to be comparable with that of same drug formulated in conventional delivery vehicles under in vitro and in vivo conditions.

Abstract: This invention describes a first report on the synthesis of certain 124I-labelled photosensitizers related to chlorines and bacteriochlorins with long wavelength absorption in the range of 660-800 nm. In preliminary studies, these compounds show a great potential for tumor detection by positron emission tomography (PET) and treatment by photodynamic therapy (PDT). The development of tumor imaging or improved photodynamic therapy agent(s) itself represent an important step, but a dual function agent (PET imaging and PDT) provides the potential for diagnostic body scan followed by targeted therapy.

Abstract: The present invention is directed to novel photosensitive compounds that can be replicated with great certainty and provide applications for photodynamic therapy.

Abstract: A method for treatment of hyperproliferative tissue which by exposing the hyperproliferative tissue to a sufficient quantity of a purified iridoid compound to inhibit its growth, where the iridoid compound includes a polysubstituted cyclopenta(c)dihydropyran where the cyclopenta ring is substituted at its 2? position with a ketofuryl group, where the numbering of the fused cyclopenta(c)dihydropyran ring structure includes heterocyclic oxygen, is counterclockwise and begins at the first carbon atom counterclockwise from the cyclopenta ring so that oxygen is in the 2 position in the pyran ring. The invention also includes the mouse iridoid compounds.

Abstract: The present invention is directed to novel photosensitive compounds that can be replicated with great certainty and provide applications for photodynamic therapy.