Abstract: The present invention generally relates to imaging and selective retention of phospholipid ether analogs in various neoplastic tissues. Specifically, the present invention relates to imaging and methods for selective retention of analogs, for example, NM404, in cancers such as Colorectal Cancer.

Abstract: A surface-modified lipoprotein-like oil-in-water emulsion useful as a blood-pool selective delivery vehicle for lipophilic imaging agents or lipophilic derivatives of water-soluble imaging agents. The blood-pool selective delivery vehicle remains in the blood for several hours, shows very little early hepatic sequestration, and is cleared from the blood within 24 hours. The mean diameter of the oil phase is less than 150 nm which minimizes sequestration by the reticuloendothelial system. The surface of the oil phase is modified with a polyethyl glycol-modified phospholipid to prevent normal interactions with the receptor sites of the hepatocytes.

Abstract: The present invention discloses boronic acids and esters of phospholipid ether analogs and methods for their synthesis and use. The boronic acids and esters of phospholipid ether analogs described herein can be used in treating cancer and in particular can be used in conjunction with radiation therapy, such as external beam radiation therapy and neutron capture therapy to specifically target and kill cancer cells.

Abstract: Disclosed are improved methods for the synthesis of phospholipid ether analogs and alkyl phosphocholine analogs. The methods allow greater versatility of the reactants used and greater ease in synthesizing alkyl chains of varying length while affording reaction temperatures at room temperature or below. The methods disclosed herein provide reactants and conditions using alkyl halides and organozinc reagents and do not utilize Gringard reactions thus, allowing greater ease of their separation and purity of products. The PLE compounds synthesized by the methods disclosed herein can also be used for synthesizing high specific activity phospholipid ether (PLE) analogs, for use in treatment and diagnosis of cancer.

Abstract: A surface-modified lipoprotein-like oil-in-water emulsion useful as a blood-pool selective delivery vehicle for lipophilic imaging agents or lipophilic derivatives of water-soluble imaging agents. The blood-pool selective delivery vehicle remains in the blood for several hours, shows very little early hepatic sequestration, and is cleared from the blood within 24 hours. The mean diameter of the oil phase is less than 150 nm which minimizes sequestration by the reticuloendothelial system. The surface of the oil phase is modified with a polyethyl glycol-modified phospholipid to prevent normal interactions with the receptor sites of the hepatocytes.

Abstract: A surface-modified lipoprotein-like oil-in-water emulsion useful as a blood-pool selective delivery vehicle for lipophilic imaging agents or lipophilic derivatives of water-soluble imaging agents. The blood-pool selective delivery vehicle remains in the blood for several hours, shows very little early hepatic sequestration, and is cleared from the blood within 24 hours. The mean diameter of the oil phase is less than 150 nm which minimizes sequestration by the reticuloendothelial system. The surface of the oil phase is modified with a polyethyl glycol-modified phospholipid to prevent normal interactions with the receptor sites of the hepatocytes.

Abstract: The present invention provides improved radioiodinated phospholipid ether analogs which demonstrate significant tumor avidity and longer plasma half-life than shorter-chain analogs. The radioiodinated phospholipid ether analogs of the present invention provide superior imaging and visualization of neoplastic lesions and tumor-specific cytotoxic cancer therapy.

Abstract: The present invention provides improved radioiodinated phospholipid ether analogs which demonstrate significant tumor avidity and longer plasma half-life than shorter-chain analogs. The radioiodinated phospholipid ether analogs of the present invention provide superior imaging and visualization of neoplastic lesions and tumor-specific cytotoxic cancer therapy.

Abstract: Improved radioiodinated phospholipid ether analogs are described which exhibit significant tumor avidity and longer plasma half-life relative to shorter chain analogs. Use of these compounds results in superior imaging and visualization of neoplastic lesions and tumor-specific cytotoxic cancer therapy.

Abstract: A heat and shelf-stable oil-in-water emulsion useful as a tissue or cell-selective delivery vehicle. Radioactive or stable, synthetic or semi-synthetic polyhalogenated triglycerides, such as 2-oleoylglycerol-1,3-bis[7-(3-amino-2,4,6-triiodophenyl)heptanoate] or 2-oleoylglycerol-1,3-bis[.omega.-(3,5-bis-trifluoromethyl)hepatanoate] or phenyl acetate, can be incorporated into the lipophilic core of a lipoprotein-like emulsion particle. The lipophilic core is surrounded by a phospholipid membrane comprising cholesterol and apolipoproteins. For hepatocyte-selective delivery, the emulsion is chylomicron remnant-like by being in a size range of 50 to 200 nm as measured by number weighting analysis with a narrow size distribution (<2% greater than 300 nm) and having a composition simulating naturally-occurring chylomicron remnants. Use of cholesterol in the emulsion formula facilitates association of apolipoproteins, especially Apo E which are recognized by liver cells and necessary for binding and uptake.

Abstract: A heat and shelf-stable oil-in-water emulsion useful as a tissue or cell-selective delivery vehicle. Radioactive or stable, synthetic or semi-synthetic polyhalogenated triglycerides, such as 2-oleoylglycerol-1,3-bis[7-(3-amino-2,4,6-triiodophenyl)heptanoate] or 2-oleoylglycerol-1,3-bis[.omega.-(3,5-bis-trifluoromethyl)-heptanoate] or phenyl acetate, can be incorporated into the lipophilic core of a lipoprotein-like emulsion particle. The lipophilic core is surrounded by a phospholipid membrane comprising cholesterol and apolipoproteins. For hepatocyte-selective delivery, the emulsion is chylomicron remnant-like by being in a size range of 50 to 200 nm as measured by number weighting analysis with a narrow size distribution (<2% greater than 300 nm) and having a composition simulating naturally-occurring chylomicron remnants. Use of cholesterol in the emulsion formula facilitates association of apolipoproteins, especially Apo E which are recognized by liver cells and necessary for binding and uptake.

Abstract: A heat and shelf-stable oil-in-water emulsion useful as a tissue or cell-selective delivery vehicle. Radioactive or stable, synthetic or semi-synthetic polyhalogenated triglycerides, such as 2-oleoylglycerol-1,3-bis[7-(3-amino-2,4,6-triiodophenyl)heptanoate] or 2-oleoylglycerol-1,3-bis[.omega.-(3,5-bis-trifluoromethyl)hepatanoate] or phenyl acetate, can be incorporated into the lipophilic core of a lipoprotein-like emulsion particle. The lipophilic core is surrounded by a phospholipid membrane comprising cholesterol and apolipoproteins. For hepatocyte-selective delivery, the emulsion is chylomicron remnant-like by being in a size range of 50 to 200 nm as measured by number weighting analysis with a narrow size distribution (<2% greater than 300 nm) and having a composition simulating naturally-occurring chylomicron remnants. Use of cholesterol in the emulsion formula facilitates association of apolipoproteins, especially Apo E which are recognized by liver cells and necessary for binding and uptake.

Abstract: A heat and shelf-stable oil-in-water emulsion useful as a tissue or cell-selective delivery vehicle. Radioactive or stable, synthetic or semi-synthetic polyhalogenated triglycerides, such as 2-oleoylglycerol-1,3-bis?7-(3-amino-2,4,6-triiodophenyl)heptanoate! or 2-oleoylglycerol-1,3-bis?.omega.-(3,5-bis-trifluoromethyl)heptanoate! or phenyl acetate, can be incorporated into the lipophilic core of a lipoprotein-like emulsion particle. The lipophilic core is surrounded by a phospholipid membrane comprising cholesterol and apolipoproteins. For hepatocyte-selective delivery, the emulsion is chylomicron remnant-like by being in a size range of 50 to 200 nm as measured by number weighting analysis with a narrow size distribution (<2% greater than 300 nm) and having a composition simulating naturally-occurring chylomicron remnants. Use of cholesterol in the emulsion formula facilitates association of apolipoproteins, especially Apo E which are recognized by liver cells and necessary for binding and uptake.

Abstract: Novel iodinated arylaliphatic triglyceride analogs as radiologic agents are liver and hepatocyte site-specific. The triglyceride backbone structure is preferably 1,3-disubstituted or 1,2,3-trisubstituted with, in some embodiments, a 3-substituted-2,4,6-triiodophenyl aliphatic chain wherein the chain has a structure similar to naturally occurring fatty acids. In another embodiment, a monoiodophenyl aliphatic chain is utilized. Any position remaining on the triglyceride backbone is substituted with a saturated or unsaturated aliphatic hydrocarbon chain of the type found in naturally occurring fatty acids. The triglyceride analogs can be radioiodinated. In a preferred embodiment, a lipid emulsion is provided as the carrier vehicle.

Abstract: Novel iodinated arylaliphatic triglyceride analogs as radiologic agents are liver and hepatocyte site-specific. The triglyceride backbone structure is preferably 1,3-disubstituted or 1,2,3-trisubstituted with, in some embodiments, a 3-substituted-2,4,6-triiodophenyl aliphatic chain wherein the chain has a structure similar to naturally occuring fatty acids. In another embodiment, a monoiodophenyl aliphatic chain is utilized. Any position remaining on the triglyceride backbone is substituted with a saturated or unsaturated aliphatic hydrocarbon chain of the type found in naturally occurring fatty acids. The triglyceride analogs can be radioiodinated. In a preferred embodiment, a lipid emulsion is provided as the carrier vehicle.

Abstract: Novel iodinated arylaliphatic triglyceride analogs, as radiologic agents are liver and hepatocyte site-specific. The triglyceride backbone structure is preferably 1,3-disubstituted or 1,2,3-trisubstituted with, in some embodiments, a 3-substituted-2,4,6-triiodophenyl aliphatic chain wherein the chain has a structure similar to naturally occurring fatty acids. In another embodiment, a monoiodophenyl aliphatic chain is utilized. Any position remaining on the triglyceride backbone is substituted with a saturated or unsaturated aliphatic hydrocarbon chain of the type found in naturally occurring fatty acids. The triglyceride analogs can be radioiodinated. In a preferred embodiment, a lipid emulsion is provided as the carrier vehicle.