Abstract: The invention relates to chelate compounds which can be used in MRI, the chelates being intended to be conveyed by lipophilic transporters, such as lipid nanoparticles or liposomes. The invention also relates to compounds comprising, in association, these chelates and these transporters, if appropriate connected via chemical bonding groups, and to their use in diagnostic imaging, it being possible for this association additionally to comprise biological targeting markers, denoted biovectors.

Abstract: The present invention relates to a method of imaging of an animate human or non-human animal body, which method comprises: administering parenterally to said body a particulate material comprising a matrix or membrane material and at least one contrast generating species, which matrix or membrane material is responsive to a pre-selected physiological parameter whereby to alter the contrast efficacy of said species in response to a change in the value of said parameter; generating image data of at least part of said body in which said species is present; and generating therefrom a signal indicative of the value or variation of said parameter in said part of said body. The invention also relates to contrast media for imaging a physiological parameter.

Abstract: A pharmaceutical preparation containing magnetic vesicular particles is disclosed, wherein the magnetic vesicular particles each include magnetic microparticles within a lipid membrane, an organic compound having at least two groups selected from the group consisting of a hydroxyl group, a carboxyl group, a carbamoyl group, an amino group, a mercapto group, a sulfo group, a dithio group, a thiocarboxyl group and a dithiocarboxyl group is bonded to the magnetic microparticle, and the magnetic vesicular particles satisfy the following equation: 0.05?R/(r×100)?1.5 wherein R represents an average grain size of the magnetic vesicular particles and r represents an average particle size of magnetic microparticles included in the magnetic vesicular particles.

Abstract: A chemical exchange saturation transfer (CEST) contrast agent is provided. One embodiment includes a ligand and a functional group linked to the ligand. The functional group has a hydrogen exchange site and is capable of undergoing a change in chemical functionality by enzyme catalysis or reaction with a metabolite to change the chemical exchange rate or the MR frequency of the hydrogen exchange site.

Abstract: The present invention relates to a method for the in vivo, ex vivo, or in vitro determination of physical or chemical parameters of diagnostic interest by use of a slow tumbling paramagnetic agent that is responsive to changes of said physical or chemical parameter through changes in the R2p/R1p ratio allowing the determination of the said parameter in a manner that is independent on the actual agent concentration.

Abstract: An agent for the transfer of genetic material comprising a genetic material, PEG-containing liposomes, one or more additional polymer particles and a contrasting agent. The invention also is directed toward methods of preparing the agent, and methods of using the agent to affect gene transfer.

Abstract: A pharmaceutical preparation containing magnetic vesicular particles is disclosed, wherein the magnetic vesicular particles each include magnetic microparticles within a lipid membrane, an organic compound having at least two groups selected from the group consisting of a hydroxyl group, a carboxyl group, a carbamoyl group, an amino group, a mercapto group, a sulfo group, a dithio group, a thiocarboxyl group and a dithiocarboxyl group is bonded to the magnetic microparticle, and the magnetic vesicular particles satisfy the following equation: 0.05?R/(r×100)?1.5 wherein R represents an average grain size of the magnetic vesicular particles and r represents an average particle size of magnetic microparticles included in the magnetic vesicular particles.

Abstract: The present invention relates to a method for making a test device for detecting or quantifying an analyte in a sample. This method involves contacting a membrane with a mixture including derivatized, marker-loaded liposomes, and substantially dehydrating the mixture on the membrane under vacuum pressure at a temperature of from about 4° C. to about 80° C., wherein said mixture further includes one or more sugars in an amount sufficient to promote the stability of the liposomes during dehydration and rehydration. The present invention also relates to a test device and method for detecting or quantifying an analyte in a sample. The test device includes a membrane which includes an immobilized liposome zone, wherein the immobilized liposome zone has bound thereto dehydrated, derivatized, marker-loaded liposomes dehydrated under vacuum pressure at a temperature of from about 4° C. to about 80° C.

Abstract: The invention describes SAGE (sdph3.10) and sdp3.5 tumor associated nucleic acids, including fragments and biologically functional variants thereof. Also included are polypeptides and fragments thereof encoded by such nucleic acid molecules, and antibodies relating thereto. Methods and products also are provided for diagnosing and treating conditions characterized by expression of a sdph3.10 and/or sdp3.5 gene product.

Abstract: The invention provides compositions and methods for non-invasive imaging of enzyme (e.g., protease) activity in cells, tissues and organs and entire bodies in vitro, in vivo and in situ. The invention provides a chimeric polypeptide having a bioluminescent or chemiluminescent polypeptide, or a heterologous kinase, and at least one silencing moiety, and a protease cleavage motif positioned between the first and second domains. The imaging can be by computer assisted tomography (CAT), magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), or bioluminescence imaging (BLI).

Abstract: Disclosed is a new structural class of amphiphilic molecules which incorporate a hydrophilic material or polymer attached, at spatially distinct sites, to at least two hydrophobic residues. Certain of the amphiphilic molecules comprise a plurality of hydrophobic moieties. All such amphiphilic molecules have a common structural motif and, in contact with water, display surface activity and self-assemble into multimolecular aggregates and liquid crystalline phases. Also disclosed are enhanced stability liposomes that incorporate such amphiphilic molecules via unique interactions, and methods of using such formulations in a variety of applications including drug delivery, nutrition, bio-diagnostics, cosmetics, blood products and related applications.

Abstract: Bioelastomers are disclosed for use in methods of binding compounds including immunoassay methods, in biosensors and methods or regenerating biosensors, and in methods for targeting the delivery of a compound to a particular location within an animal subjects. In general, the bioelastomer is conjugated to a binding compound, which is in turn used to bind a compound of interest. For targeted compound delivery, the bioelastomer is conjugated to the compound to be delivered.

Abstract: Emulsions preferably of nanoparticles formed from high boiling liquid perfluorochemical substances, said particles coated with a lipid/surfactant coating are made specific to regions of activated endothelial cells by coupling said nanoparticles to a ligand specific for ?v?3 integrin, other than an antibody. The nanoparticles may further include biologically active agents, radionuclides, or other imaging agents.

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 intravascular thrombi.

Abstract: An anti-cancer composition having biocompatible materials, which can selectively exploit chemical variations between normal cells and cancer cells to inhibit or prevent the proliferation of cancerous cells and methods of use.

Abstract: The present invention concerns a contrast agent compound for CEST imaging wherein said contrast agent comprises a proton pool encapsulating system that contains a pool of water mobile shifted protons.

Abstract: The present invention relates to nanoparticle vaccines comprised of a carrier, particularly polymerized lipids, having multiple copies of an antigen or combinations of different antigens displayed on the carrier. Such antigen-displaying nanoparticles may also display a targeting molecule on its surface in order to direct it to a specific site or cell type to optimize a desired immune response. The present invention also relates to encapsulating an antigen or combinations of different antigens within such nanoparticles, with or without a targeting molecule displayed on its surface. The antigens used in this invention are effective to produce an immune response against a variety of pathological conditions.

Abstract: Composition for diagnostic or therapeutic use which comprises an assembly comprising an active agent. The assembly comprises a liposome and a plurality of micellar components associated thereto, said micellar components being associated to the outer surface of the envelope of said liposome through a substantially electrostatic interaction. When an active compound is incorporated into the micelles, a substantial amount of said active compound can be linked to a singe liposome. Furthermore, the presence of the outer micellar layer allows to increase the residence time of said liposome in the blood stream.

Abstract: A liposome containing a hydrophobic chelate compound as a membrane component, and an MRI contrast medium containing the liposome for use in imaging of, preferably, a vascular disease. An MRI contrast medium that accumulates in a lesion of a vascular disease caused by abnormal proliferation of vascular smooth muscle cells such as arteriosclerosis is provided.

Abstract: Emulsions preferably of nanoparticles formed from high boiling liquid perfluorochemical substances, said particles coated with a lipid/surfactant coating are made specific to regions of activated endothelial cells by coupling said nanoparticles to a ligand specific for ?v?3 integrin, other than an antibody. The nanoparticles may further include biologically active agents, radionuclides, or other imaging agents.

Abstract: Provided are a functionalized, encapsulated fluorescent nanocrystal comprising a liposome having encapsulated therein one or more fluorescent nanocrystals; use of the functionalized, encapsulated fluorescent nanocrystals in detection systems; and a method of producing functionalized, encapsulated fluorescent nanocrystals. A method of using the functionalized encapsulated fluorescent nanocrystals having affinity molecule bound thereto comprises contacting the functionalized encapsulated fluorescent nanocrystals with a sample so that complexes are formed between the functionalized encapsulated fluorescent nanocrystals and substrate for which the affinity molecule has binding specificity, if the substrate is present; exposing the complexes in the detection system to an excitation light source, and detecting a fluorescence peak emitted from the complexes, if present.

Abstract: The present invention is directed, in part, to compounds and methods for diagnostic imaging, comprising administering to a patient a contrast agent which has an overall negative charge.

Abstract: To provide a screening method for an apoptosis-suppressing substance or an apoptosis-promoting substance, the application of which substances to pharmaceuticals or diagnostic drugs are expected, also to provide an apoptosis-suppressing substance or an apoptosis-promoting substance, since Bcl-2 family having apoptosis-suppressing or -promoting activities is deeply involved in many diseases. To attain the above object, VDAC-liposomes, an indicator substance such as fluorescent-labeled cytochrome c or isotope-labeled sucrose etc. capable of passing through VDAC (voltage-dependent anion channel), and a subject substance are incubated, and then concentration changes in the indicator substance, inside and outside the VDAC-liposomes before and after the incubation, are detected in order to estimate presence or absence of the apoptosis-suppressing activity or -promoting activity of the subject substance.

Abstract: The present invention provides biocompatible vesicles comprising semi-permeable, thin-walled encapsulating membranes which are formed in an aqueous solution, and which comprise one or more synthetic super-amphiphilic molecules. When at least one super-amphiphile molecule is a block copolymer, the resulting synthetic vesicle is termed a “polymersome.” The synthetic, reactive nature of the amphiphilic composition enables extensive, covalent cross-linking of the membrane, while maintaining semi-permeability. Cross-linking of the polymer building-block components provides mechanical control and long-term stability to the vesicle, thereby also providing a means of controlling the encapsulation or release of materials from the vesicle by modifying the composition of the membrane. Thus, the encapsulating membranes of the present invention are particularly suited for the reliable, durable and controlled transport, delivery and storage of materials.

Abstract: Methods and devices for enhanced ultrasound detection based upon changing temperature and ultrasound reflectivity of a temperature-dependent contrast agent bound to an ultrasound target are disclosed. The methods and devices can be used for enhanced imaging alone or in conjunction with drug delivery, with therapeutic approaches such as hyperthermia or cryotherapy or with other imaging modalities.

Abstract: Disclosed are CEST paramagnetic agents comprising a substrate (SH) containing mobile protons bonded to a para-magnetic chelate (SR) containing a metal selected from iron (11) (high-spin configuration), iron (111), cobalt (11), rhodium (11), copper (11), nickel (11), cerium (111), praseodymium (111), neodymium (111), dysprosium (111), erbium (111), terbium (111), holmium (111), thulium (III), ytterbium (III) and europium (111).

Abstract: The present invention is directed to a lipid-based delivery system for administration of an active drug substance selected from lysolipid derivatives which are particularly useful in the treatment or detection of parasitic infections, especially parasitic infections which cause an elevated PLA2 level in the infected mammal. Preferred parasitic infections are infections wherein the life cycle of the parasite involves the liver and/or spleen of the infected organism.

Abstract: A liposomal composition and a method of using the same for achieving intracellular delivery of a liposome-entrapped agent is described. The liposomes are composed of a pH sensitive lipid and include a targeting ligand to direct the liposomes to a target cell. The liposomes also include a stabilizing component, such a polymer-derivatized lipid, where the polymer is attached to the lipid by a releasable linkage. Administration of the liposomes results in cellular internalization and destabilization of the liposome for intracellular delivery of the entrapped agent.

Abstract: Angiogenic endothelial cells are selectively targeted with lipid/DNA complexes or cationic liposomes containing a substance which affects the targeted cells by inhibiting or promoting their growth. A site of angiogenesis can be precisely located by administering cationic liposomes containing a detectable label. The complexes may comprise nucleotide constructs which are comprised of promoters which are selectively and exclusively activated in the environment of an angiogenic endothelial cell.

Abstract: The present invention provides a sugar-modified liposome having a sugar chain bonded to its membrane surface, preferably through a linker protein, and having excellent absorption qualities, particularly in the intestine. The molecular structure and quantity of the sugar chain is selectively varied to allow the liposome to be delivered in a targeted manner to selected cells and tissues. The liposome is applicable to medicinal drugs, cosmetics and other various products in the medical/pharmaceutical fields, and it is especially useful in a therapeutic drug delivery system that recognizes target cells and tissues, such as cancer cells, and in the delivery of drugs or genes locally to a selected region, or in a diagnostic cell/tissue sensing probe.

Abstract: Provided are a functionalized, encapsulated fluorescent nanocrystal comprising a liposome having encapsulated therein one or more fluorescent nanocrystals; use of the functionalized, encapsulated fluorescent nanocrystals in detection systems; and a method of producing functionalized, encapsulated fluorescent nanocrystals. A method of using the functionalized encapsulated fluorescent nanocrystals having affinity molecule bound thereto comprises contacting the functionalized encapsulated fluorescent nanocrystals with a sample so that complexes are formed between the functionalized encapsulated fluorescent nanocrystals and substrate for which the affinity molecule has binding specificity, if the substrate is present; exposing the complexes in the detection system to an excitation light source, and detecting a fluorescence peak emitted from the complexes, if present.

Abstract: A liposome including a fusogenic liposome, a linking moiety and a targeting moiety. The fusogenic liposome is a lipid bilayer encapsulating contents. The linking moiety is electrostatically bound to the lipid bilayer, and the targeting moiety is covalently bound to the linking moiety. The liposome may also include a stabilizing moiety interposed between the linking and targeting moieties, and covalently bound to both. Alternatively, the stabilizing and targeting moieties may be covalently bound to separate linking moieties, the linking moieties being electrostatically bound to the lipid bilayer.

Abstract: Magnetic nanoparticles are applicable in imaging, diagnosis, therapy, and biomaterial separation. The magnetic nanoparticles are represented as (FewGdx)Zy, wherein w is from 99.9% to 97.5%, x is from 0.1% to 2.5%, Z is an element of the group VIa, and v, y are positive numbers.

Abstract: New intracorporeal radiodense medicaments and certain medical uses and methods for use of such high energy phototherapeutic medicaments for treatment of human or animal tissue are described, wherein a primary active component of such medicaments is a halogenated xanthene or halogenated xanthene derivative. The halogenated xanthenes constitute a family of potent radiosensitizers that become photoactivated upon irradiation of the treatment site with ionizing radiation.

Abstract: The present invention provides a liposomal composition for targeted delivery of drugs. The composition comprises poloxamer molecules and liposomes encapsulating one or more delivery agents. At above the critical micellar temperature of the poloxamer, a fraction of the poloxamer molecules form micelles and another fraction becomes incorporated into the liposome surface, thereby inhibiting their adhesion to cells. At a temperature below the critical micellar temperature, the poloxamer molecules dissociate into monomers allowing the liposomes to adhere to adjacent cells and effecting retention of the liposomes in the surrounding tissue. A method is provided for delivery of agents to target site comprising administering the composition to an individual and cooling the target site to cause retention of the liposomes at or near the target site.

Abstract: The present invention relates to a radiation sensitive liposome, and the use of this liposome as carrier for therapeutic and diagnostic agent(s). In particular, the invention encompasses a liposomal delivery system, comprising a stable liposome-forming lipid and a polymerizable colipid, a fraction of which polymerizable colipid polymerizes upon exposure to ionizing radiation, thereby destabilizing the liposomal membrane. Destabilization of liposomes allows for leakage of liposomal contents. The present invention further contemplates methods of diagnosing and treating conditions and diseases that are responsive to liposome-encapsulated or associated agents.

Abstract: The present invention relates generally to the amphiphilic polyelectrolyte, poly(2-ethylacrylic acid) and covalently bonded lipids to generate Lipo-PEAA. These Lipo-PEAA are then used to make pH-sensitive liposomes which become unstable, permeable or fusogenic with certain pH changes. In addition, this invention generally describes methods for delivering therapeutic compounds and drugs to target cells by administering to a host the pH-sensitive liposomes of the present invention.

Abstract: A novel amphiphilic lipid compound having a cleavable, vinyl ether linked hydrophilic headgroup is described. Also described are liposomes containing the vinyl ether lipid compound, which may be triggered to release their contents and/or permeablize or fuse with target lipid membranes. The cleavable vinyl ether linkage allows the hydrophilic headgroup to be dissociated from the hydrophobic tailgroup(s) of the lipid compound to facilitate phase transitions in the lipid bilayer.

Abstract: A lipid represented by the formula: wherein each of R1 and R2 is an alkyl or alkenyl chain having between about 8 to about 24 carbon atoms; n=0–20; L is selected from the group consisting of (i) —X—(C?O)—Y—, (ii) —X—(C?O)—, and (iii) —X—CH2—, wherein X and Y are independently selected from oxygen, NH, and a direct bond; and Z is a weakly basic moiety that has a pK of less than about 7.4 and greater than about 4.0 is described.

Abstract: A liposome suspension forms spontaneously upon adding a lipid composition to an aqueous solution. The liposomes include diacylglycerol-PEG compounds. The melting point of the diacylglycerol-PEG is below about 40 degrees C., and the acyl chains of the diacylglycerol-PEG are greater than or equal to 14 carbons in length. Such liposome suspensions are useful for a variety of purposes, including the delivery of therapeutic agents.

Abstract: Vesicles made from amphiphilic copolymers are disclosed. The amphiphilic copolymers can be ABA copolymers, where one of A and B is hydrophilic and the other is hydrophobic. AB copolymers can also be used. The copolymers may be crosslinked to form nanocapsules. Crosslinking can be accomplished using a variety of methods, including end to end polymerization of copolymers having terminal unsaturated groups. Molecules, such as membrane proteins, can be incorporated into the wall of the vesicles or nanocapsules.

Abstract: The present invention provides for the development of endocytosis-sensitive probes, and a remote method for measuring cellular endocytosis. These probes are based on the reduced water permeability of a nanoparticle or liposomal delivery system, and inherent degradability or disruption of barrier integrity upon endocytosis. The invention also provides for liposomes having combined therapeutic and diagnostic utilities by co-encapsulating ionically coupled diagnostic and therapeutic agents, in one embodiment, by a method using anionic chelators to prepare electrochemical gradients for loading of amphipathic therapeutic bases into liposomes already encapsulating an imaging agent. The invention provides for imaging of therapeutic liposomes by inserting a lipopolymer anchored, remotely sensing reporter molecules into liposomal lipid layer. The invention allows for an integrated delivery system capable of imaging molecular fingerprints in diseased tissues, treatment, and treatment monitoring.

Abstract: Improved methods for providing an image of an internal region of a patient, especially the cardiovascular region. Embodiments of the invention involve the administration to the patient of a contrast agent which comprises a vesicle composition comprising lipid or polymer vesicles and a gas or gaseous precursor, in combination with a coronary vasodilator. The patient is scanned using diagnostic imaging, such as ultrasound, to obtain a visible image of the region. The methods are particularly useful for diagnosing the presence of diseased tissue in the cardiovascular region of a patient, as well as for measuring blood flow in the cardiovascular region of a patient.

Abstract: Novel targeted compositions which may be used for diagnostic and therapeutic use. The compositions can be used in conjunction with diagnostic imaging, such as ultrasound, as well as therapeutic applications, such as therapeutic ultrasound.

Abstract: The present invention provides biocompatible vesicles comprising semi-permeable, thin-walled encapsulating membranes which are formed in an aqueous solution, and which comprise one or more synthetic super-amphiphilic molecules. When at least one super-amphiphile molecule is a block copolymer, the resulting synthetic vesicle is termed a “polymersome.” The synthetic, reactive nature of the amphiphilic composition enables extensive, covalent cross-linking of the membrane, while maintaining semi-permeability. Cross-linking of the polymer building-block components provides mechanical control and long-term stability to the vesicle, thereby also providing a means of controlling the encapsulation or release of materials from the vesicle by modifying the composition of the membrane. Thus, the encapsulating membranes of the present invention are particularly suited for the reliable, durable and controlled transport, delivery and storage of materials.

Abstract: A method for administering a radiosensitizer to a tumor site in a subject is described. The method includes preparing liposomes composed of a vesicle-forming lipid and a lipid-derivatized radiosensitizer. In one embodiment, the radiosensitizer is dipalmitoyl-5-iodo-2′-deoxyuridine. A method for preparing the liposome composition including the lipid-derivatized radiosensitizer is also disclosed.

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: Liposomes of a specific bilayer composition containing an entrapped modifying compound are claimed. The liposomes of the invention are suitable for the internalisation of a variety of materials, even following long-term storage. Suitable materials of the invention include radiometals, parmagnetic compounds, radioopaque compounds and prodrugs. Upon internalisation, the material reacts chemically with the entrapped modifying compound such that said material remains internalised within the liposomes of the invention. Also claimed in the present invention are the liposomes containing internalised material and kits for their preparation. Furthermore, the use of said liposomes containing internalised material for the imaging infection, inflammation or tumour in a human is claimed.

Abstract: The present invention provides transition metal complexes of N,N′,N″-trialkyl-cis,cis-1,3,5-triaminocyclohexane and related compositions and methods of synthesis and use in vitro and in vivo, such as a therapeutic agent or a delivery/imaging agent.

Abstract: Provided are a functionalized, encapsulated fluorescent nanocrystal comprising a liposome having encapsulated therein one or more fluorescent nanocrystals; use of the functionalized, encapsulated fluorescent nanocrystals in detection systems; and a method of producing functionalized, encapsulated fluorescent nanocrystals. A method of using the functionalized encapsulated fluorescent nanocrystals having affinity molecule bound thereto comprises contacting the functionalized encapsulated fluorescent nanocrystals with a sample so that complexes are formed between the functionalized encapsulated fluorescent nanocrystals and substrate for which the affinity molecule has binding specificity, if the substrate is present; exposing the complexes in the detection system to an excitation light source, and detecting a fluorescence peak emitted from the complexes, if present.