Abstract: 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.

Abstract: The present invention provides tetra-amine chelator conjugates with biological targeting moieties, linked via a linker group and technetium complexes thereof as radiopharmaceuticals. The linker group is such that the chelator is mono-functionalized at the bridgehead position and provides both flexibility and a lack or aryl groups, to minimize lipophilicity and steric hulk. Protected versions of the chelators are provided which permit conjugation with a wide range of targeting molecules without interfering reactions with the amine nitrogens of the tetra-amine chelator. Syntheses of the functionalised chelators are described, together with bifunctional chelate precursors. Radiopharmaceutical compositions comprising the technetium metal complexes of the invention are described, together with non-radioactive kits for the preparation of such radiopharmaceuticals.

Abstract: The present invention is directed to arginase inhibitor compounds of formula IA or formula IB: or a pharmaceutically acceptable salt thereof, compositions containing these compounds, and methods of their use for the treatment and diagnosis of conditions characterized by upregulation of arginase, abnormally high arginase activity, or by abnormally low nitric oxide synthase activity.

Abstract: The present invention provides conjugate compounds comprising (a) an active compound; (b) optionally, but in some embodiments preferably, an affinity binding agent; and (c) a block copolymer, the block copolymer comprising: (i) a first elastin-like polypeptide having a first Tt and (U) a second elastin-like polypeptide having a second Tt greater than the first Tt. Method for the targeted delivering of an active compound in vivo to a selected region within a subject with such agents are also described.

Abstract: A pharmaceutical of the general formula Z—(L)n-V, wherein V denotes an amino acid sequence X1-X2-Val-Tyr-Ile-His-Pro-X8-X9-X10; L denotes a bond or a linker; Z denotes a group that optionally can carry an imaging moiety M; X1 denotes an amino acid; X2 denotes Arg or N-alkylated Arg or a mimetic of Arg; X8, X9 and X10 constitute an ACE cleavage site; Z forms a bond with the amino acid X1 optionally through the linker L; and M where denotes an imageable moiety capable of detection either directly or indirectly in a diagnostic imaging procedure.

Abstract: Complexes of heterocyclic radionuclides are prepared based upon ligands having substituted pyridyl and imidazolyl groups. The ligands are bifunctional, having amino acid residues that may act as a linker to a bioactive molecule, and a tridentate chelator that may complex the radionuclide. The bioactive molecule may be a peptide or somatostatin.

Abstract: A radioactive mixture and a manufacturing method thereof are disclosed. The radioactive mixture (188Re-MN/Lipiodol mixture) is formed by chelating reaction of MN series compounds that are amine-amide-disulfide amine quadric-dentate chelate ligands with TcO4?/or ReO4?, and then dissolved in Lipiodol. Moreover, the 99mTc/or 188Re of the TcO4?/or ReO4? avoids bone marrow injuries caused by free 90Y. By the feature of the Lipiodol that stays in liver tumors for a long period, the radioactive mixture is applied to treat liver cancers by injection so that injuries caused by surgical operations can be prevented. 188Re-MN/Lipiodol is used for liver cancer, breast cancer or other solid tumors treatment. Re-188 MN or Re-188 MN/Lipiodol can be mixed with anticancer drugs, hydrogel, liposome, micelle or other nano-particles to form the multifunctional therapeutic modality.

Abstract: A compound that recognizes and binds to the CA-IX protein has Formula I, II, III, or IV. The compounds may include a radioactive element for radioimaging or therapeutic applications. Thus, pharmaceutical compositions may be prepared with one or more of the compounds of Formula I, II, III, or IV.

Abstract: A compound of Formula I, a pharmaceutically acceptable salt, or solvate thereof: complexes with metals such as rhenium, technetium, and others to provide a complex for imaging tissues or treating disease, particularly where the metal is radioactive. Such complexes are specific to PSMA protein and can therefore be used in imaging or treating cancer of the prostate and other tissue where the protein is expressed.

Abstract: The present invention relates to particular radiolabeled Cannabinoid-1 (CB1) receptor modulators, and methods of using these modulators for labeling and diagnostic imaging of Cannabinoid-1 receptors in mammals, particularly humans. In addition, intermediates useful for the synthesis of the radiolabeled Cannabinoid-1 receptor modulators are also disclosed, as well as the processes for synthesizing the radiolabeled Cannabinoid-1 receptor modulators. Still further, formulations of the radiolabeled Cannabinoid-1 receptor compounds are described.

Abstract: Neurophysiologic information such as quantitative electroencephalography (QEEG) is used in a method for classifying, diagnosing, and treating physiologic brain imbalances. Neurophysiologic information is also used to guide sample selection in clinical tests for psychopharmacologic drug candidates. Finally, neurophysiologic information is used for remotely assessing and treating patients with physiologic brain imbalances.

Abstract: Disclosed here is a method for measuring the kinetics (i.e., the molecular flux rates—synthesis and breakdown or removal rates) of a plurality of proteins or organic metabolites inn living systems. The methods may be accomplished in a high-throughput, large-scale automated manner, by using existing mass spectrometric profiling techniques and art well known in the fields of static proteomics and static organeomics, without the need for additional biochemical preparative steps or analytic/instrumental devices.

Abstract: The present invention provides a radiotherapeutic composition comprising a high specific activity tin-117m source of radiotherapeutic atomic electrons and a delivery vehicle, e.g., a chelator or nanosphere or microsphere effective to contain tin-117m therein. The present invention also provides a targeting moiety linked to the delivery vehicle. Further provided are methods of treating a bone-associated pathophysiological condition or imaging the same using the high specific activity radiotherapeutic compositions.

Abstract: The present invention refers to diagnostically or radiotherapeutically useful compounds which are able to selectively bind to lectins, having formula (I) wherein R, R?, R1, R2 and R3 are as defined in the specification; the process for their preparation and the pharmaceutical compositions thereof.

Abstract: Degradable macromolecular magnetic resonance imaging contrast agents for use in various diagnostic procedures, and methods for synthesizing, using and degrading these agents, are described. The macromolecule contrast agents disclosed in various aspects of this invention are degradable gadolinium compounds which show prolonged plasma retention, and enhanced permeability and retention in solid tumors, but are still capable of being rapidly cleared from the body.

Abstract: The present invention is directed to a method for preparing an anhydrous 18F-radiolabeled fluorinating agent by a nucleophilic reaction of a hydrated 18F-radiolabeled fluoride ion source with an unsaturated carrier compound; treating the 18F-radiolabeled carrier compound to produce a non-aqueous mixture of the 18F-radiolabeled carrier compound in a solvent; and reacting the 18F-radiolabeled carrier compound with a nucleophilic composition in a nucleophilic reaction to produce an anhydrous 18F-radiolabeled fluorinating agent. The present invention is also directed to an anhydrous 18F-radiolabeled fluorinating agent comprising the formula [QnM]x+(18F?)x. Additionally, the present invention is directed to an 18F-radiolabeled fluorinated radiopharmaceutical or an 18F-radiolabeled fluorinated radiotracer prepared by reacting the anhydrous 18F-radiolabeled fluorinating agent with a drug intermediate.

Abstract: Compounds having formula I, or pharmaceutically acceptable salts, hydrates or N-oxides thereof are provided and are useful for binding to CXCR7, and treating diseases that are dependent, at least in part, on CXCR7 activity. Accordingly, the present invention provides in further aspects, compositions containing one or more of the above-noted compounds in admixture with a pharmaceutically acceptable excipient.

Abstract: The present invention relates to biodegradable biocompatible polyketals, methods for their preparation, and methods for treating animals by administration of biodegradable biocompatible polyketals. In one aspect, a method for forming the biodegradable biocompatible polyketals comprises combining a glycol-specific oxidizing agent with a polysaccharide to form an aldehyde intermediate, which is combined with a reducing agent to form the biodegradable biocompatible polyketal. The resultant biodegradable biocompatible polyketals can be chemically modified to incorporate additional hydrophilic moieties. A method for treating animals includes the administration of the biodegradable biocompatible polyketal in which biologically active compounds or diagnostic labels can be disposed. The present invention also relates to chiral polyketals, methods for their preparation, and methods for use in chromatographic applications, specifically in chiral separations.

Abstract: The present invention provides compounds and amyloid probes thereof that allow for an antemortem method of diagnosing AD and quantitating the extent or progression of amyloid deposits (plaques) by in vivo imaging of amyloid and/or amyloid deposits in the regions of the brain. Preferably, an amyloid probe of the invention can cross the blood-brain barrier and distinguish AD brain from normal brain. An amyloid probe can be administered to a patient in amounts suitable for in vivo imaging of amyloid deposits. Amyloid probes of the invention can also be used to detect and quantitate amyloid deposits in diseases including, without limitation, Down's syndrome, familial AD and homozygotes for the apolipoprotein E4 allele. In one aspect, the compounds may be used in the treatment or prophylaxis of diseases that include, without limitation, AD and type 2 diabetes mellitus.

Abstract: Photochemical demethylation reactions in solutions of thiazine dyes, in which the dye molecules act as both sensitizer and substrate, are reduced by quenching triple-state dye molecules, returning them to the unreactive ground state.

Abstract: A method of diagnosing attention deficient-hyperactivity disorder (ADHD) in a human patient by assessing the level of dopamine transporter in at least one region of the patient's central nervous system, where an elevated level of dopamine transporter in the patient is indicative of ADHD. In embodiments of the invention, assessment of dopamine transporter levels includes assessing binding of a dopamine transporter ligand to the dopamine transporters using PET or SPECT.

Abstract: The present invention is directed towards novel folate-conjugates of formula I wherein F is a folate or derivative thereof, Z1, Z2, Z3 are independently of each other C or N, S1 to S4 are independently of each other a single bond or a spacer, Ra, Ra?, and Rb are donor groups and/or another group F, Rc is optionally another group F and n is 1 or 2. The invention further contemplates the corresponding metal-chelate complexes as well as pharmaceutical compositions thereof, and their uses in diagnostic imaging and radiotherapy.

Abstract: A method for cardiac imaging is provided, including administering to an adult human subject an amount of a teboroxime species having a radioactivity of less than 5 mCi at a time of administration, and performing a SPECT imaging procedure of a cardiac region of interest (ROI) of the subject. Other embodiments are also described.

Abstract: A dendritic compound of the following structure: PDn-Z-L is disclosed. In the structure above, P is X—(CH2CH2—O)r—, r is an integer ranging from 1000 to 4000, X is OH, NH2, or OR, R is C1 to C10alkyl, Dn is a residue of branched C3 to C30 polyol compounds, n is the quantity of layers of the residue of branched compounds and is an integer equal to or greater than 1, L is a metal cation, Z is the residue of a C3 to C30 compound with multi functional groups. The functional groups illustrated above can be carboxylic groups, amino groups, amide groups, or chelating groups. The carboxylic groups, ester groups, amino groups, or amide groups bind to Dn, and the chelating groups bind to the metal cations.

Abstract: Provided are radiolytically and metabolically stable metal complexes based on tetrathiol ligands useful for nuclear medical diagnostics and in endoradionuclide therapy. Methods for their preparation are also provided. The complexes can have a central ligand, Y, that can be 99mTcO, 186ReO, 188ReO, 99mTcN, 186ReN or 188ReN.

Abstract: Radiolabeled tracers for sulfotransferases (SULTs), their synthesis, and their use are provided. Included are substituted phenols, naphthols, coumarins, and flavones radiolabeled with 18F, 123I, 124I, 125I, or 11C. Also provided are in vivo techniques for using these and other tracers as analytical and diagnostic tools to study sulfotransferase distribution and activity, in health and disease, and to evaluate therapeutic interventions.

Abstract: Provided herein are agents that bind to soluble beta-amyloid. Also provided are in vivo and in vitro methods for detecting soluble beta-amyloid in a sample that may include brain tissue.

Abstract: The present invention provides hydroxypyridinone and hydroxypyrimidone chelating agents. Also provides are Gd(III) complexes of these agents, which are useful as contrast enhancing agents for magnetic resonance imaging. The invention also provides methods of preparing the compounds of the invention, as well as methods of using the compounds in magnetic resonance imaging applications.

Abstract: The invention, in one aspect, relates to radiolabeled compounds. The invention also relates to radiolabeled liposomes and methods of making and using thereof. The invention also relates to kits for preparing radiolabeled liposomes.

Abstract: An organized mobile multicomponent conjugate (OMMC) and method of using to enhance binding of weakly binding compounds to a target. A lamellar structure containing at least two binding compounds is assembled under conditions in which the binding compounds self-regulate in or on the lamellar structure, forming a cooperative ensemble that is capable of binding with enhanced affinity to a complementary affinity site on a target. Each binding compound is bound to the lamellar surface, and may be connected by a linker. The OMMC may contain an effector molecule, such as a diagnostic or therapeutic agent, for administration to a patent who is then diagnosed or treated using the effector molecule.

Abstract: A method for visualizing biological material, preferably by MRI, comprising the steps of: (i) bringing a population of coated nanoparticles into contact with said biological material, each of which nanoparticles comprises a) a metal oxide of a transition metal, said metal oxide preferably being paramagnetic and preferably comprising a lanthanide (+III) such as gadolinium (+III), and b) a coating covering the surface of the core particle, and (ii) recording the image; wherein the coating is hydrophilic and comprises a silane layer which is located next to the surface of the core particle and comprises one or more different silane groups which each comprises an organic group R and a silane-siloxane linkage where a) R comprises a hydrophilic organic group R? and a hydrophobic spacer B, b) O is oxygen directly binding to a surface metal ion of the metal oxide, and c) C is carbon and is also part of B.

Abstract: The present invention provides conjugates useful for the diagnosis and treatment of diseases associated with the over-expression of COX-2. The conjugates comprise a selective COX-2 targeting carrier, a metal coordinating moiety, and a linker chemically linking the metal coordinating moiety to the carrier. The metals coordinated by the metal coordinating moiety are selected from paramagnetic or radioisotopes. The invention also includes kits comprising a conjugate and a radioisotope solution.

Abstract: This invention provides methods of using Rhenium radioisotopes to detect and treat tumors that express a Na+/I? symporter. The invention also provides compositions and methods of making compositions comprising Rhenium radioisotopes for detection and treatment of tumors that express a Na+/I? symporter.

Abstract: The invention relates to dendritic chelated compounds, to methods for producing the same and to pharmaceutical compositions containing the same. The dendritic chelated complexes of the present invention have the following formula (I): [[MC]En-[D]m—X1p1X2p2X3p3X4p4]z? z B+ (I), where m is a magnetic or scintigraphic marker, C is a chelating agent of the marker M, E is a spacer, n=0 or 1, D is compound capable of forming a dendritic structure, m is an integer equal to 1 or 2 or 4, X1 is a group increasing the complex lipophily, p1 is an integer from 0 to 12, X2 is a group increasing the complex specificity for a particular organ, p2 is an integer equal to 1 or 2 or 4, X3 is a group having a therapeutic activity, p3 is an integer equal to 0, 1, 2 or 4, X4 is a CH3 group, p4 is an integer from 0 to 12, B is a counter-ion, z is an integer equal to 0, 1, 2, 3 or 4. The invention can be used in the field of pharmacy, more precisely in medical imaging.

Abstract: Disclosed herein are non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a phenazine or quinoxaline substituent. Also disclosed herein are non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such polypeptides.

Abstract: There are described Compounds of formula (I) in which R3 to R8 are independently selected from hydrogen, halogen, trihaloalkyl, alkyl having 1, 2, 3, 4 or 5 carbon atoms, electron donor groups selected from alkoxy having 1, 2, 3, 4 or 5 carbon atoms, trihaloalkoxy, hydroxy or amino, electron acceptor groups selected from cyano, sulphonic, nitro, or amide; R1 is an optionally substituted phenyl, benzyl or cyclohexyl group; R2 is selected from amino, substituted amino or guanidino groups, Z is a saturated or unsaturated C1-5 hydrocarbon chain, and salts thereof. A process for their preparation and compositions containing them are also described. The Compounds are either agonists or antagonists of a specific adenosine receptor or a number of adenosine receptors and have usefulness for the treatment of inflammation, arthritic conditions, rheumatoid arthritis, Osteoarthritis, mental disorders, or for inducing central nerve regeneration.

Abstract: Novel radiopharmaceuticals that are useful in diagnostic imaging and therapeutic treatment of disease characterized by overexpression of seprase include complexes that contains a proline moiety and a radionuclide adapted for radioimaging and/or radiotherapy:

Abstract: The present invention relates to novel 2-heteroaryl substituted indole derivatives, precursors thereof, and therapeutic uses of such compounds, having the structural formula (Ia) below: and to their pharmaceutically acceptable salt, compositions and methods of use. Furthermore, the invention relates to novel 2-heteroaryl substituted indole derivatives that are suitable for imaging amyloid deposits in living patients, their compositions, methods of use and processes to make such compounds. More specifically, the present invention relates to a method of imaging amyloid deposits in brain in vivo to allow antemortem diagnosis of Alzheimer's disease as well as measuring clinical efficacy of Alzheimer?s disease therapeutic agents.

Abstract: The present invention provides agents and methods for dual modality virtual colonoscopy that gives both anatomical and functional information using hybrid CT/PET scanning. In preferred embodiments, the present invention provides radiolabeled tumor-specific agents and methods for distinguishing benign polyps from malignant tumors. In further embodiments, the present invention provides compositions and methods useful for distinguishing morphological and functional subregions of a selected region of tissue based on relative levels of phospholipid metabolism. Preferred radiolabeled tumor-specific agents are phospholipid ether analogs labeled with a halogen radioisotope. In certain preferred embodiments, the compositions including radiolabeled phospholipid ether analogs have therapeutic actions in addition to functionally identifying malignant tissue.

Abstract: The present invention relates to novel heteroaryl substituted imidazopyridine derivatives, precursors thereof, and therapeutic uses of such compounds, having the structural formula (Ia) and to their pharmaceutically acceptable salt, compositions and methods of use. Furthermore, the invention relates to novel heteroaryl substituted imidazopyridine derivatives that are suitable for imaging amyloid deposits in living patients, their compositions, methods of use and processes to make such compounds. More specifically, the present invention relates to a method of imaging amyloid deposits in brain in vivo to allow antemortem diagnosis of Alzheimer's disease as well as measuring clinical efficacy of Alzheimer's disease therapeutic agents.

Abstract: The present invention relates to a method of suppressing bone marrow (BM) and treating conditions that arise in or near bone such as cancer, myeloproliferative diseases, autoimmune diseases, infectious diseases, metabolic diseases or genetic diseases, with compositions having as their active ingredient a radionuclide complexed with a chelating agent such as macrocyclic aminophosphonic acid.

Abstract: Methods for significantly lowering the carbon-14 content, particularly of DNA and histones in vertebrates, especially humans, to significantly below normal background levels and thereby reduce chromosomal damage using dietary supplements based on low radiocarbon DNA and histone precursors optionally including selected low radiocarbon amino acids, preferably including those which contribute the largest share of histone carbon atoms. Administration of the supplements during the earliest and/or most active growth stages of life is particularly beneficial. Components of the low radiocarbon supplements can be produced using a photobioreactor, an aqueous reaction medium and low radiocarbon carbon dioxide. The photobioreactor can be integrated into a body of water or can comprise a mobile, floating structure. Low radiocarbon by-products of photosynthesis can be recycled for use in non-photosynthetic fermentation processes to increase the yield of desirable supplement components.

Abstract: The present invention relates to a method of suppressing bone marrow (BM) and treating conditions that arise in or near bone such as cancer, myeloproliferative diseases, autoimmune diseases, infectious diseases, metabolic diseases or genetic diseases, with compositions having as their active ingredient a radionuclide complexed with a chelating agent such as macrocyclic aminophosphonic acid.

Abstract: Chelators of the formulae (I), (II) and (III) and tricarbonyl complexes of radioisotopes of Tc and Re bound to them, for use in myocardial imaging.

Abstract: The present invention relates to a chelating agent of the general formula: (I), wherein m is 0 or 1; X is NR4 or S; Y is SR5, NHR5 or P(R5)2; R1 and R3 are the same or different and are selected from H, alkyl or aryl; R2 is H, COOH, NHR6 or (CH2)nCOOR6; R4 is H, alkyl, aryl, (CH2)nCOOR6 or (CH2)nOR6; R5 is H, alkyl, aryl, (CH2)nCOOR6 or (CH2)nOR6, R6 is H, alkyl or aryl; n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and when R1?R3?CH3, R2, R4 and R5 are not all three H. The invention further relates to a method and kit for the preparation of radiolabeled biomolecules while using the chelating agent.

Abstract: A near-infrared fluorescing contrast medium which exhibits superior imaging capability and is also difficult to accumulate in a living body, is disclosed, comprising a cyanine compound containing water-solubilizing groups and represented by the following formula. The imaging method by use thereof is also disclosed.

Abstract: A family of structurally rigid dopamine D3 receptor selective ligands is described. The family of structurally rigid dopamine D3 receptor selective ligands has the formula wherein A is cis or trans —CH?CH—, —C?C—, or cyclohexyl. B is cis or trans —CH?CH— or absent. R1 represents an optionally substituted phenyl group, wherein said substituents are selected from the group consisting of: hydrogen, halogen, amino, nitro, hydroxyl, alkoxy, alkyl, acyl and pyridyl, and said substitution may occur at any of the ortho, meta, or para positions, or R1 represents a heteroaromatic ring. A preferred heteroaromatic ring is indole, quinoxoline, pyridyl, pyrimidyl, or imidazole. R2 and R3 may be independently hydrogen or a halogen, or R2 alone may be C1, C2, or C3 alkoxy, and m is 1 or 2, and n is 0, 1, or 2.

Abstract: The present invention relates to the use of a compound of formula (I): in which R1 represents a radionuclide, Ar represents an aromatic nucleus, m is an integer varying from 2 to 4, R2 and R3 represent, independently of one another, a hydrogen atom, a (C1-C6)alkyl group, a (C1-C6)alkenyl group or an aryl group chosen from a phenyl, benzyl, imidazolyl, pyridyl, pyrimidinyl, pyrazinyl, indolyl, indazolyl, furyl and thienyl group, and their addition salts with pharmaceutically acceptable acids, in the preparation of a radiopharmaceutical composition intended for the diagnosis and/or treatment of melanoma.

Abstract: The present invention provides for substituted metal chelating compounds in which at least two of the chelating atoms are nitrogen which are directly attached to aromatic rings and one or more of those nitrogen atoms has attached thereto a substituent other than hydrogen, and methods for making and using these compounds.

Abstract: The present invention relate to a method for monitoring a response to a therapy on a mammal having a neurodegenerative or neuroinflammatory disorder. According to a preferred embodiment, the method comprising the steps of: a) imaging the mammal using a radio-labeled peripheral benzodiazepine receptor ligand; b) administrating in the mammal at least one anti-amyloid or anti-neuroinflammatory agent; c) imaging the mammal of step b) using a radio-labeled peripheral benzodiazepine receptor ligand; and d) detecting the level of CNS neuroinflammation by the signals from the radio-labeled peripheral benzodiazepine receptor ligand.