Abstract: Tridentate mono-anionic ligands have the structureX-A-Y-Q-Zwhere each of X and Y is independently P, As or N,Z is phenol, thiophenol or thiol, andA and Q are hydrocarbon linking groups.The ligands from cationic complexes with Technetium-99m, e.g. [Tc.sup.III K.sub.2 ].sup.+ where K is the ligand, having useful imaging properties.

Abstract: Amide-thiolate ligands having improved metal chelate formation kinetics are disclosed. The ligands include a tertiary amine strategically located to facilitate rapid formation of an amine-amide-thiolate intermediate complex, followed by transfer of the metal to a thermodynamically stable amide-thiolate complex. The amide-thiolate ligands of the present invention may be used for post formed labeling of biological substances for use in the fields of diagnosis and therapy.

Abstract: The invention relates to compounds having the general formula I ##STR1## where A if required can contain a functional and/or activated group C for coupling to selectively concentrating compounds or can contain a selectively concentrating compound coupled via the group C. B and B' are functional groups for coordinate bonding of groups carrying metal ions. The novel compounds are for forming complexes with radioactive metal ions, more particularly rhenium and technetium isotopes, and are used in medical diagnosis and therapy.

Abstract: The invention relates to the preparation of complexes of 99m-technetium, 186-rhenium or 188-rhenium usable as radiopharmaceutical products.For this preparation, an oxidized compound of .sup.99m Tc, .sup.186 Re or .sup.188 Re, e.g. an alkali metal or ammonium perrhenate or pertechnetate, is reacted with a first ligand chosen from the group of substituted or unsubstituted, aliphatic and aromatic phosphenes and polyphosphenes and a second nitrogenous ligand constituted by an ammonium nitride or a pharmaceutically acceptable metal or by a nitrogenous compound having a >N--N< unit, such as hydrazine, a hydrazine derivative, dithiocarbazic acid and dithiocarbazic acid derivatives.The product obtained can be used as it is as a radiopharmaceutical product or can serve as an intermediate for the preparation of other radiopharmaceutical products by exchange reaction with a third ligand, a monoclonal antibody or an antibody fragment.

Abstract: Technetium-99m complexes of crown thioethers having 3 to 6 donor sulphur atoms joined into a macrocyclic ring by C2 or C3 groups, for example 1,4,7-trithiacyclononane (9S3); and of tripodal ligands having more than 3 donor sulphur atoms joined by C2 or C3 groups, for example, 1,1,1-tris(((2-methylthio)ethylthio)-methyl)ethane.

Abstract: The invention relates to a radiopharmaceutical product more particularly having a cardiac tropism, incorporating a nitride complex of a transition metal and the process for the preparation thereof.This complex complies with the formula:(M.ident.N)L.sup.1 L.sup.2 (I)in which M is a transition metal, e.g. Tc99m, Re 186 or Re 188 and L1 and L2, which can be the same or different, comply with the formula: ##STR1## in which R.sup.1 and R.sup.2 can be alkyl radicals, V and W can be O, S or Se, n=0 or 1, m=0 or 1, and Y represents N, P or As.

Abstract: Porphyrin complex compounds, consisting of a mesotetraphenylporphyrin ligand, optionally at least one ion of an element with atomic numbers 13, 21, 32, 37-39, 42-44, 49, 50 or 57-83 as well as optionally cations of inorganic and/or organic bases, amino acids or amino acid amides, are valuable diagnostic and therapeutic agents.

Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described.

Abstract: Radiopharmaceuticals consisting essentially of a lipophilic, charge neutral radionuclide complex of a diaminedithiol ligand having 1-4 ester groups of the formula --A--COOR where A is a straight or branched chain alkylene of 0-10 carbon atoms and R is an alkyl group of 1-10 carbon atoms are useful in radioimaging brain perfusion in primates. Ester-substituted diaminedithiols in sterile, pharmaceutically acceptable form, and kits of the diaminedithiols and sterile, non-pyrogenic reducing agents for reducing preselected radionuclides are also provided. Technetium-99m is a preferred radionuclide.

Abstract: Proteins containing one or more disulfide bonds are radiolabeled with radionuclides of technetium or rhenium for use in diagnosis and treatment of a variety of pathologic conditions. Radiolabeling is accomplished by partial reduction of the disulfide bonds of the protein using Sn (II), or using other reducing agents followed by the addition of Sn (II), removal of excess reducing agent and reduction by-products, and addition of a specified amount of pertechnetate or perrhenate reducing agent, such as stannous tartrate, with the addition accomplished in such a manner that further reduction of the protein is limited. The resulting product may be stored frozen or lyophilized, with radiolabeling accomplished by the addition of pertechnetate or perrhenate solution.

Abstract: The subject of the present invention is compounds which correspond to the following general formula: ##STR1## in which R.sub.1 and R.sub.3 independently of one another represent H, an alkyl, alkenyl, cycloalkyl, aryl, arylalkyl or an alkylaryl group, a heterocycle, or groups which are unsubstituted or substituted, in particular by one or more hydroxyl or alkoxy groups or halogen;n represents an integer from 1 to 5;i in each case takes values from 1 to n for the n successive ##STR2## links; R.sub.2, R.sub.4.sup.i and R.sub.5.sup.i independently of one another represent H, an alkyl, alkenyl, aryl, alkoxy, hydroxyalkyl, alkoxyalkyl, amido, acyl or carboxyalkyl group, or a salt, or an alkyl ester of the latter; or R.sub.4.sup.i and R.sub.5.sup.i together form an oxo group ##STR3## R.sub.6 and R.sub.7 represent H, or R.sub.6 and R.sub.7 together form an oxo group ##STR4## x represents a 5- or 6-membered heterocycle which contains at least one nitrogen atom, or, in the event that ##STR5## where R.sub.8 and R.sub.

Abstract: The invention relates to a method of preparing a radiolabelled technetium complex by bringing Tc-99m in the form of a pertechnetate solution in a complex-forming reaction with a compound of the general formula ##STR1## wherein R.sub.1 -R.sub.12 each independently represents a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group, a carboxy group, or a carboxy(C.sub.1 -C.sub.4)alkyl group;or whereinR.sub.1 +R.sub.2, R.sub.3 +R.sub.4, R.sub.5 +R.sub.6, R.sub.7 +R.sub.8, R.sub.9 +R.sub.10 and R.sub.11 +R.sub.12 each independently represent an oxo or imino function;and wherein furthermore:R.sub.13 is a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group or a carboxy(C.sub.1 -C.sub.4)alkyl group;R.sub.14 is a hydrogen atom or an amino group; n is 0, 1 or 2;A represents an amino group or a mercapto group; andB represents a mercapto group, or a group of the general formula NH--Z--CO--NH--.sub.m Z--COOH, wherein:Z is an optionally substituted C.sub.1 -C.sub.

Abstract: Novel chelating compounds and the corresponding radionuclide metal chelates are useful for radiolabeling proteins such as antibodies with radionuclide metals such as .sup.99m Tc, .sup.186 Re, and .sup.188 Re. The chelating compounds are of the following formulas: ##STR1## wherein each R is a protecting group;Q is hydrogen or a protecting group;each T is independently chosen from hydrogen, lower alkyl groups of from 1 to about 6 carbon atoms, electron withdrawing groups, and lower alkyl groups of from 1 to about 6 carbon atoms substituted with electron withdrawing group(s);X represents O, S, or NH;each R' is independently selected from:--(CH.sub.2).sub.n --COOH with n=0 to about 4,--(CH.sub.2).sub.n --Z, wherein Z represents a conjugation group and n is 0 to about 4,hydrogen, anda lower alkyl group of from 1 to about 6 carbon atoms;each R" is independently selected from:--(CH.sub.2).sub.

Abstract: Chelating compounds of specified structure are useful for radiolabeling targeting proteins such as antibodies. The radiolabeled antibodies, or catabolites thereof, demonstrate improved biodistribution properties, including reduced localization within the intestines.

Abstract: A process for preparing a radiopharmaceutical composition comprising a technetium 99m chelate complex, comprises the steps of:(1) mixing (a) HSCH.sub.2 CO--NHCH.sub.2 CO--NHCH.sub.2 CO--NHCH.sub.2 COOH (mercaptoacetylglycylglycylglycine, MAG3), (b) a watersoluble reducing agent, (c) a water-soluble stabilizing agent in an amount of not less than 70 mol per 1 mol of the water-soluble reducing agent and (d) a pertechnetate at a pH of about 8 to 11; and(2) heating the resultant mixture at a temperature of about 90 to 140.degree. C.Said process removes any troublesome labeling operation at the diagnostic site and relieve the practitioners from the exposure to radiation during the labeling operation.

Abstract: The present invention relates to novel preorganized hexadentate ligands suitable for complexing with a radionuclide to form imaging agents for diagnostic purposes. The ligands have the formula: ##STR1## wherein a) R.sub.2 is hydrogen and R.sub.3 is methyl; or R.sub.2 and R.sub.3 together form a methoxy benzene ring.

Abstract: Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.

Abstract: The invention relates to a method for labeling substances with--in particular radioactive--technetium or rhenium isotopes with the aid of N-substituted or C-substituted macrocyclic amine derivatives of the formula I and/or II ##STR1## in which R.sup.1 -R.sup.7, Y, m, n, o, p, f, g, h, i and j have the stated meanings, and to the use of these labeled substances, especially in medical diagnosis.

Abstract: Novel bifunctional bis-quinolinols are provided as well as their chelates and processes for their production. The quinolinols can be attached to organic substrates before or after chelation and are useful for diagnostic and therapeutic purposes.

Abstract: A new method for synthesizing 2-alkoxyisobutylisonitrile is provided in which isobutylene is used as the starting material. The haloalkoxylation of isobutylene in alcohol medium gives 2-alkoxyisobutylhalide which is then converted to 2-alkoxyisobutylamine. In the basic condition, the reaction of 2-alkoxyisobutylamine with chloroform produces 2-alkoxyisobutylisonitrile. The synthesis process contains three steps by which a higher yield is achieved. 2-Alkoxyisobutylisonitrile is labelled with technetium-99m by exchange labelling of stable tetrakis(2-alkoxyisobutylisonitrile)copper(I) complex. Tetrakis(2-alkoxyisobutylisonitrile)copper(I) complex can be prepared by the exchange of acetonitrile molecules in tetrakis(acetonitrile)copper(I) complex with isonitrile ligands.

Abstract: There are provided chelating agents particularly useful for the preparations of diagnostic and therapeutic agents for magnetic resonance imaging, scintigraphy, ultrasound imaging, radiotherapy and heavy metal detoxification, said agents being compounds of formula X--CHR.sub.1 --NZ--(CHR.sub.1).sub.n --A--(CHR.sub.1).sub.m --NZ--CHR.sub.1 --X wherein (each of the groups Z is a group --CHR.sub.1 X or the groups Z together are a group --(CHR.sub.1).sub.q --A'--(CHR.sub.1).sub.r --, where A' is an oxygen or sulphur atom or a group --N--Y; A is a group --N--Y or A--(CHR.sub.1).sub.m -- represents a carbon-nitrogen bond or, when the groups Z together are a group --(CHR.sub.1).sub.q --A'--(CHR.sub.1).sub.r --, A may also represent an oxygen or sulphur atom; each Y, which may be the same or different, is a group --(CHR.sub.1).sub.p --N(CHR.sub.1 X).sub.2 or a group --CHR.sub.1 X; each X, which may be the same or different, is a carboxyl group or a derivative thereof or a group R.sub.1 ; each R.sub.

Abstract: The invention relates to a method of preparing technetium chelate of the general formula ##STR1## wherein x is a sulphur atom or an imino group,Z is a hydrogen atom, a carboxy group, an alkoxycarbonyl group having 1-4 carbon atoms, an aminocarbonyl group, a sulpho group, an aminosulphonyl group or a carboxymethylaminocarbonyl group,Tc represents technetium-99m,R.sub.1 is a hydrogen atom or an alkyl group having 1 or 2 carbon atoms, andR.sub.2, R.sub.4 and R.sub.5 are equal or different and represent hydrogen atoms or branched or non-branched alkyl groups having 1-4 carbon atoms, which alkyl groups are optionally substituted with an amino group, a hydroxy group, a mercapto group, a halogen atom, a carboxy group or an aminocarbonyl group,with the proviso that R.sub.3, R.sub.4 and R.sub.5 do not all three of them represent hydrogen atoms;as well as water-soluble salts of these compounds.

Abstract: Boronic acid adducts of metal dioxime complexes are useful as reagents for labeling proteins and other amine-containing compounds.

Abstract: Methods for rapidly labeling sulfhydryl-containing antibodies or fragments with technetium or rhenium radioisotopes are disclosed. The method generally involves combining an aqueous mixture of the radiometal in an oxidized form, a reducing agent and a water-soluble polyhydroxycarbonylic acid ligand to form a stable complex of the radiometal in its reduced state and contacting the mixture with the sulfhydryl-containing antibody or fragment to produce a radiometal-labeled antibody or fragment.

Abstract: Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.

Abstract: The invention relates to a diagnostic or radiotherapeutic composition, comprising a hydrogen containing compound in addition to a pharmaceutically acceptable formulation means and optionally an inactive carrier and/or one or more auxiliary substances, wherein the hydrogen containing compound comprises at least one deuterium atom. The invention further relates to a compound to be used for said composition and to a kit for preparing a radio-diagnostic composition.

Abstract: Chelating compounds of specific structure are useful for radiolabeling targeting proteins such as antibodies. The radiolabeled antibodies, or catabolites thereof, demonstrate improved biodistribution properties, including reduced localization within the intestines.

Abstract: The invention relates to a .sup.99m Tc-labeled liposome encapsulated protein and to a highly efficient method of radiolabeling liposome encapsulated protein. In particular, a .sup.99m Tc carrier is used to label preformed liposome-encapsulated hemoglobin. The liposome-encapsulated .sup.99m Tc labeled hemoglobin is highly stable in vitro and in vivo and is suitable for a variety of clinical uses, including biodistribution imaging studies. The invention also relates to a method of using technetium-.sup.99m labeled liposome encapsulated hemoglobin to label neutrophils. A kit method which could be used for the convenient preparation of .sup.99m Tc-labeled liposome encapsulated hemoglobin for clinical use is also disclosed.

Abstract: The invention relates to the efficient preparation of radionuclide labeled liposomes and radionuclide-labeled liposome-encapsulated protein. In particular, a .sup.99m Tc carrier is used to label preformed liposomes or liposome-encapsulated hemoglobin. .sup.99m Tc-labeled liposomes and liposome-encapsulated .sup.99m Tc labeled hemoglobin are highly stable in vitro and in vivo and are suitable for a variety of clinical uses, including biodistribution imaging studies. The invention also relates to a method of labeling neutrophils using .sup.99m technetium-labeled liposomes or liposome-encapsulated hemoglobin. A kit method useful for the convenient preparation of .sup.99m Tc-labeled liposomes or liposome-encapsulated hemoglobin for clinical use is also disclosed.

Abstract: A chelating compound of the formula:(R--NHOC--CH.sub.2).sub.n --A--(CH.sub.2 COOH).sub.m (I)wherein R is an aromatic ring-containing organic group, A is a residue of an aminopolyacetic acid excluding acetic acid groups (--CH.sub.2 COOH) therefrom, m is an integer of at least two and n is an integer of 1 or 2, or its salt, which has a specificity to a hepatobiliary system so that a complex formed between said chelating compound and a metallic element through a coordinate bond is useful and a diagnostic or therapeutic agent for hepatobiliary organs and tissues.

Abstract: Methods and compositions for enhancing magnetic resonance imaging in at least a portion of a warm-blooded animal.

Abstract: Macrocyclic derivatives of 1,4,7,10-tetraazacyclododecane of general formula (I) hereinbelow, wherein A is a group of formula (II) hereinbelow, in which R is H or alkyl or optionally substituted benzyl or a H(OCH.sub.2 CH.sub.2).sub.1-4-, Me(OCH.sub.2 CH.sub.2).sub.1-4-, or Et(OCH.sub.2 CH.sub.2).sub.1-4- group, X or O--R.sub.1, in which R.sub.1 is H or alkyl, hydroxyalkyl, alkoxyalkyl, alkoxyhydroxyalkyl or a polyoxaalkyl group or X is --NR.sub.2 R.sub.3, in which R.sub.2 and R.sub.3 are H or alkyl, hydroxyalkyl, alkoxyalkyl or alkoxyhydroxyalkyl, and B.sub.1, B.sub.2 and B.sub.3 have the same meanings as A or are H or a group of formula (III) hereinbelow, in which R.sub.4 is H or alkyl, Y is a O--R.sub.5 group, wherein R.sub.5 is H or alkyl, hydroxyalkyl, alkoxyalkyl, alkoxyhydroxyalkyl or a polyoxaalkyl group, or Y is a --NR.sub.6 R.sub.7 group, wherein R.sub.6 and R.sub.

Abstract: A method for radiolabeling a protein with a radioisotope of technetium of rhenium comprises the steps of contacting a solution of a protein containing a plurality of adjacent free sulfhydryl groups, or in particular cases, intact protein containing at least one disulfide group, with stannous ions, and then with radiopertechnetate or radioperrhenate, the amount of stannous ion being sufficient to substantially completely reduce the radiopertechnetate or radioperrhenate, and recovering radiolabeled protein.

Abstract: A high molecular compound useful as a non-radioactive carrier, which comprises at least one unit of (1) an asialoglycoprotein acceptor-directing compound and at least one unit of (2) a chelate-forming compound chemically bonded thereto, and which may be labeled with a radioactive metallic element to give a radioactive metallic element-labeled product useful as a radioactive diagnostic or therapeutic agent for liver.

Abstract: The present invention relates to novel technetium-99 m complexes and to methods of preparing the complexes. The present invention further relates to a radiopharmaceutical compositions comprising the complexes, to the use of the compositions for examining the renal function, and to a kit for preparing such compositions.

Abstract: A myocardial imaging agent for use in humans comprising a Tc(III) complex ligated in a planar position by a tetradentate ligand having incorporated therein four hard atoms and two furanone rings and in the axial positions by phosphines containing dioxanyl or ether moieties. The agent exhibits improved biodistribution, improved labeling and extremely rapid blood clearance following administration to a human. The agent has high myocardial uptake accompanied with exceptionally rapid hepatobilary clearance and extensive renal clearance to give sufficiently high heart/liver and heart/lung ratio that provide nearly ideal myocardial images in humans.

Abstract: Chelating compounds of specified structure are useful for radiolabeling targeting molecules such as antibodies. Cleavable linkers connect the radionuclide metal chelates to the antibodies. The radiolabeled antibodies have improved biodistribution properties, including reduced localization within the intestines and kidneys.

Abstract: The present invention relates to novel technetium-99m complexes and to methods of preparing the complexes. The present invention further relates to radiopharmaceutical compositions comprising the complexes, to the use of the compositions for examining the renal function, and to a kit for preparing such compositions.

Abstract: A non-radioactive labeling composition for preparation of a technetium 99m-labeled radioactive diagnostic agent, which comprises a small amount of a lyophilized product obtained from a stannous chloride solution having a high concentration of stannous chloride charged in a container.

Abstract: Chelated radionuclide compositions are provided for conjugation to polypeptides and carbohydrates. The resulting conjugates may be used in diagnosis and therapy.

Abstract: The present invention provides conjugates formed from calcified tissues targeting agents and radiolabeled compounds. One such conjugate comprises a chelate and a targeting agent that is capable of associating with calcified tissue, wherein the chelate contains at least one nitrogen atom or at least one sulfur atom or combinations thereof as the donor atoms.Another aspect of the invention provides methods for using the conjugates for diagnostic and therapeutic purposes, including those related to bone cancer.

Abstract: A high molecular compound useful as a non-radioactive carrier, which comprises at least one unit of (1) an asialoglycoprotein acceptor-directing compound and at least one unit of (2) a chelate-forming compound chemically bonded thereto, and which may be labeled with a radioactive metallic element to give a radioactive metallic element-labeled product useful as a radioactive diagnostic or therapeutic agent for liver.

Abstract: Complexes useful as radiopharmaceuticals contain the .sup.99m Tc-NO moiety and up to four organic ligands which confer biological target-seeking properties on the complex. Preferred are mono-cationic complexes, particularly having the formula[.sup.99m Tc(NO)L.sub.2 X].sup.+where X is halide or pseudohalide and L is a bidentate ligand for Technetium, which have interesting properties for use as heart visualizing agents. Examples of ligands include di-(dialkyl and diphenyl)phosphinoethanes and o-phenylenebisdimethylarsine. The complexes may be made by reacting generator eluate pertechnetate with a hydroxylamine salt and with the ligands, preferably in a single step by providing a reaction mixture containing the three reagents optionally in the presence of a reducing agent.

Abstract: An agent for imaging organs using a radioactive complex of a radioactive metal with a benzene ring having two 2-mercapto-2-methylpropylamino substituents where one of these mercapto substituents is substituted with a hydrocarbyl group.

Abstract: Methods and compositions for enhancing magnetic resonance imaging in at least a portion of a warm-blooded animal.

Abstract: The present invention provides metal chelating compounds, to chelates and chelate-targeting agent conjugates formed from the chelating compounds, and to methods for making and using these compositions. The chelating compounds incorporate two nitrogen atoms and three sulfur atoms ("N.sub.2 S.sub.3 "), two nitrogen atoms and four sulfur atoms ("N.sub.2 S.sub.4 "), or three nitrogen atoms and three sulfur atoms ("N.sub.3 S.sub.3 "). Metals, and metal oxides, capable of being chelated by the compounds include those that are radionuclides, such as .sup.99m Tc and .sup.186/188 Re.The targeting agent portion of the chelate-targeting agent conjugates provided includes antibodies, peptides, hormones, enzymes and biological response modifiers. Methods for making the conjugates are provided and encompass the addition of a metal, or metal oxide, to a chelating compound prior to attachment to a targeting agent as well as subsequent to the attachment.

Abstract: A polyaminedithiol compound of the formula: ##STR1## wherein R.sub.1, R.sub.2, R.sub.11 and R.sub.12 are each a lower alkyl group, R.sub.21 is a hydrogen atom or a lower alkyl group, and R.sub.3 and R.sub.13 are each a hydrogen atom or a nitrogen-containing organic group, provided that at least one of R.sub.3 and R.sub.13 is a nitrogen-containing organic group, which is used for imaging of the regional cerebral blood flow.

Abstract: Complexes useful as radiopharmaceutical imaging agents comprise technetium bonded to a ligand which generally can be described by the formula: ##STR1## wherein Z is N, C, B or P;the three Y groups can be the same or different, each characterized by the general formula ##STR2## and R.sup.1, R.sup.2, R.sup.3, R.sup.4, W, and X are further defined herein.

Abstract: Boronic acid adducts of technetium-.sup.99m imine-dioxime complexes are useful for imaging the myocardium, hepatobiliary system, brain and blood pool in humans and other mammalian species.

Abstract: This invention relates to an improved method for conducting scintigraphy to monitor of immunotoxins under clinical conditions. The improvement relates to the use of heterobifunctional chelators to bind radionuclides exclusively to the cytotoxic moiety of an immunotoxin.