Abstract: The invention provides a method of detecting blood flow abnormality or variation in a human or non-human body, said method comprising administering into the cardiovascular system of a said body a contrast enhancing amount of an intravascular paramagnetic metal containing magnetic resonance imaging contrast agent, subject said body to a magnetic resonance imaging procedure capable of generating from magnetic resonance signals from said body a series of temporally spaced images of at least a part of said body into which said agent passes, and detecting temporal variations in said signals or images whereby to identify regions of abnormal or modified blood flow in said body and to indicate the degree of blood flow abnormality or modification therein.

Abstract: The present invention relates to a method of using a polyazamacrocyclic compound or a salt thereof to measure intracellular metal ions formula ##STR1## where x is 2, 3 or a combination of p 2(s) and q 3(s) where p +q=y;y is 3 or 4;R is (CH.sub.2).sub.z P(=O)R.sup.1 R.sup.2;R.sup.1 is R.sup.3 or OR.sup.3 where R.sup.3 is alkyl, cycloalkyl or aryl;R.sup.2 is H, alkyl or ##STR2## where R.sup.4 is alkyl, cycloalkyl or aryl; and z is 1 to 3.

Abstract: The invention relates to compositions that comprise (1) lipophilic cationic organometallic complexes, particularly hexakis(2-methoxyisobutylisonitrile)technetium(I) complex, and (2) an agent that decreases the intramembrane potential of a living cell. Agents which decrease the intramembrane potential of a living cell include the lipophilic anions, especially tetraphenylborate anion. The invention also relates to methods in which the compositions are administered in vivo and in vitro when it is desirable to obtain enhanced cellular accumulation of lipophilic cationic organometallic complexes. The compositions and methods are useful for diagnosis and treatment, particularly in vivo tissue imaging.

Abstract: A process for reducing the non-target organ accumulation of immunoconjugates administered in vivo during therapeutic or diagnostic procedures involves the use of immunoconjugates comprising linkers that are cleavable at the non-target organs. The linkers are cleavable under conditions present, or induced, at one or more non-target organs, which include the kidneys or the liver.

Abstract: An improvement is provided to a method for obtaining an in vivo MR image of an organ or tissue of an animal or human subject, of the type including administering to the subject as a contrast agent to enhance such MR image an effective amount of a colloid including superparamagnetic metal oxide particles dispersed in a physiologically acceptable carrier. In accordance with the improvement, the method includes preparing the colloid in a manner that provides a reduction in toxicity in comparison with that associated with administration of the colloid after terminal sterilization. The improvement may include sterilizing the colloid by filtration. In an additional embodiment, the colloid may be sterilized by filtration and preserved by lyophilization. The colloid may be lyophilized in the presence of a compatible excipient. The excipient utilized may include a dextran or a citrate anion. Other embodiments include related compositions and methods.

Abstract: The present invention relates to contrast enhancing agents, conjugates thereof, pharmaceutical compositions thereof, and methods for diagnostic analysis, particularly NMR image analysis using these agents. The contrast enhancing agents are chelates of paramagnetic, ferromagnetic or diamagnetic metal ion(s) complexed with new lipophilic complexing acids related to polyaminopolycarboxylic acids.

Abstract: Methods of providing an image of the gastrointestional region of a patient and diagnosing the presence of any tumorous tissue in that region using contrast media comprising a combination of at least one polyphosphorylated aliphatic or polyphosphorylated alicyclic compound and at least one paramagnetic ion, wherein the aliphatic and alicyclic compounds comprise at least five carbon atoms, is described. Also described are diagnostic kits for gastrointestinal imaging which include the subject contrast media.

Abstract: Novel magnetic resonance imaging agents comprise complexes of paramagnetic ions with hydrazide derivatives of polyaminocarboxylic acid chelating agents. These novel imaging agents are characterized by excellent NMR image-contrasting properties and by high solubilities in physiological solutions. A novel method of performing an NMR diagnostic procedure involves administering to a warm-blooded animal an effective amount of a complex as described above and then exposing the warm-blooded animal to an NMR imaging procedure, thereby imaging at least a portion of the body of the warm-blooded animal.

Abstract: Novel magnetic resonance imaging agents methods utilize complexes of paramagnetic ions with alkoxyalkylamide deriviatives of diethylenetriaminepentaacetic acid ("DTPA") or ethylenediaminetetyraacetic acid ("EDTA"). These novel imaging agents are characterized by excellent NMR image-contrasting properties and by high solubilities in physiological solutions.The complexes are represented by the following formula: ##STR1## wherein A is --CH.sub.2 CH.sub.2 -- or ##STR2## and M.sup.+Z is a paramagnetic ion of an element with an atomic number of 21-29, 42-44 or 58-70, and a valence number, Z, of 2 or 3; R.sup.1 is --O.sup.- or R.sup.3 --N--R.sup.2, R.sup.2 is --(CH.sub.2 CH.sub.2 O).sub.n --R.sup.4, n is 1-10, R.sup.4 is alkyl or aryl, R.sup.3 is H, R.sup.2, alkyl, hydroxy, alkoxy, cycloalkyl or aryl, wherein Z of the R.sup.1 groups are --O.sup.- and the remainder of the R.sup.1 groups are R.sup.2 -N--R.sup.3 groups.

Abstract: Novel magnetic resonance imaging agents and methods which utilize complexes of paramagnetic ions with alkoxyalkylamide derivatives of diethylenetriaminepentaacetic acid ("DTPA") or ethylenediaminetetraacetic acid ("EDTA"). These novel imaging agents are characterized by excellent NMR image-contrasting properties and by high solubilities in physiological solutions. The complexes are represented by the following formula: ##STR1## wherein A is --CH.sub.2 CH.sub.2 -- or ##STR2## and M.sup.+z is a paramagnetic ion of an element with an atomic number of 21-29, 42-44 or 58-70, and a valence, Z, of 2 or 3; the R groups may be the same or different and are selected from the group consisting of -O.sup..crclbar. and lower alkoxyalkylamino groups having from 2 to about 6 carbon atoms, wherein the number of R groups -O.sup..crclbar. equals Z and the remaining R groups are lower alkoxyalkylamino, equal to 4-Z when A is --CH.sub.2 CH.sub.

Abstract: Methods for building bone in a human or other animal subject, comprising administering to said subject a safe and effective amount of calcium citrate malate. The calcium citrate malate is preferably administered for at least about three months. A preferred method of the invention is for the treatment of osteoporosis. The calcium citrate malate comprises a complex or a mixture of calcium salts having a ratio of moles citrate to moles malate of from about 1:0.16 to about 1:13.5. The calcium citrate malate is preferably administered in an oral dosage form, containing pharmaceutically-acceptable carriers and excipients.

Abstract: There is provided a method of generating enhanced images of the human or non-human animal body, for example for use in medical diagnosis, which involves administering to the body a positive MRI contrast agent which is body tissue- or body duct-specific following the particular mode of administration and a negative MRI contrast agent which preferably also is body tissue- or body duct-specific. Thereafter a magnetic resonance image is generated of a part of the body containing the negative and positive contrast agents or their paramagnetic, ferromagnetic or superparamagnetic biodegradation products. Contrast media suitable for use in this new image generating method are also provided.

Abstract: The invention relates to a method of using zeolite enclosed paramagnetic ions as image brightening or image contrast agents. In particular, zeolite enclosed trivalent gadolinium is useful in MRI studies of the entire gastrointestinal tract, providing excellent images. Zeolite-enclosed gadolinium complexes may be conveniently administered in oral preparations without side effects of diarrhea. Other transition metal ions, including divalent manganese may be enclosed in any suitable zeolite which has ion exchange properties sufficient to exchange the selected metal.

Abstract: A paramagnetic oil emulsion for magnetic resonance imaging composed of about 5 to about 30 volume percent oil and about 70 to about 95 volume percent aqueous-based paramagnetic agent carrier, at least one of the aqueous-based paramagnetic agent carrier and the oil having dissolved therein a magnetic resonance image contrast effective and less than a toxic amount of at least one soluble paramagnetic agent. The paramagnetic oil emulsion provides high intensity magnetic resonance signals in the gastrointestinal tract for MRI evaluation of the abdomen and pelvis, particularly in the distal bowel regions.

Abstract: A method for determining the diuretic potency of candidate drugs as inhibitors of ADH-elicited water channels is disclosed. In a preferred embodiment, such diuretic potency of candidate drugs is determined by suspending vesicles containing ADH water channels in an aqueous suspending medium, incorporating the candidate into the suspension, rapidly changing the pH of the suspending medium and thereafter detecting the proton permeability of the water channels. The proton permeability in the presence of the candidate drug can then be compared to the proton permeability of water channels under similar conditions without the presence of the candidate drug to determine the diuretic potency of the candidate drug to inhibit ADH-elicited water channels.

Abstract: A method of determining the glomerular filtration rate of a subject comprises (1) obtaining a serum sample S.sub.pre and a urine sample U.sub.pre from a subject; (2) administering to the subject an amount of a paramagnetic substance that is filtered by the kidneys and is readily detectable by NMR in serum and urine; (3) allowing for the concentration of the substance to equilibrate between the blood and the extravascular spaces; (4) separating an aliquot of the urine sample v.sub.A and obtaining a serum sample from the subject at the time t.sub.A ; (5) calculating a urine rate (v/a).sub.A from the formula (v/a).sub.A =V.sub.A /a.sub.

Abstract: Gadolinium and calcium chelates of DTPA (diethylenetriaminepentaacetic acid) bisamides, such as a composition comprising a gadolinium chelate of a 6-carboxymethyl-3,9-bis (hydroxyalkyl-carbamoylmethyl)-3,6,9-triazaundecanedioic acid and a calcium chelate of a 6-carboxymethyl-3,9-bis(hydroxyalkyl-carbamoylmethyl)-3,6,9- triazaundecanedioic acid, are disclosed for use as magnetic resonance imaging contrast media.

Abstract: Paramagnetic chelates, as for example, Gadolinium diethylenetriaminepentaacetic acid (DTPA), manganese, ethylenediaminetetraacetic acid (EDTA), and others used as magnetic resonance imaging contrast agents are more toxic acutely when injected in high concentration or at rapid rates. The use of effective amounts of calcium in the form of, calcium chloride, calcium gluconate, or balanced salt solutions substantially reduces this toxicity without the need to add additional ligand.

Abstract: This invention concerns a method for using an ion exchange resin as a pharmaceutical for treating circulatory disturbances especially to aid in combating circulatory vessel constrictions or occlusions. An example of the method uses Resonium A resin.

Abstract: Novel catecholamine solutions for physiological uses are provided at a pH in the range of 1.0-5.0, comprising catecholamine, acetylcysteine, chelating agent and buffering agents. The compositions are stabilized from oxidation without the use of sulfites and are preferably administered by inhalation.

Abstract: An agent for cleaning and dissolving tartar or removable oral prostheses comprises a solution of a phosphonic acid base chelating agent or agents as the active agents in water, the phosphonic acid base chelating agent or agents being selected from the group consisting of aminotrimethylphosphonic acid, hydroxyethylidenephosphonic acid and ehtylenediaminetetramethylphosphonic acid as well as their alkali metal salts, and being contained in water in an amount of 15 to 90 weight %, the solution being of a pH of 7 or lower.

Abstract: An improved composition for dissolution of renal calculi is disclosed. The composition includes citric acid, preferably at about 10 to about 15% by weight, and an effective amount of a pharmacologically acceptable chelating agent such as EDTA in a sterile aqueous solution having a pH between about 3 and about 4.5. In vivo irrigation with the improved formulation, optionally in combination with incident ultrasound therapy promotes rapid stone dissolution with minimal complications for the patient.

Abstract: Ethylene Diamine Hydroxy Phenylacetic Acid (EDHPA) type chelators strongly bind paramagnetic metal ions to provide excellent contrast agents for magnetic resonance (MR) imaging. The magnetic dipole generated by unpaired electrons within the paramagnetic (PM) atom, causes a local reduction in the bulk magnetic field of the MR system. The resulting shortening of the T1 (spin lattice) relaxation time in the hydrogen protons within the area of interest, causes an intense "free induction signal" and a corresponding modulation in the collected scanning data. The tissue of organ of interest appears on the MR display as a high intensity of white area. Background tissue is displayed as darker or lower intensity greys. Each member chelator EDHPA' of the EDHPA family of chelators, is a phenolic analog of EDTA, with variations in the para position radical (PR) of the phenol ring.

Abstract: Method of controlling the rate of tryptophan metabolism in the liver of humans by parenteral administration of tin or chromium protoporphyrin to increase the rate, and the administration of cobalt protoporphyrin to decrease the rate.

Abstract: The present invention relates to polymeric iron chelators based upon hydroxamic acids having the general formula: ##STR1## wherein R is hydrogen or lower alkyl. The present compound is useful for the treatment of iron overload disorders particularly arising from iron poisoning and the disease .beta.-thalassemia otherwise known as Cooley's Anemia. The polymeric hydroxamic acids of the present invention exhibit high selectivity for iron, good water solubility for both the chelator and its iron complex, low toxicity and, most significantly, increased bioactivity, i.e., the ability to remove iron in vivo.

Abstract: A protein-polysuccinimide complex wherein a biologically active protein is combined with a polysuccinimide having a mean molecular weight of 2,000 to 1,000,000 and consisting of constitutive units represented by the following formulae: ##STR1## Said complex can be labelled with a radio-metal and can be used as a radioactive diagnostic in the field of nuclear medicine.