Abstract: Macrocyclic chelating agents, optionally possessing more than one macrocyclic ring having at least two peptide linkages within the macrocyclic skeleton. The chelating agents are used for the preparation of paramagnetic metal chelates for use as MRI contrast agents.

Abstract: There are provided polychelants and their metal chelates which are useful in diagnostic imaging and in radiotherapy and which comprise a plurality of macrocyclic chelant moieties, e.g. DOTA residues, conjugated to a polyamine backbone molecule, e.g. polylysine. To produce a site-specific polychelate, one or more of the macrocyclic chelant carrying backbone molecules may be conjugated to a site-directed macromolecule, e.g. a protein. For example, adducts of a macrocyclic chelant can be formed by the process of (a) dispersing a carboxylic macrocyclic chelant in a polar, anhydrous solvent, (b) adding a base with a pKa sufficient to remove all carboxyl protons to create an amine salt of the chelant soluble in the solvent, (c) chilling the reaction mixture to between about 5.degree. C. and 55.degree. C.

Abstract: An imaging contrast medium comprising a physiologically tolerable multinuclear complex (as defined in claim 1) is disclosed. The multinuclear complex contains at least two, but preferably three or more contrast enhancing atoms. For X-ray or ultrasound imaging techniques heavy metal atoms are used to enhance contrast, whereas in Magnetic Resonance Imaging paramagnetic metal atoms are contrast enhancing. Molybdenum and tungsten are preferred contrast enhancing atoms. The medium may also be used therapeutically.

Abstract: The invention relates to the use as contrast enhancing agents in medical imaging, especially X-ray imaging, of multinuclear complexes, i.e. complexes, such as those of W2O2 (u2O)2, in which the complexed entity comprises at least two contrast enhancing atoms.

Abstract: There are disclosed polychelant compounds, that is multi-site metal chelating agents, and chelates formed therewith. The polychelants and especially their paramagnetic metal, heavy metal or radioactive metal polychelates are particularly suitable for use in diagnostic imaging, heavy metal detoxification or radiotherapy. The polychelants have a linear or branched oligomeric structure comprising alternating chelant and linker moieties bound together by amide or ester moieties the carbonyl groups whereof being adjacent the chelant moieties, each polychelant comprising at least two said chelant moieties capable of complexing a metal ion.

Abstract: There are disclosed polychelant compounds, that is multi-site metal chelating agents, and chelates formed therewith. The polychelants and especially their paramagnetic metal, heavy metal or radioactive metal polychelates are particularly suitable for use in diagnostic imaging, heavy metal detoxification or radiotherapy. The polychelants have a linear or branched oligomeric structure comprising alternating chelant and linker moieties bound together by amide or ester moieties the carbonyl groups whereof being adjacent the chelant moieties, each polychelant comprising at least two said chelant moieties capable of complexing a metal ion.

Abstract: N,N'-bis-(pyridoxal-5-phosphate)-alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal-5-phosphate)-1,2-cycloalkylenediamine-N,N'diacetic acids, and N,N'-bis-(pyridoxal-5-phosphate)-1,2-arylenediamine-N,N'diacetic acids, the corresponding monophosphate compounds and monoacetic acid compounds, and their salts and esters form stable, highly soluble chelates with paramagnetic metal ions, and are highly effective NMRI contrast agents. Preferred contrast agents are paramagnetic ion chelates of N,N'-bis-(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-cyclohexylenediamine-N,N'-diacet ic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-arylenediamine-N,N'-diacetic acid, and the soluble calcium salts thereof.

Abstract: Magnetic resonance imaging contrast media used to affect the relaxation times of atoms in body tissues undergoing NMR diagnosis are disclosed. Such media comprise (1) a paramagnetic, physiologically compatible complex of (a) a chelant consisting of a N-carboxy methylated tetraazacyclododecane, and (b) a paramagnetic ion of a lanthanide element of atomic numbers 59-70, or of a transition metal of atomic numbers 21-29, 42 or 44, or a physiologically compatible salt of such a complex, and (2) a toxicity-reducing amount of labile calcium ions. The labile calcium ions can be derived from a source other than a salt of said chelant, e.g. an inorganic or organic calcium salt. NMR image-enhancing compositions comprising NMR image-enhancing effective amounts of said contrast media and pharmaceutically acceptable diluents are also disclosed.

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 process of this invention for preparing Mn(II) chelate comprises forming the Mn(II) chelate by mixing manganese (II) oxide (insoluble) with an aqueous suspension comprising a molar equivalent or molar excess of the insoluble protonated chelating compound at a temperature of from 20.degree.to 50.degree. C. When the reaction is carried out with a protonated chelating agent in the absence of base, a precipitate of the protonated Mn(II) chelate is formed. A low osmolarity MN(II) chelate solution can be formed from the precipitates by dissolving them in an aqueous solution of base. When the initial chelate forming reaction is carried out in a solution containing a molar equivalent or excess of sodium hydroxide, a low osmolarity solution of the Mn(II) chelate is directly formed with most chelating agents. Preferred chelating compounds for this process include DPDP, DTPA, DCTA, EDTP, DOTA, DOXA, DO3A and EDTA.

Abstract: N,N'-bis-(pyridoxal-5-phosphate)-alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal-5-phosphate)-1,2-cycloalkylenediamine-N,N'-diacetic acids, and N,N'-bis-(pyridoxal-5-phosphate)-1,2-arylenediamine-N,N'-diacetic acids, the corresponding monophosphate compounds and monoacetic acid compounds, and their salts and esters form stable, highly soluble chelates with paramagnetic metal ions, and are highly effective NMRI contrast agents. Preferred contrast agents are paramagnetic ion chelates of N,N'-bis-(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-cyclohexylenediamine-N,N'-diacet ic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-arylenediamine-N,N'-diacetic acid, and the soluble calcium salts thereof.

Abstract: Manganese(II) chelates of N,N'-bis-(pyridoxal)alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal)-1,2-cycloalkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal)-1,2-arylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal)alkylenediamine-N-acetic acids, N,N'-bis-(pyridoxal)-1,2-cycloalkylenediamine-N-acetic acids, N,N'-(pyridoxal)-1,2-arylenediamine-N-acetic acids, and their salts are highly stable, superior NMRI contrast agents. They maintain the manganese(II) ion in the +2 valence state. Preferred contrast agents are manganese(II) ion chelates of N,N'-bis-(pyridoxal)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal)trans-1,2-cyclohexylenediamine-N,N'-diacetic acid, and the salts and esters thereof.

Abstract: N,N'-bis-(pyridoxal-5-phosphate)-alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal-5-phosphate)-1,2-cycloalkylenediamine-N,N'-diacetic acids, and N,N'-bis-(pyridoxal-5-phosphate)-1,2-arylenediamine-N,N'-diacetic acids, the corresponding monophosphate compounds and monoacetic acid compounds, and their salts and esters form stable, highly soluble chelates with paramagnetic metal ions, and are highly effective NMRI contrast agents. Preferred contrast agents are paramagnetic ion chelates of N,N'-bis-(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-cyclohexylenediamine-N,N'diaceti c acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-arylenediamine-N,N'-diacetic acid, and the soluble calcium salts thereof.

Abstract: A process for making a solution of a complex of an oxamine and a polyvalent paramagnetic metal comprising contacting a solution of the oxamine with (a) the insoluble hydroxide of the polyvalent paramagnetic metal in water, or (b) an alkoxide of the metal is a non-aqueous solvent, thereby to form a solution of a complex of the oxamine and the metal. The complex, preferably ferrioxamine, is an improved NMR image enhancer compared even with ferrioxamine made conventionally, characterized by a high LD.sub.50.

Abstract: Complexes of a highly paramagnetic polyvalent metal, e.g., a lanthanide such as gadolinium, or of a less paramagnetic metal, e.g., iron, manganese, copper, cobalt, chromium or nickel, with a bisalkylamide of diethylenetriaminepentaacetic acid of the formula: ##STR1## wherein three groups M are hydroxyl groups and the remaining two groups M are NHR groups in which each group R is an alkyl group of the formula --(CH.sub.2).sub.n CH.sub.3 where n is zero or an integer of from 1 to 17, are disclosed. These complexes are useful as magnetic resonance imaging contrast enhancers.

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: The presence and location of amyloid deposits in an organ or body area of a patient is effected by intravenous administration of novel radioactive iodine-labeled amyloid binding compounds and preferably .sup.123 I-labeled compounds to the patient and sensing radiation emitted from the organ or body area.

Abstract: In a method of imaging body tissue in a patient, comprising administering to the patient an effective amount of a pharmaceutical agent for effecting the relaxation times of atoms in body tissues undergoing NMR diagnosis, whereby image contrast is enhanced, said agent comprising an amount, effective to effect such relaxation times, of a paramagnetic, physiologically compatible salt of a physiologically compatible chelate complex of an ion of a lanthanide element of atomic numbers 57-70, or of a transition metal of atomic numbers 21-29, 42, or 44; and a pharmaceutically acceptable carrier, and subjecting the patient to NMR tomography, the improvement wherein said salt of said chelate complex is the calcium or magnesium salt. Such salts are new as are some of the complexing chelates.

Abstract: The presence and location of amyloid deposits in an organ or body area of a patient is effected by intravenous administration of novel radioactive iodine-labeled amyloid binding compounds and preferably .sup.123 I-labeled compounds to the patient and sensing radiation emitted from the organ or body area. Novel non-radioactive iodine substituted amyloid binding compounds and amyloid binding compounds which are readily iodinated are further aspects or the invention.

Abstract: Manganese(II) chelates of N,N'-bis-(pyridoxal)-alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal)-1,2-cycloalkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal)-1,2-arylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal)-alkylenediamine-N-acetic acids, N,N'-bis-(pyridoxal)-1,2-cycloalkylenediamine-N-acetic acids, N,N'-bis-(pyridoxal)-1,2-arylenediamine-N-acetic acids, and their salts are highly stable, superior NMRI contrast agents. They maintain the manganese(II) ion in the +2 valence state. Preferred contrast agents are manganese(II) ion chelates of N,N'-bis-(pyridoxal)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal)trans-1,2-cyclohexylenediamine-N,N'-diacetic acid, and the salts and esters thereof.