An aqueous pharmaceutical composition including compound having the formula of tetragadolinium[4,10-bis(carboxylatomethyl)-7-{-3,6,12,15-tetraoxo-16-[4,7,10-tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]-9,9-bis({[({2-[4,7,10-tris(carboxylatomethyl)-1,4,7,10- tetraazacyclododecan-1-yl]propanoyl}amino)acetyl]amino}methyl)-4,7,11,14-tetraazaheptadecan-2-yl}-1,4,7,10-tetraazacyclododecan-1-yl]acetate wherein the stereochemistry at the chiral carbon of the four alanine substituents is selected from the group consisting of RRRR, SSSS, RSSS, RRSS, and RRRS stereoisomers, and racemic and diastereomeric mixtures of any thereof, or a tautomer, a hydrate, a solvate, or a salt thereof, or a mixture of same is described. The compounds may be used as an MRI contrast imaging agent.

A compound comprising a prostate specific membrane antigen (PSMA)-targeting moiety of the following formula or of a salt or a solvate thereof. R.sup.0 is O or S. Each of R.sup.1a, R.sup.1b and R.sup.1c may be —CO.sub.2H, —SO.sub.2H, —SO.sub.3H, —PO.sub.2H, or —PO.sub.3H.sub.2, for example. R.sup.2 may be methylene or a derivative thereof, propylene or a derivative thereof, or a derivative of ethylene, optionally substituted. R.sup.3 is a linker. When the PSMA-targeting moiety is linked to a radiolabeling group, the compound may be used as an imaging agent or therapeutic agent for PSMA-expressing diseases/conditions.

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In a compound of the present invention, in a macroscopic view of a chemical structure thereof, a chelating moiety is located at the center of the structure, an atomic group containing an albumin binding moiety binds to one side of the chelating moiety, and an atomic group containing a target molecule binding moiety binds to the other side of the chelating moiety. The chelating moiety is also preferably DOTA or a derivative thereof. The target molecule binding moiety preferably has a structure to bind to a target molecule expressed in a cancer tissue. The present invention also provides a radioactive labeled compound in which the compound is coordinated to a radioactive metal ion.

Disclosed is an advancement in provoked chemical cleavage. Thereby the invention provides the use of a diene as a chemically cleavable group attached to a Construct, and the use of a dienophile to provoke the release of the Construct by allowing the diene to react with a dienophile capable of undergoing an inverse electron demand Diels Alder reaction with the diene. The invention includes a kit for releasing a Construct C.sup.A bound to a Trigger T.sup.R, the kit having a tetrazine and a dienophile, wherein the Trigger is the tetrazine. The invention also includes the use of the formation of a pyridazine by reacting a tetrazine having a Construct C.sup.A bound thereto and a dienophile, as a chemical tool for the release, in a chemical, biological or physiological environment, of the Construct.

A hydrolysis method for tert-butyl ester in gadolinium-based contrast agent comprises hydrolyzing the tert-butyl ester with a catalyst. The preparation method of the catalyst comprises the following steps: subjecting zirconia and titanium tetrachloride to reaction in the presence of sulfuric acid and water at 60° C. to 90° C. until solids are dissolved, adding silica to perform reaction for 1 to 5 h, filtering to obtain solids, washing and calcining the solids. This hydrolysis method does not introduce other substances that are difficult to remove, such as acids, and provides high hydrolysis efficiency and high purity of the obtained product.

A hydrolysis method for tert-butyl ester in gadolinium-based contrast agent comprises hydrolyzing the tert-butyl ester with a catalyst. The preparation method of the catalyst comprises the following steps: subjecting zirconia and titanium tetrachloride to reaction in the presence of sulfuric acid and water at 60° C. to 90° C. until solids are dissolved, adding silica to perform reaction for 1 to 5 h, filtering to obtain solids, washing and calcining the solids. This hydrolysis method does not introduce other substances that are difficult to remove, such as acids, and provides high hydrolysis efficiency and high purity of the obtained product.

The present invention relates to a compound of formula 1 and a pharmaceutical composition containing same. This compound may be useful as: a therapeutic agent for degenerative brain diseases including dementia or cranial nerve diseases and developmental disorders caused by neural cell damage, various degenerative neural diseases, ischemic nerve diseases, or neural damage diseases; a learning ability-improving agent; and a cognitive function-improving agent. [Formula 1] in formula 1 above, B represents a part derived from retinoic acid.

The present invention relates to a compound of formula 1 and a pharmaceutical composition containing same. This compound may be useful as: a therapeutic agent for degenerative brain diseases including dementia or cranial nerve diseases and developmental disorders caused by neural cell damage, various degenerative neural diseases, ischemic nerve diseases, or neural damage diseases; a learning ability-improving agent; and a cognitive function-improving agent. [Formula 1] in formula 1 above, B represents a part derived from retinoic acid.

Described herein is a contrast agent for administration to a subject. The contrast agent includes a targeting portion that includes a hydrazide functional group; a metal ion bound to a metal-complexable portion; and a linker joining the targeting portion and the metal-complexable portion of the contrast agent. The portion that is not bound to a metal ion localizes the contrast agent to necrotic tissue in the subject.

The present disclosure relates to a novel method for preparing high-purity gadobutrol. The present disclosure can be easily applied to a large scale production because purity of intermediate can be managed via simple and mild process and accordingly, high-purity or ultra high-purity gadobutrol that has higher purity than previous gadobutrol can be prepared in high yield therethrough.