A PSMA-targeting conjugate or a pharmaceutically acceptable salt which may be used either for preparing a radiopharmaceutical or, once labeled with a radionuclide, as a radiopharmaceutical. The conjugate is of formula (I): A1-L1-Ch-L2-A2 (I) wherein: Ch is a chelator, L1 and L2, identical or different, are a linker whereas A1 and A2, identical or different, are a urea-based PSMA ligand.
A method for preparing one or more generators with a high radium-228 content from an aqueous solution comprising thorium-232 and radium-228. The generator(s) can be used, in particular, for producing thorium-228, from which radium-224, then lead-212 and bismuth-212 can be obtained. The method and the generator(s) so prepared are therefore applicable, in particular, in the manufacture of radiopharmaceuticals made from lead-212 or bismuth-212, which can be used in nuclear medicine and, in particular, in targeted alpha radiotherapy for the treatment of cancers.
G21G 1/00 - Dispositions pour la conversion des éléments chimiques par rayonnement électromagnétique, radiations corpusculaires ou bombardement par des particules, p.ex. production d'isotopes radioactifs
3.
METHOD FOR TRANSFERRING A RADIOISOTOPE BETWEEN TWO STATIONARY PHASES CONTAINED IN TWO CHROMATOGRAPHY COLUMNS
A method for transferring a radioisotope which is fixed on a first stationary phase contained in a first chromatography column to a second stationary phase contained in a second chromatography column, to fix the radioisotope on the second stationary phase, wherein the radioisotope is selected from the radioactive isotopes of thorium, radium, lead, bismuth and uranium, the method comprising at least the following steps: a) eluting the radioisotope from the first stationary phase with an aqueous solution A1 comprising a citric acid salt as an agent complexing the radioisotope, whereby an aqueous solution A2 which comprises citrate complexes of the radioisotope is obtained; b) dissociating the citrate complexes of the radioisotope present in the aqueous solution A2 by modifying the pH of the aqueous solution A2, whereby an aqueous solution A3 comprising the decomplexed radioisotope is obtained; c) loading the second stationary phase with the aqueous solution A3; and d) washing at least one the second stationary phase with an aqueous solution A4.
B01D 15/18 - Adsorption sélective, p.ex. chromatographie caractérisée par des caractéristiques de structure ou de fonctionnement relatives aux différents types d'écoulement
B01D 15/38 - Adsorption sélective, p.ex. chromatographie caractérisée par le mécanisme de séparation impliquant une interaction spécifique non couverte par un ou plusieurs des groupes , p.ex. chromatographie d'affinité, chromatographie d'échange par ligand ou chromatographie chirale
4.
CONJUGATE OR ITS SALT COMPRISING A GASTRIN-RELEASING PEPTIDE RECEPTOR ANTAGONIST AND USES THEREOF
A conjugate or a pharmaceutically acceptable salt thereof, the conjugate being of formula: C-L-A, wherein C is a chelator, L is a linker covalently bound to the chelator and A is a Gastrin-releasing peptide receptor antagonist covalently bound to the linker, wherein: the chelator is of formula:
A conjugate or a pharmaceutically acceptable salt thereof, the conjugate being of formula: C-L-A, wherein C is a chelator, L is a linker covalently bound to the chelator and A is a Gastrin-releasing peptide receptor antagonist covalently bound to the linker, wherein: the chelator is of formula:
A conjugate or a pharmaceutically acceptable salt thereof, the conjugate being of formula: C-L-A, wherein C is a chelator, L is a linker covalently bound to the chelator and A is a Gastrin-releasing peptide receptor antagonist covalently bound to the linker, wherein: the chelator is of formula:
where the dotted line represents the covalent bond to the linker; the linker is of formula: -β-Ala-β-Ala-; and the Gastrin-releasing peptide receptor antagonist has the amino acid sequence: -DPhe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2.
A process is for preparing a site-specific bioconjugated antibody of a formula (I): Ab-(Linker-Chelator)n (I). The Linker is an oligopeptide with an N-terminal end. The Chelator is a metal chelating agent. n is a Chelator-to antibody ratio (CAR), wherein 0
A method for producing lead-212 of very high radiological purity from an aqueous solution comprising thorium-228 and daughters thereof. Manufacture of radiopharmaceuticals based on lead-212, which are useful in nuclear medicine and, in particular, in targeted alpha radiation therapy for the treatment of cancers.
G21G 1/00 - Dispositions pour la conversion des éléments chimiques par rayonnement électromagnétique, radiations corpusculaires ou bombardement par des particules, p.ex. production d'isotopes radioactifs
B01D 15/18 - Adsorption sélective, p.ex. chromatographie caractérisée par des caractéristiques de structure ou de fonctionnement relatives aux différents types d'écoulement
B01D 15/16 - Adsorption sélective, p.ex. chromatographie caractérisée par des caractéristiques de structure ou de fonctionnement relatives au conditionnement du fluide vecteur
B01D 15/26 - Adsorption sélective, p.ex. chromatographie caractérisée par le mécanisme de séparation
7.
METHOD FOR PREPARING AT LEAST ONE GENERATOR WITH A HIGH RADIUM-228 CONTENT
A method for preparing one or more generators with a high radium-228 content from an aqueous solution comprising thorium-232 and radium-228. The generator(s) can be used, in particular, for producing thorium-228, from which radium-224, then lead-212 and bismuth-212 can be obtained. The method and the generator(s) that it can be used to prepare are therefore applicable, in particular, in the manufacture of radiopharmaceuticals made from lead-212 or bismuth-212, which can be used in nuclear medicine and, in particular, in targeted alpha radiotherapy for the treatment of cancers.
G21G 4/08 - Sources radioactives autres que les sources de neutrons caractérisées par des aspects de leur structure spécialement adaptées aux applications médicales
G21G 1/00 - Dispositions pour la conversion des éléments chimiques par rayonnement électromagnétique, radiations corpusculaires ou bombardement par des particules, p.ex. production d'isotopes radioactifs
B01D 15/18 - Adsorption sélective, p.ex. chromatographie caractérisée par des caractéristiques de structure ou de fonctionnement relatives aux différents types d'écoulement
8.
METHOD FOR TRANSFERRING A RADIOISOTOPE BETWEEN TWO STATIONARY PHASES CONTAINED IN TWO CHROMATOGRAPHY COLUMNS
A method for transferring a radioisotope which is fixed on a first stationary phase contained in a first chromatography column to a second stationary phase contained in a second chromatography column, to fix the radioisotope on the second stationary phase, wherein the radioisotope is selected from the radioactive isotopes of thorium, radium, lead, bismuth and uranium, the method comprising at least the following steps: a) eluting the radioisotope from the first stationary phase with an aqueous solution A1 comprising an agent complexing the radioisotope, whereby an aqueous solution A2 which comprises complexes of the radioisotope is obtained; b) dissociating the complexes of the radioisotope present in the aqueous solution A2 by modifying the pH of the aqueous solution A2, whereby an aqueous solution A3 comprising the decomplexed radioisotope is obtained; c) loading the second stationary phase with the aqueous solution A3; and d) washing at least one the second stationary phase with an aqueous solution A4.
An apparatus is for the automated production of a daughter radionuclide from a parent radionuclide using a generator comprising a solid medium onto which the parent nuclide is fixed and whereby the daughter nuclide is formed by radioactive decay of the parent nuclide. The apparatus includes a fluid circuit including a chromatography column having a head port and a tail port, at least one connection port for connecting the generator to the fluid circuit, at least one inlet port for connecting fluid sources to the fluid circuit and at least one valve controlled by an electronic control unit for selectively connecting the chromatography column, the connection port and the at least one inlet port in various configurations. The various configurations include a first elution configuration for circulating an A1′ solution exiting the generator and containing the daughter radionuclide, through the chromatography column from the head port to the tail port for loading the chromatography column with the daughter radionuclide; a first washing configuration for circulating an A2 washing solution from a solution inlet through the chromatography column from the head port to the tail port; and a second washing configuration for circulating an A2′ washing solution from a solution inlet through the chromatography column from the tail port to the head port.
G21G 1/00 - Dispositions pour la conversion des éléments chimiques par rayonnement électromagnétique, radiations corpusculaires ou bombardement par des particules, p.ex. production d'isotopes radioactifs
B01D 15/20 - Adsorption sélective, p.ex. chromatographie caractérisée par des caractéristiques de structure ou de fonctionnement relatives au conditionnement de la matière adsorbante ou absorbante
B01D 15/36 - Adsorption sélective, p.ex. chromatographie caractérisée par le mécanisme de séparation impliquant une interaction ionique, p.ex. échange d'ions, paire d'ions, suppression d'ions ou exclusion d'ions
B01D 15/42 - Adsorption sélective, p.ex. chromatographie caractérisée par le mode de développement, p.ex. par déplacement ou par élution
C22B 60/02 - Obtention du thorium, de l'uranium ou des autres actinides
G21G 4/08 - Sources radioactives autres que les sources de neutrons caractérisées par des aspects de leur structure spécialement adaptées aux applications médicales
10.
Treatment of cancer cells overexpressing somatostatin receptors using ocreotide derivatives chelated to radioisotopes
A cancer targeting composition, kit, and method for treatment of cancer cells overexpressing somatostatin receptors is disclosed. The composition includes a radioisotope, a chelator, and a targeting moiety. The chelator includes a nitrogen ring structure including a tetraazacyclododecane, a triazacyclononane, and/or a tetraazabicyclo [6.6.2] hexadecane derivative. The targeting moiety includes a somatostatin receptor targeting peptide. The somatostatin receptor targeting peptide includes an octreotide derivative. The targeting moiety is chelated to the radioisotope by the chelator whereby the cancer cells are targeted for elimination.
A process for producing a daughter radionuclide from a parent radionuclide includes a) loading the parent radionuclide on a first solid medium contained in a generator and onto which the parent radionuclide is retained and whereby the daughter radionuclide is formed by radioactive decay of the parent radionuclide; b) eluting this medium with a A0 solution so as to recover a A1 solution comprising the daughter radionuclide; c) optionally adjusting the pH of the A1 solution so as to obtain a A1′ solution, d) loading this A1 or A1′ solution onto the head of a second solid medium contained in a chromatography column; e) first washing said second solid medium with a A2 solution; f) second washing said second solid medium with a A2′ solution; g) eluting the daughter radionuclide with a A3 solution. The first washing step is conducted from head to tail of the column and the second washing step and the second eluting step are conducted from tail to head of the column.
G21G 1/00 - Dispositions pour la conversion des éléments chimiques par rayonnement électromagnétique, radiations corpusculaires ou bombardement par des particules, p.ex. production d'isotopes radioactifs
B01D 15/20 - Adsorption sélective, p.ex. chromatographie caractérisée par des caractéristiques de structure ou de fonctionnement relatives au conditionnement de la matière adsorbante ou absorbante
B01D 15/36 - Adsorption sélective, p.ex. chromatographie caractérisée par le mécanisme de séparation impliquant une interaction ionique, p.ex. échange d'ions, paire d'ions, suppression d'ions ou exclusion d'ions
B01D 15/42 - Adsorption sélective, p.ex. chromatographie caractérisée par le mode de développement, p.ex. par déplacement ou par élution
C22B 60/02 - Obtention du thorium, de l'uranium ou des autres actinides
G21G 4/08 - Sources radioactives autres que les sources de neutrons caractérisées par des aspects de leur structure spécialement adaptées aux applications médicales
12.
Method and apparatus for the production of lead 212 for medical use
The invention relates to a method for preparing lead (212) for medical use. This method comprises the production of lead (212) by the decay of radium (224) in a generator comprising a solid medium to which the radium (224) is bound, followed by the extraction of the lead (212) from the generator in the form of an aqueous solution A1, characterised in that the lead (212) contained in the aqueous solution A1 is purified from the radiological and chemical impurities, also contained in said aqueous solution, by a liquid chromatography on a column. The invention also relates to an apparatus specially designed for automated implementation in a closed system of said method. It further relates to lead (212) produced by means of this method and this apparatus. Applications: manufacture of radiopharmaceuticals based on lead (212), useful in nuclear medicine for the treatment of cancers, particularly by a-radioimmunotherapy, or for medical imaging, in both humans and animals.
G21G 1/00 - Dispositions pour la conversion des éléments chimiques par rayonnement électromagnétique, radiations corpusculaires ou bombardement par des particules, p.ex. production d'isotopes radioactifs
B01D 15/42 - Adsorption sélective, p.ex. chromatographie caractérisée par le mode de développement, p.ex. par déplacement ou par élution
A61K 51/12 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo caractérisées par un aspect physique particulier, p.ex. émulsion, microcapsules, liposomes
B01D 15/12 - Adsorption sélective, p.ex. chromatographie caractérisée par des caractéristiques de structure ou de fonctionnement relatives à la préparation de l'alimentation
G21G 4/08 - Sources radioactives autres que les sources de neutrons caractérisées par des aspects de leur structure spécialement adaptées aux applications médicales
13.
Method and apparatus for the production of lead 212 for medical use
The invention relates to a method for preparing lead (212) for medical use. This method comprises the production of lead (212) by the decay of radium (224) in a generator comprising a solid medium to which the radium (224) is bound, followed by the extraction of the lead (212) from the generator in the form of an aqueous solution A1, characterized in that the lead (212) contained in the aqueous solution A1 is purified from the radiological and chemical impurities, also contained in said aqueous solution, by a liquid chromatography on a column. The invention also relates to an apparatus specially designed for automated implementation in a closed system of said method. It further relates to lead (212) produced by means of this method and this apparatus. Applications: manufacture of radiopharmaceuticals based on lead (212), useful in nuclear medicine for the treatment of cancers, particularly by a-radioimmunotherapy, or for medical imaging, in both humans and animals.
G21G 1/00 - Dispositions pour la conversion des éléments chimiques par rayonnement électromagnétique, radiations corpusculaires ou bombardement par des particules, p.ex. production d'isotopes radioactifs
A61K 51/12 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo caractérisées par un aspect physique particulier, p.ex. émulsion, microcapsules, liposomes
G21G 4/08 - Sources radioactives autres que les sources de neutrons caractérisées par des aspects de leur structure spécialement adaptées aux applications médicales
brevets
