Method of preparing a chlorinated, brominated, radiobrominated, iodinated and/or radioiodinated, aromatic or heteroaromatic compound, as well as a kit for preparing a diagnostic composition on the basis of this compound

Claim 3

A method as claimed in Claim 1 of preparing a brominated, radiobrominated, iodinated or radioiodinated aromatic or heteroaromatic compound, in which the (hetero)-aromatic nucleus is a benzene nucleus, a naphthalene nucleus, a pyridine nucleus, a pyrimidine nucleus, a quinoline nucleus or an indole nucleus which comprises one or more additional substituents, by reacting the corresponding halogenated or diazonium-substituted compound in the presence of a water-soluble, acid and of copper ions as a catalyst with a likewise water-soluble bromide, radiobromide, iodide or radioiodide, characterized in that the reaction is carried out in the presence of one or more reduction agents, which are stable in acid medium, in a quantity exceeding the quantity of catalyst.

Claim 4

A method as claimed in Claim 2 of preparing iodine--containing contrast media, for example iophendylate and other ones on the basis of 2-, 2,4- or 2,4,6-substituted 1,3,5-triiodobenzene, by reacting the corresponding brominated or diazonium-substituted compound in the presence of a water-soluble acid and of copper ions as a catalyst with a likewise water-soluble iodide, characterized in that the reaction is carried out in the presence of one or more reduction agents, which are stable in acid medium, in a quantity exceeding the quantity of catalyst.

Claim 5

A method as claimed in Claim 2 of preparing starting substances for radioiodinated diagnostics, which starting substances are selected from the group consisting of o-iodohippuric acid or salts thereof, iodoamphetamine or derivatives thereof, iodo-ω-phenyl fatty acids or salts thereof and rose bengal, by reacting the corresponding brominated or diazonium-substituted compound in the presence of a water-soluble acid and of copper ions as a catalyst with a likewise water-soluble iodide, characterized in that the reaction is carried out in the presence of one or more reduction agents, stable in acid medium, in a quantity exceeding the quantity of catalyst.

Claim 6

A method as claimed in Claim 2 of preparing radio- iodinated diagnostics selected from the group consisting of radioiodinated o-iodohippuric acid or salts thereof, iodoamphetamine or derivatives thereof, iodo-Ú-phenyl fatty acids or salts thereof, rose bengal, N-iodoquinolyl-N'--N'-dimethylpropanediamine, N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine, p-iodosulphonamide, N-iodophenylsulphonyl-N'-ethyl urea, gliben- clamide, 3-iodo-4-aminophenylethylamine, N,N-dimethyliodo- benzylamine, substituted or non-substituted iodopyridines or iodopyridineoxides, mono- and triiodobenzoic acid, N--[3-acetyl-4-(3-isopropylamino-2-hydroxy)propoxyphenyl]-iodobenzamide, iodinated indocyanine green, iodinated hy- droxybenzylpindolol, iodinated thiouracil, iodinated estradiol, halogenated phenothiazines, halogenated benzodiazepines, halogenated metyrapone, halogenated butyrophenone derivatives, halogenated dibenzazepines, halogenated thyroid gland hormones such as 3,3'-diiodothyrosine, 3,3',5--triiodothyrosine and 3,3',5,5'-tetraiodothyrosine, halogenated benzylguanidine, iodoantipyrine, and iodine-containing contrast media, for example iophendylate and other ones on the basis of 2-,2,4- or 2,4,6-substituted 1,3,5--triiodobenzene, by reacting the corresponding non-labelled bromine or iodine-substituted compound in the presence of a water-soluble acid and of copper ions as a catalyst with a likewise water-soluble radioactive iodide, characterized in that the reaction is carried out in the presence of one or more reduction agents, which are stable in acid medium, in a quantity exceeding the quantity of catalyst.

Claim 7

A method as claimed in Claim 5, characterized in t at sodium iodide or potassium iodide labelled with iodine-123 or iodine-131 is used as a radioactive iodide.

Claim 10

A method as claimed in Claim 8 of preparing radio- iodinated o-iodohippuric acid or salts thereof, iodoam- phetamine or derivatives thereof, or iodo-ω-phenyl fatty acids or salts thereof, by reacting the corresponding non--adioactive bromine or iodine-substituted compound in the presence of a water-soluble acid and of copper ions as a catalyst with a likewise water-soluble radioactive iodide, characterized in that the reaction is carried out in the presence of ascorbic acid as a reduction agent.

Claim 15

A composition suitable for diagnostic examination, which comprises, in addition to a pharmaceutically acceptable formulation liquid and/or one or more auxiliary substances, a iodine-containing contrast medium, characterized in that the composition comprises a contrast medium prepared according to any of the Claims 3, 7, 8, 11 and 12.

Claim 16

14, A composition, suitable for diagnostic examination, which comprises, in addition to a pharmaceutically acceptable formulation liquid and/or one or more auxiliary substances, a radioiodinated diagnostic, characterized in that the composition comprises a diagnostic prepared according to any of the Claims 1, 2 and 5-12.

Claim 18

An equipment for carrying out the method as claimed in claim 15, characterized in that the equipment comprises (a) at least one supply syringe, provided with a cylindrical barrel for accomodating a formulation liquid, to which barrel a hollow needle is sealingly connected and in which barrel a plunger is movably positioned, the cylindrical side-wall of said barrel being provided with at least one aperture in such distance from the attached needle, that the formulation liquid to be accomodated in the barrel can be separated from the aperture in the barrel wall by means of the plunger, but that by withdrawing the plunger said aperture can allow said formulation liquid to communicate with the atmospheric pressure outside the syringe, (b) a vial for accomodating a radiodiagnostic containing subtance, which vial is sealingly closed with a pierceable stopper, and (c) an injection syringe, provided with a cylindrical barrel for accomodating an injectable composition, to which barrel a hollow needle is sealingly connected, if desired, through an intermediately positioned sterilizing filter means, the needle having a length sufficient for reaching the bottom of the vial after having pierced the stopper of said vial, and in which barrel a plunger is movably positioned.

Claim 19

A syringe for an equipment as claimed in Claim 16, provided with a cylindrical-barrel for accomodating a formulation liquid, to which barrel a hollow needle is sealingly connected and in which barrel a plunger is novably positioned, characterized in that the cylindrical side-wall of the barrel is provided with at least one aperture in such distance from the attached needle, that the formulation liquid to be accomodated in the barrel can be separated from the aperture in the barrel wall by means of the plunger, but that by withdrawing the plunger said aperture can allow said formulation liquid to communicate with the atmospheric pressure outside the syringe.

Claim 20

A kit for preparing a composition suitable for radiodiagnostic examination, comprising a bromine- or iodine-substituted aromatic or heteroaromatic compound, in which the (hetero)aromatic nucleus optionally comprises one or more additional substituents, a water-soluble acid, a copper salt and optionally a pharmaceutically acceptable formulation liquid and/or auxiliary substances, characterized in that the kit comprises in addition one or more reduction agents, which are stable in acid medium, and instructions for use stipulating that the radioactive diagnostic can be prepared by using the method as claimed in any of the Claims 1, 2, 5-9, 11 and 12.

Claim 21

A kit as claimed in Claim 18, characterized in that the kit comprises as a iodine-containing compound one of the compounds as claimed in Claim 3 or 4.

Claim 22

A kit as claimed in Claim 18 or 19, characterized in that the kit comprises as a reduction agent a reduction agent as claimed in Claim 7 or 8.

Claim 23

A kit for preparing a composition suitable for radiodiagnostic examination, comprising o-iodohippuric acid or a salt thereof, and optionally a pharmaceutically acceptable formulation liquid and/or auxiliary substances, characterized in that the kit moreover comprises ascorbic acid as a reduction agent and instructions for use stipulating that the radioactive diagnostic can be prepared by using the method as claimed in Claim 10.