Nihon Medi-physics Company, Limited

Hokkaido University

Soichi Nakamura

Daisaku Nakamura

Akio Hayashi

Masahito Toyama

Toshiyuki Shinmura

Yuji Kuge

Masato Kiriu

Manabu Node

Emi Kaneko

Shinji Tokunaga

Norifumi Abo

A simple method for producing a clinically applicable radiopharmaceutical composition containing 1-(2,2-dihydroxymethyl-3-[F]fluoropropyl)-2-nitroimidazole ([F]DiFA) or a salt thereof as an active ingredient, is provided which includes a synthesis step of obtaining a crude product of [F]DiFA from a labeling precursor compound for [F]DiFA; and a purification step of purifying the crude product, in which the purification step includes purifying [F]DiFA using two or more different types of reverse phase solid phase extraction cartridges.

Method for producing radiopharmaceutical composition

A method for producing a radioactive diagnostic imaging agent containing a radioactivefluorine-labeled organic compound represented by the following formula (1): as an effective ingredient in which radiolysis of the effective ingredient is inhibited, involves providing a solution containing the radioactivefluorine-labeled organic compound represented by the above formula (1), adding an acid to the solution obtained in the first step in an amount sufficient for the solution to be kept within a pH of 2.0-5.9 in the following third step, and diluting the solution obtained in the second step in order to adjust the solution to a desired radioactive concentration within a pH of 2.0-5.9.

Method for production of radiation diagnostic imaging agent

A method for producing a radioactive diagnostic imaging agent which contains a radioactive halogen-labeled amino acid compound as an effective ingredient and has a composition that can inhibit radiolysis of the effective ingredient, thereby further improving stability, is provided. Disclosed is a method for producing a radioactive diagnostic imaging agent, comprising a solution preparation step of preparing a solution containing a radioactive halogen-labeled amino acid compound, and a dilution step of diluting the solution containing the radioactive fluorine-labeled organic compound in order to adjust radioactive concentration thereof, which further comprises an acid addition step of adding an acid to the solution containing the radioactive fluorine-labeled organic compound, after the solution preparation step and before the dilution step, wherein the acid is added in the acid addition step in an amount sufficient to adjust the pH of the solution resulting from the dilution step to 2.0-5.9, for example, in an amount corresponding to 0.40-2.8 mmol per 1 L of the solution resulting from the dilution step.

An optically active tropinonemonocarboxylic acid ester derivative useful as an intermediate for synthesis of optically active tropane derivatives was obtained by reacting succindialdehyde with an organic amine and acetonedicarboxylic acid ester to obtain a tropinonedicarboxylic acid ester derivative, and then subjecting this derivative to enzyme-catalyzed asymmetric dealkoxy-carbonylation. Since anhydroecgonine methyl ester derived from the optically active tropinone-monocarboxylic acid ester derivative by reduction and dehydration had the same direction of optical rotation as in the case of anhydroecgonine methyl ester obtained from natural cocaine, it was proved that the obtained optically active tropinonemonocarboxylic acid ester derivative had the same absolute configuration as that of natural cocaine. The yield of the optically active tropinonemonocarboxylic acid ester derivative from the asymmetric dealkoxycarbonylation was 30 to 50 mol %, and its optical purity was 70 to 97% ee. In addition, it was found that a crystalline optically active anhydroecgonine carboxylic acid ester derivative can be obtained by reducing and then dehydrating the optically active tropinonemonocarboxylic acid ester derivative and that its optical purity can easily be increased by recrystallization.

Process for producing optically active tropinonemonocarboxylic acid derivative

Growing community of inventors

Sodegaura, Japan

Soichi Nakamura