Nihon Medi-physics Company, Limited

Tokyo Institute of Technology

Masahito Toyama

Akio Hayashi

Fumie Kurosaki

Toshiyuki Shinmura

Osamu Ito

Arinori Harano

Daisaku Nakamura

Soichi Nakamura

Emi Kaneko

Hiroshi Tanaka

Masato Kiriu

Shinji Tokunaga

Soichi Takasaki

It is intended to provide a novel amino acid organic compound which can be used as a labeling precursor compound for radioactive halogen-labeled amino acid compounds including [F]FACBC, and which prevents methanol from remaining in the radioactive halogen-labeled amino acid compounds produced therefrom. The novel amino acid organic compound is a compound represented by the following formula: wherein n is an integer of 0 or of 1 to 4; Ris an ethyl, 1-propyl or isopropyl substituent; X is a halogen substituent or a group represented by &#x2014;OR; Ris a straight-chain or branched-chain haloalkylsulfonic acid substituent with one to 10 carbon atoms, trialkylstannyl substituent with 3 to 12 carbon atoms, fluorosulfonic acid substituent or aromatic sulfonic acid substituent; and Ris a protective group.

Precursor compound of radioactive halogen-labeled organic compound

There is provided a labeling precursor compound represented by the following general formula (2): wherein Rrepresents an alkynyl group, an alkynyloxy group, an azide group, an azidoalkyl group, an arylazide group, a monocyclic or condensed polycyclic aryl group or a nitrogen-containing heterocycle; Rand Reach independently represent an alkyl group or a hydroxyalkyl group which hydroxy group may be protected with a protecting group, and n is an integer of 1 or 2; Rrepresents an alkyl group or &#x2014;CONRRwherein Rand Reach independently represent an alkyl group or a monocyclic or condensed polycyclic aryl group; and R, R, Rand Reach independently represent a hydrogen atom, an alkyl group or an alkoxy group.

Radioactive fluorine labeling precursor compound and method for manufacturing radioactive fluorine labeled compound using the same

It is intended to provide a novel amino acid organic compound which can be used as a labeling precursor compound for radioactive halogen-labeled amino acid compounds including [F]FACBC, and which prevents methanol from remaining in the radioactive halogen-labeled amino acid compounds produced therefrom. The novel amino acid organic compound is a compound represented by the following formula:  wherein n is an integer of 0 or of 1 to 4; Ris an ethyl, 1-propyl or isopropyl substituent; X is a halogen substituent or a group represented by &#x2014;OR; Ris a straight-chain or branched-chain haloalkylsulfonic acid substituent with one to 10 carbon atoms, trialkylstannyl substituent with 3 to 12 carbon atoms, fluorosulfonic acid substituent or aromatic sulfonic acid substituent; and Ris a protective group.

A composition including a radioactive fluorine-labeled amino acid compound is provided, which can be prevented from radiolysis. Disclosed is a composition which includes a solution containing a radioactive fluorine-labeled amino acid compound as an effective ingredient, in which the pH value of the solution is kept at 2.0-5.9, more preferably 2.0-4.9 in order to inhibit radiolysis. Also, it is possible to further inhibit radiolysis by adding thereto a pharmaceutical additive capable of inhibiting radiolysis, such as a sugar, a sugar alcohol and a sugar lactone, while the pH is kept at 2.0-5.9.

Radioactive diagnostic imaging agent

Unnatural amino acid radiolabeling precursor

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 process is provided for producing a labeled precursor which is useful for production of a radioactive fluorine-labeled amino acid compound. In the reaction step for introducing a leaving group to a mixture of syn-form and anti-form of FACBC, a base is allowed to present in the reaction system to produce a syn-leaving group adduct, which is unreactive with the base and is highly stable, and an anti-leaving group adduct which can react with the base to form a water-soluble compound. By employing a purification method utilizing such a difference in solubility, the syn-leaving group adduct can be separated selectively. The base may be a linear- or branched-chain primary to tertiary alkylamine having 1 to 10 carbon atoms, a nitrogen-containing heterocyclic compound with 2 to 20 carbon atoms, and a nitrogen-containing hetero aromatic compound with 2 to 20 carbon atoms.

Process for production of precursor compound for radioactive halogen-labeled organic compound

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.

A process for production of a radioactive fluorine-labeled organic compound is provided which can improve the yield of radioactive fluorination. Provided is a process in which a compound represented by the following formula (1): (wherein Ris a straight or branched alkyl chain with 1-10 carbon atoms or an aromatic substituent, Ris a straight or branched haloalkylsulfonic acid substituent with 1-10 carbon atoms, a straight or branched alkylsulfonic acid substituent with 1-10 carbon atoms, a fluorosulfonic acid substituent or an aromatic sulfonic acid substituent, and Ris a protective group) is heated under stirring in an inert organic solvent in a presence of a phase transfer catalyst,F ions and potassium ions, so as to effect labeling with a radioactive fluorine, wherein the heating temperature is 40-90&#xb0; C., and the concentration of the phase transfer catalyst in the inert organic solvent is 70 mmol/L or more. Preferably, the molar ratio of the phase transfer catalyst is 0.7 or more relative to the compound of the formula (1), and the concentration of the compound of the formula (1) in the inert organic solvent is 50 mmol/L or more.

Process for production of radioactive-fluorine-labeled organic compound

It is intended to provide a labeling precursor compound used for selectively producing radioactive halogen-substituted syn-1-amino-3-cyclobutane-carboxylic acids, and to provide a process for producing a radioactive halogen-substituted syn-1-amino-3-cyclobutane-carboxylic acid using the labeling precursor compound. A labeling precursor is used in which a phthalimide group is used as a protective group for protecting the amino group. The syn-form of the radioactive halogen-substituted 1-amino-3-cyclobutane-carboxylic acid can be selectively produced by labeling the labeling precursor with a radioactive halogen followed by deprotecting.

Organic compound and method for producing radioactive halogen-labeled organic compound using the same

A process is provided for producing [F]FACBC, which can reduce the production amount of impurities. Disclosed is a process for producing a radioactive fluorine-labeled organic compound, including a deesterification step of retaining, in a reverse-phase column, a compound represented by Formula (1): wherein Ris a linear or branched C-C-alkyl chain or an aromatic substituent, and Ris a protecting group; wherein X is sodium or potassium; and 

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Sodegaura, Japan

Masahito Toyama