JP2013500294A - Method for producing radiolabeled carboxylate - Google Patents

Abstract

  The present invention relates to a method for producing a radiolabeled carboxylate, wherein at least one precursor molecule of the carboxylate is prepared in a solvent comprising a conductive salt and at least one species comprising radiolabeled carbon dioxide. The reactant is fed into a solvent, the precursor molecule reacts electrochemically with the radiolabeled carbon dioxide to form a radiolabeled carboxylate, and when reacting the precursor molecule, the radiolabeled carbon dioxide is It is completely dissolved in the solvent. The invention further relates to the use of radiolabeled carbon dioxide (carbon dioxide is completely dissolved in the solvent during synthesis) to electrochemically synthesize radiolabeled carboxylates, and radiolabeling It relates to the use of microstructures for the electrochemical synthesis of carboxylated carboxylates (reacting with radiolabeled carbon dioxide).

Description

  The present invention relates to the technical field of radiolabeled carbon compounds. In particular, the present invention relates to a process for producing radiolabeled carboxylates and the use of radiolabeled carbon dioxide and microelectrodes for the electrochemical synthesis of radiolabeled carboxylates.

  Positron emission tomography (PET) is a nuclear medicine method that produces cross-sectional images of living organisms. During PET, the distribution of the radiolabeled substance, radiopharmakon, in the body is revealed, thereby illustrating the structure as well as the biochemical and physiological processes. Radiopharmaceuticals are labeled with radionuclides, radioatoms or isotopes.

  In contrast to conventional scintigraphy, PET uses a radiolabeled material that emits positron radiation. Two high-energy photons are emitted in opposite directions during the interaction event between positrons and body electrons. The principle of PET is to record these simultaneously generated photons by detectors facing each other. Using the time and space distribution of these recorded decay events, the spatial distribution of the radiopharmaceutical in the body is derived.

  PET is frequently applied in metabolic diseases, especially oncology, neurology and cardiology. Radiopharmaceuticals are enriched by many invasive tumors, and PET will be suitable, for example, for the diagnosis, staging, and progression monitoring of cancerous diseases. Similarly, PET can be used to illustrate the metabolic activity of the circulation and thus nerve and heart tissue. Similarly, PET can be used to detect areas of poor vascularization within the myocardium over time.

  The living body does not distinguish between radiopharmaceuticals and corresponding non-radioactive compounds, and radiopharmaceuticals will be metabolized as usual. Radiopharmaceutical decay allows radiopharmaceuticals to be tracked and visualized.

The most frequently used radionuclides are the radioisotopes carbon ( ¹¹ C), fluorine ( ¹⁸ F), nitrogen ( ¹³ N) and oxygen ( ¹⁵ O). These radionuclides are created by particle acceleration in the cyclotron.

The usefulness of radiopharmaceuticals is limited by the short half-life of the radionuclide, which is typically less than 2 hours. The radionuclide ¹¹ C has a particularly short half-life of only approximately 20 minutes. Undesirable decay of radioactivity begins as early as during the production of radionuclides in the cyclotron, during the production of the radiopharmaceutical, its delivery to the PET site and ultimately to the patient, and during the measurement, continue.

  In order to achieve the widest supply range (the positron emission tomography device to be supplied is located around the cyclotron), the highest possible radioactivity of the radiopharmaceutical should exist after its manufacture. This can be accomplished by producing a radiopharmaceutical from the radionuclide in the shortest possible time since the radionuclide decay is time dependent.

The main component for producing a radiopharmaceutical is a molecule that is biochemically or physiologically active in the living body and has one or more radionuclides incorporated into its chemical structure. Conventional methods utilize, for example, the route through the methylating agent ¹¹ CH ₃ I to radiolabel amines or carboxylic acids with ¹¹ C (Denutte et al., 1983; Vandersteene and Slegers, 1996). However, in this method, in order to obtain ¹¹ CH ₃ I, ¹¹ CO ₂ produced in the cyclotron must be further reacted in a two-step process with LiAlH ₄ and HI. In the third step, the radiolabeled methylating agent can finally be transferred to the drug to be labeled (pharmakon). As a result of this troublesome synthesis of radiopharmaceuticals, the high radioactivity ratio originally provided by ¹¹ CO ₂ is lost.

Significant technology has been introduced for new PET contrast agents in the field of ¹⁸ F labeling by so-called “click chemistry”. This method allows for the synthesis of radioactive contrast agents in a single step (Devaraj et al., 2009; Li et al., 2007). However, fluorine-labeled radiopharmaceuticals, such as ¹⁸ F-fluorouracil, ¹⁸ F-6-fluoro-DOPA or ¹⁸ F-fluoro-2-deoxy-D-glucose, are originally not correspondingly labeled. Therefore, it is desirable to use hydrocarbon compounds that are not chemically different from their original molecules.

European Patent Application Publication No. 0189120

Denutte et al., J Nucl Med 24, 1185-1187, 1983 Abstract for Devaraj et al., Bioconjugate Chem 20 (2), 397-401, 2009 Abstract for Li et al., Bioconjugate Chem 18 (6), 1987-1994, 2007 Abstract for Vandersteene and Slegers, Applied Radiation and Isotopes 47 (2), 201-205, 1996

  Accordingly, an object of the present invention is to provide an efficient method by which a radiolabeled hydrocarbon compound can be synthesized in a high yield within a short production time.

This purpose is
Providing at least one precursor molecule of carboxylate in a solvent comprising a conductive salt;
Introducing at least one reactant comprising radiolabeled carbon dioxide into a solvent; and electrochemically reacting precursor molecules with radiolabeled carbon dioxide to obtain a radiolabeled carboxylate. ;
Where the radiolabeled carbon dioxide is achieved by a method of producing a radiolabeled carboxylate that is completely dissolved in a solvent during the reaction of the precursor molecule.

  Furthermore, the present invention relates to the use of radiolabeled carbon dioxide for the electrochemical synthesis of radiolabeled carboxylates, wherein the carbon dioxide is completely dissolved in the solvent during the synthesis. ing.

  Furthermore, the present invention relates to the use of a microelectrode for reacting radiolabeled carbon dioxide to electrochemically synthesize radiolabeled carboxylates.

  The dependent claims contain advantageous embodiments of the invention.

  The present invention will be described in more detail below with reference to the accompanying drawings.

FIG. 3 shows electrochemical reductive carboxylation of ketones with ¹¹ CO ₂ incorporation to synthesize radiolabeled α- ¹¹ C-amino acids. FIG. 3 shows electrochemical reductive carboxylation of ketones with ¹¹ CO ₂ incorporation to synthesize radiolabeled α- ¹¹ C-hydroxy acid. FIG. 3 shows reductive carboxylation for producing amino acids by reacting imine with radiolabeled cyanide. FIG. 2 is a diagram showing two microelectrodes, a cathode 1 and an anode 3, and further their relative arrangement.

The present invention provides a method for producing a radiolabeled carboxylate, the method comprising:
Providing at least one precursor molecule of carboxylate in a solvent comprising a conductive salt;
Introducing at least one reactant comprising radiolabeled carbon dioxide into a solvent; and electrochemically reacting precursor molecules with radiolabeled carbon dioxide to obtain a radiolabeled carboxylate. ;
Where the radiolabeled carbon dioxide is completely dissolved in the solvent during the reaction of the precursor molecules.

The term “carboxylate” as used herein refers to a compound of the empirical formula R ₁ R ₂ R ₃ C (COO ⁻ ) that contains a carboxyl group. The groups R ₁ , R ₂ , R ₃ bonded to the central carbon atom can be the same or different, saturated or unsaturated, linear, branched or cyclic, aliphatic, aromatic or heteroaromatic groups, or These may be mixed. These groups are premised on not containing groups that are themselves reactive under the conditions of carboxylation according to the invention. Carboxylates include carboxylate amides, imides, anhydrides, carboxylic acid esters, carboxylic acid halides, aldehydes, ketones, amino acid salts, hydroxy acid salts, urethanes, and carboxylic acids, among others.

  The term “precursor molecule” as used herein refers to starting materials and starting compounds for carboxylate synthesis, such as, for example, imine or carbonyl compounds (see FIGS. 1-3).

  The term “conductive salt” as used herein refers to an electrolyte that dissolves in a solvent and carries an electric current.

  The term “reactant” as used herein includes chemical molecules such as carbon dioxide, cyanide, water, and ammonia, as well as protons and electrons. The introduction of the reactants into the solvent can be done in one or more steps, and the reactants can be introduced at the same time in a partial overlap or subsequently.

  The term “electrochemically” as used herein refers to a chemical reaction by electrolysis.

  The term “dissolved carbon dioxide” refers to both physically dissolved carbon dioxide and bicarbonate. The term “fully dissolved” as used herein means that no gas phase is generated in the solvent. The term likewise refers to complete saturation of the solvent with carbon dioxide. Complete dissolution can be accomplished by predissolving carbon dioxide in the solvent under very high pressure prior to the start of the reaction.

  In the process according to the invention for producing radiolabeled carboxylates, a short reaction time and thereby a short production time and even a high yield of carboxylate is achieved by completely dissolving the radiolabeled carbon dioxide. The

  As a result of complete dissolution of the carbon dioxide, its concentration in the solvent increases. Concentration gradients due to undissolved gas phase are avoided. Complete dissolution of carbon dioxide leads to better mixing and uniform concentration of carbon dioxide in the solvent. That is, as a whole, the reaction time and production time are shortened and the yield is increased.

  As a result of the short reaction time and production time, this time the loss of radiochemical yield due to spontaneous decay as a function of radionuclide time is reduced.

So far, due to the rapid radioactive decay of radioactive ¹¹ C, it has become necessary to use extremely high doses of radioactive starting materials to synthesize carboxylate radiopharmaceuticals. By shortening the reaction time by the method according to the invention, the dose of radioactive carbon used during the synthesis of the carboxylate can be reduced. This saves costs and reduces the radioactive burden of the radiochemist during the production of the radiolabeled carboxylate.

  The reaction according to the invention between precursor molecules and radiolabeled carbon dioxide is very simple and can be carried out at low equipment costs. There is no need to isolate or purify the intermediate. The method according to the invention can therefore be used as such in clinical or radiosurgery.

  The reaction according to the invention between precursor molecules and radiolabeled carbon dioxide is carried out by reductive electrochemical carboxylation via a short and rapid synthetic route. Radiolabeled carbon dioxide is incorporated into the precursor molecule during the final step of carboxylate synthesis according to the present invention, ie, only one synthesis step prior to the final carboxylate product (see FIGS. 1 and 2). Carboxylation or even labeling takes place in a single step without any other synthetic steps.

  Carboxylate synthesis using carbon dioxide is described in EP-A-0189120, where no radiolabeled carbon dioxide is used. Similarly, gaseous carbon dioxide is used there rather than fully dissolved carbon dioxide, and in EP-A-0189120, the yield is lower and the reaction time is longer. EP-A-0189120 does not relate to the production of radiolabeled carboxylates, and these disadvantages are less serious because non-radioactive carboxylates do not decay as a function of time and are stable. Furthermore, the amount of starting material used in EP-A-0189120 is not a critical factor since no radioactive exposure occurs.

  In a preferred embodiment, the carboxylate is an α-hydroxy acid salt and / or an α-amino acid salt. The prefix “α-” refers to the position of the carboxyl group on the α-carbon atom to which the hydroxyl or amino group is also attached.

  α-Hydroxy acid salts are synthesized directly from ketones or aldehydes in a single-step reaction involving the incorporation of radiolabeled carbon dioxide (FIG. 1). It is therefore a very rapid and simple reaction with a low loss of radiochemical yield due to spontaneous decay. It is therefore possible to reduce the dose of radioactive carbon dioxide used and therefore reduce the radiation exposure.

  Precursor molecules for producing α-amino acid salts are synthesized by the first part of the established Strecker reaction (FIGS. 1 and 3). The α-amino acid salt can be synthesized in a higher yield than the α-hydroxy acid salt by the method according to the present invention. α-Amino acid salts, like α-hydroxy acid salts and their acids, are physiologically important molecules that exist extensively during metabolism and are conventional PET biomarkers with diverse uses. There will be.

In further embodiments, the precursor molecule comprises a ketimine, aldimine, ketone, aldehyde, and / or ions thereof. Aldimine has the formula R ₁ HCNR ₂ , ketimine has the formula R ₁ R ₂ CNR ₃ , ketone has the formula R ₁ R ₂ CO, and aldehyde has the formula R ₁ HCO. An example of a ketimine ion is an iminium cation (FIG. 3). The groups R ₁ , R ₂ and R ₃ can be the same or different aromatic, heteroaromatic and aliphatic groups. Aliphatic groups include acyclic branched and unbranched, cyclic and alicyclic saturated and unsaturated carbon compounds. It is assumed that the group does not contain a group that is itself reactive under the conditions of carboxylation. These precursor molecules are cost effective, are commercially available, and can be easily produced using standard methods.

In preferred embodiments, the conductive salt is an alkali metal halide, alkaline earth metal halide, ammonium halide, alkyl, cycloalkyl, aryl ammonium salt, or quaternary ammonium salt, especially tetra (C ₁ -C ₄₎ comprises an alkyl ammonium tetrafluoroborate or tetra (C ₁ -C ₄₎ alkyl ammonium hexafluorophosphate. The groups attached to the nitrogen of the quaternary ammonium salt are the same or different aliphatic, cycloaliphatic or aromatic groups. Chlorine, bromine, iodine, tetrafluoroborate, hexafluorophosphate, p-toluenesulfonate, perchlorate, and bis (trifluoromethylsulfonimide) are quaternary ammonium salts. A preferred anion. Tetra (C ₁ ~C ₄₎ alkyl ammonium tetrafluoroborate or hexafluorophosphate is, for example, a preferred conductive salt such as tetrabutylammonium tetrafluoroborate.

  In a further embodiment, the solvent is an organic solvent. Preferred solvents are amides, nitriles, N, N-dimethylformamide (DMF), and / or open chain or cyclic ethers.

  In a further embodiment, the reactant reacts with the precursor molecule in one step to give the carboxylate. As a result, the reaction time is short and there is little loss of radioactive yield during that time.

In a further embodiment, the radiolabeled carbon dioxide is ¹¹ CO ₂ .

  In a further embodiment, carbon dioxide is introduced into the solvent under a pressure above 2 bar, preferably above 5 bar, or above 5 bar. As a result of this high pressure, carbon dioxide is completely dissolved in the solvent during the reaction of the precursor molecules.

  In a further preferred embodiment, the reaction is performed in a continuous flow reactor. Continuous flow reactors are operated in a continuous process, so that the reaction equilibrium is shifted in the direction of synthesis. This leads to high yields, high selectivity and even low concentrations of undesirable by-products.

  In a further embodiment, the reaction is performed on the microstructure. The term “microstructure” as used herein is both miniaturized units and systems in the micrometer and even nanometer range, such as microcontainers, micromixers, microelectrodes, and micrometers. It refers to a stirrer.

  The use of microstructures ensures an improved surface / volume ratio of the reaction space. The improved surface / volume ratio leads to rapid mixing of the solvent, as well as the materials present therein, effective heat and current transfer, and a short and controllable residence time. Methods that utilize microstructures can therefore be operated more efficiently, leading to shorter reaction times and higher yields.

  The very good controllability of the synthesis on the microstructures and the low amount of health-sensitive solvents and toxic reactants, especially radiopharmaceuticals present therein, lead to high operational safety. The microstructure used during the process of the present invention is therefore the radiation burden, as well as the radiation chemist's exposure during the synthesis of radiolabeled carboxylates with substances that endanger health. ).

  In the process according to the invention for producing radiolabeled carboxylates, short reaction times and thus short production times and even high yields of carboxylates are achieved by carboxylation carried out on the microstructures. As a result of the short reaction and production time, the loss of radiochemical yield due to spontaneous decay as a function of radionuclide time is reduced. Thus, the amount of radionuclide used during the synthesis of the radiolabeled carboxylate can be reduced, resulting in cost savings and reduced exposure to the radiochemist during synthesis.

  In a further embodiment, the microstructure includes at least one microelectrode.

  During carboxylation using carbon dioxide, the reduction is performed electrochemically with the aid of a microelectrode. In this method, the sacrificial anode serves as an electron donor and exempts the use of toxic cyanide or hydrogen cyanide as an electron donor. As a result of electrochemical catalysis, the process can be operated with high yield and selectivity. Easily available compounds such as aldehydes or ketones serve as precursors.

  The microelectrode includes a microanode or a microcathode. The anode material is a soluble metal, especially aluminum, magnesium, zinc, copper or alloys thereof, with aluminum and magnesium being most preferred. Preferred cathode materials are conductive materials such as conductive carbon materials, such as graphite, carbon fiber webs, and glassy carbon, as well as nickel and magnesium, with magnesium being most preferred. Particularly preferred combinations of anode and cathode are magnesium-magnesium and magnesium-carbon combinations.

  Due to their geometric shape, the microelectrodes can be placed close to each other. As a result of spatial proximity, the electric field strength will increase for the same voltage and be able to act at a lower voltage for the same electric field strength.

  The potential difference between the microelectrodes depends on the reacting molecule and can be verified experimentally by analytical methods. Electrolysis can be operated at a constant current between microelectrodes, but the potentiostatic method is preferred because of the small amounts and volumes of solvent, conductive salt, reactants, and precursor molecules.

  In a further embodiment, the microstructure includes two microelectrodes disposed in an undivided space. The undivided electrode space has the advantage of increased product selectivity as a result of salt formation with the dissolved sacrificial anode cations. Salt formation protects against unwanted secondary reactions, such as reducing precursor molecules to give pinacol derivatives. Furthermore, the ohmic resistance is not increased as a result of the separation membrane in the undivided space.

  In a further preferred embodiment, the microelectrode comprises a coating, a tubular module, such as a microcapillary, a linear element, such as a wire, a two-dimensional lattice, a two-dimensional surface or a three-dimensional mesh. As a result of these electrode variants, the surface / volume ratio is further improved.

  In a particularly preferred embodiment, the tubular module is the cathode 1 and the linear element is the anode 3. The anode 3 is disposed at the center inside the cathode 1. The cathode 1 and the anode 3 are arranged relative to each other so that the longitudinal direction of the cathode 1 and the longitudinal direction of the anode 3 run in parallel to each other (FIG. 4).

  In a particularly preferred embodiment, the two-dimensional surface is in each case an anode and a cathode arranged on opposite walls of a rectangular microstructure. The arrangement of the two-dimensional anode and cathode on the opposing walls of the flat rectangular microstructure advantageously combines a uniform electric field in the electrode space with the preferred flow rate of the reactants, so that the electrochemical reaction is It is constructed more efficiently and the reaction time is shortened. Furthermore, the yield increases with simultaneous minimization of secondary reactions due to the uniform residence time in this microstructure.

  In an especially preferred embodiment, the reaction temperature is 20 ° C to 30 ° C. In a further embodiment, the concentration of precursor molecules in the solvent is 0.1M.

  In a further embodiment, the method further comprises the step of acidic hydrolysis of at least one carboxyl group of the carboxylate. For example, as a result of acidic hydrolysis with hydrochloric acid, the corresponding carboxylic acid is obtained with the addition of a proton from the carboxylate, the corresponding amino acid is obtained from the amino acid salt, and the corresponding hydroxy acid is obtained from the hydroxy acid salt. can get.

  Furthermore, the method according to the invention comprises the step of isolating the carboxylic acid from the solvent. Isolation is preferably performed by precipitation, filtration, evaporation, preparative chromatography, and / or decantation, and similarly includes separation from conductive salts and desired and undesirable by-products. Precipitation is performed using, for example, a low polarity solvent. In a further step, the acid functionality of the carboxylic acid can be derivatized using, for example, methanol and sulfuric acid. In a further step, the carboxylic acid can also be analyzed, for example by chromatography, especially gas chromatography.

Furthermore, the present invention relates to a method for producing a radiolabeled carboxylate, which method comprises:
Providing at least one precursor molecule in a solvent;
Adding at least one reactant comprising a radiolabeled cyanide to a solvent; and reacting a precursor molecule with the reactant to obtain a radiolabeled carboxylate;
Where the reaction is performed on the microstructure.

  FIG. 3 shows reductive carboxylation using cyanide as an example.

  Furthermore, the present invention relates to the use of radiolabeled carbon dioxide for the electrochemical synthesis of radiolabeled carboxylates, wherein the carbon dioxide is completely dissolved in the solvent during the synthesis. Has been.

  Furthermore, the present invention relates to the use of a microelectrode for electrochemically synthesizing radiolabeled carboxylates by reacting radiolabeled carbon dioxide.

  The variations and embodiments described above relating to the first subject of the invention are also related to other subjects of the invention.

  The schematic diagrams in FIGS. 1-4 show selected examples of carboxylation according to the present invention.

FIG. 1 shows the synthesis of α-amino acids by reductive electrochemical carboxylation. The precursor molecule, an iminium cation of formula (R ₁ R ₂ C (NH ₂ )) ⁺ is synthesized by, for example, Strecker synthesis with removal of water using ammonia and hydrogen from ketone R ₁ R ₂ CO . The iminium cation is reduced by incorporating two electrons and reacted by adding radiolabeled carbon dioxide to give the amino acid salt R ₁ R ₂ (H ₂ N) ¹¹ C (COO ⁻ ). As a result, the carbon atom of the carboxyl group becomes radiolabeled. The carboxyl group is further hydrolyzed by addition of protons, and the amino acid salt reacts to obtain an amino acid. In the case of this synthesis, it is possible to dispense with protecting the acidic proton.

FIG. 2 shows the synthesis of α-hydroxy acids by reductive electrochemical carboxylation. The precursor molecule is a ketone R ₁ R ₂ CO, which is reduced by taking two electrons and reacting by adding radiolabeled carbon dioxide to produce an α-hydroxy acid salt R ₁ R ₂ HO ¹¹ C (COO ⁻ ) is obtained. The α-hydroxy acid salt is hydrolyzed to an α-hydroxy acid by adding a proton.

FIG. 3 shows the synthesis of radiolabeled nitrile from imine with incorporation of protons as well as radiolabeled cyanide ¹¹ CN ⁻ . The radiolabeled nitrile can be hydrolyzed to provide additional amino acids.

  FIG. 4 shows an embodiment of an electrochemical microcontinuous flow reactor having a capillary tube, and the inner wall of the capillary tube constitutes the cathode 1. Furthermore, the microcontinuous flow reactor has an anode 3 (wire) placed centrally in the capillary.

Claims (19)

A method for producing a radiolabeled carboxylate comprising:
Providing at least one precursor molecule of carboxylate in a solvent comprising a conductive salt;
Introducing at least one reactant comprising radiolabeled carbon dioxide into a solvent; and. Reacting the precursor molecule electrochemically with the radiolabeled carbon dioxide to obtain a radiolabeled carboxylate. Step;
Wherein the radiolabeled carbon dioxide is completely dissolved in the solvent during the reaction of the precursor molecule.   The method according to claim 1, characterized in that the carboxylate is an α-hydroxylate and / or an α-amino acid salt.   3. The method according to claim 1 or 2, characterized in that the precursor molecule is selected from the group consisting of ketimines, aldimines, ketones, aldehydes and their ions. Conductive salts, alkali metal halide, alkaline earth metal halides, ammonium halides, alkyl -, cycloalkyl -, aryl ammonium salts and quaternary ammonium salts, inter alia, tetra (C ₁ ~C ₄₎ alkyl characterized in that it is selected from tetrafluoroborate and tetra (C ₁ -C ₄₎ group consisting of alkyl ammonium hexafluorophosphate the method according to any one of claims 1 to 3.   5. Solvent according to any one of claims 1 to 4, characterized in that the solvent is an organic solvent specifically selected from the group consisting of amides, nitriles, N, N-dimethylformamide, and open-chain and even cyclic ethers. the method of.   6. A process according to any one of claims 1 to 5, characterized in that the reactant is reacted with the precursor molecule in one step to obtain the carboxylate. Wherein the radiolabeled carbon dioxide is ¹¹ CO _2, the method according to any one of claims 1 to 6.   8. Process according to any one of claims 1 to 7, characterized in that carbon dioxide is introduced into the solvent under a pressure above 2 bar, preferably above 5 bar or above 5 bar.   9. Process according to any one of claims 1 to 8, characterized in that the reaction is carried out in a continuous flow reactor.   10. A method according to any one of claims 1 to 9, characterized in that the reaction is carried out on a microstructure.   11. A method according to claim 10, characterized in that the microstructure comprises at least one microelectrode.   12. A method according to claim 10 or 11, characterized in that the microstructure comprises two microelectrodes arranged in an undivided space.   13. The microstructure according to any one of claims 10 to 12, characterized in that the microstructure is selected from the group consisting of a coating, a tubular module, a linear element, a two-dimensional lattice, a two-dimensional surface, and a three-dimensional mesh. The method described.   The tubular module is the cathode (1), the linear element is the anode (3) disposed in the center inside the cathode (1), and the cathode (1) and the anode (3) are the cathode (1). 14. The method according to claim 13, characterized in that the longitudinal direction of the anode and the longitudinal direction of the anode (3) are arranged relative to each other such that they extend parallel to each other.   14. A method according to claim 13, characterized in that the two-dimensional surface is in each case an anode and a cathode arranged on opposite walls of a rectangular microstructure.   16. The method according to any one of claims 1 to 15, further comprising the step of acidic hydrolysis of at least one carboxyl group of the carboxylate.   17. The method according to any one of claims 1 to 16, further comprising isolating the carboxylic acid from the solvent.   Use of radiolabeled carbon dioxide for electrochemical synthesis of radiolabeled carboxylates, characterized in that the carbon dioxide is completely dissolved in the solvent during the synthesis.   Use of a microelectrode for electrochemical synthesis of radiolabeled carboxylates, characterized by reacting radiolabeled carbon dioxide.

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