Recovery of gadolinium from solutions comprising gadolinium-based contrast agents

Abstract

The invention refers to a method of separating, and thus recovering, gadolinium from a solution comprising gadolinium-based contrast agents via electrolysis of the solution, thereby dissociating gadolinium ions from the gadolinium-based contrast agents, and then by precipitating the gadolinium ions to obtain gadolinium in solid form, which can be later separated from the solution.

Description

[0001] RECOVERY OF GADOLINIUM FROM SOLUTIONS COMPRISING GADOLINIUM-BASED CONTRAST AGENTS

[0002] Technical field

[0003] The invention relates to a method for separating gadolinium from a solution comprising gadolinium-based contrast agents via electrolysis.

[0004] Background art

[0005] Gadolinium-based contrast agents (GBCAs) are extensively utilized in magnetic resonance imaging (MRI) due to their efficacy in enhancing image contrast and to their tolerability.

[0006] Gadolinium is considered a critical raw material in many countries, that is a material characterized by an economic importance and whose supply is at risk. Indeed, while demand of GBCAs is continuously growing, supply of gadolinium from natural deposits is reducing. Thus, there is a focus on the recovery of gadolinium rather than its extraction.

[0007] GBCAs are primarily excreted via urine without being metabolized, thus entering the sewage system mostly as administered. However, conventional sewage treatment plants are not set up to disinfect and remove GBCAs. Indeed, anthropogenic gadolinium has been detected even at low concentration as a contaminant of freshwater and drinking water in populated areas of developed countries with good health care systems.

[0008] Oxidation processes have been conventionally used to disinfect and remove trace substances from waters. However, GBCAs are typically very stable, whereby it has been found difficult to effectively oxidize GBCAs to obtain and recover the gadolinium complexed therein.

[0009] Cyris et al. (Environ. Sci. Technol. 2013, 47, 9942-9949) discloses the interactions of GBCAs with ozone and with -OH radicals generated by the same, which could degrade commercially available GBCAs into less stable gadolinium chelates; the latter could be subjected to transmetalation reactions, liberating toxic gadolinium ions into the environment. Accordingly, this document discloses that oxidative degradation of GBCAs is not desirable.

[0010] Birka et al. (Water Research 91 (2016) 244-250) discloses the application of oxidizing UV radiation to GBCAs, and the general high stability of GBCAs towards it.

[0011] Lozano Gutierrez et al. (Electrochimica Acta 437 (2023) 141457) discloses the attempt to use electrocatalysis to oxidize a formulation of gadoterate meglumine (gadoterate is a commercially available GBCA). Only the oxidation of the counterion (meglumine) of the complex was achieved; indeed, this document discloses that the oxidation of gadoterate meglumine, leading to the release of gadolinium ion, is a challenge. In view of the above, there is the need to provide an effective process allowing the recovery of the critical raw material gadolinium from solutions comprising GBCAs, the latter being known to be exceptionally stable, while possibly overcoming the problem of liberating toxic gadolinium ions into the environment.

[0012] Summary of the invention

[0013] The invention relates to a method as set out in claim 1.

[0014] The method of the invention advantageously allows recovering gadolinium from solutions comprising GBCAs, as it provides for oxidating the GBCAs and obtaining gadolinium in solid form, which can be then separated from the solution. Moreover, the method is effective in that it provides great recovery yields. Furthermore, since the method allows obtaining gadolinium in solid form, it avoids or reduces the issue of liberating toxic gadolinium ions into solutions.

[0015] Embodiments of the invention are set out in the dependent claims and in the detailed description of the invention.

[0016] Detailed description of the invention

[0017] In a first aspect, the invention relates to a method of separating gadolinium from a solution comprising a gadolinium-based contrast agent (GBCA) comprising the following steps: a) carrying out an electrolysis of the solution to dissociate gadolinium from the GBCA, thereby obtaining gadolinium ions; b) precipitating the gadolinium ions obtained from step a) to obtain gadolinium in solid form; and c) separating the gadolinium in solid form from the solution.

[0018] The method of the invention allows recovering gadolinium from a solution comprising GBCAs. Indeed, the method provides for the electrochemical oxidation of the GBCAs, and the following obtainment of gadolinium in solid form, which can be easily separated from the solution.

[0019] Furthermore, the method of the invention is highly reproducible, and provides good yields without using harsh chemicals or dangerous means. Indeed, as demonstrated in the experimental section, the method of the invention provides a recovery yield of recovered gadolinium of about 60% or more, preferably of 70% or more, more preferably of 75% or more, even more preferably of 80% or more, and most preferably of 85% or more, such as of 90% or more, or such as of 95% or more. Recovery yield is the percentage of the amount of gadolinium in solid form separated in step c) to the amount of gadolinium present in the solution comprising the GBCA before the electrolysis step a). Moreover, obtaining gadolinium in solid form avoids or reduces the amount of toxic gadolinium ions liberated into the environment, specifically into solutions. Indeed, according to the method of the invention, toxic gadolinium ions liberated from the electrochemical oxidation of step a) can be readily and immediately precipitated in step b), and are thus subtracted from the solution.

[0020] Step a) provides for carrying out an electrolysis of the solution comprising the GBCA. This electrolysis brings about the electrochemical oxidation of the GBCA, and allows dissociating gadolinium from the GBCA; in other words, step a) allows breaking the coordinate bond of the GBCA complex. Accordingly, step a) allows obtaining gadolinium ions, which are liberated into the solution. A further advantage of step a) is that further pollutants that may be comprised within the solution can be oxidized as well, thus reducing the overall TOC of the solution. According to an embodiment, step a) comprises electrochemically oxidizing the GBCA to dissociate gadolinium from the GBCA, thereby obtaining gadolinium ions.

[0021] Step b), which can be carried out during and / or after step a), preferably during step a), provides for precipitating the gadolinium ions obtained from step a). According to the method of the invention, this precipitation starts substantially immediately or shortly after the gadolinium ions have been obtained (step a)), providing several advantages {supra . Accordingly, step b) allows obtaining gadolinium in solid form.

[0022] Step c) provides for separating the gadolinium in solid form from the solution wherein it has been precipitated in the previous step b). Once separated, gadolinium in solid form can then be used again, eventually after treating it via conventional means.

[0023] As used herein, the term "gadolinium-based contrast agent" or "GBCA", refers to a complex comprising gadolinium ion chelated by a ligand, which can be used as contrast agent for magnetic resonance imaging (MRI). Thus, GBCA is in the form of gadolinium ion associated with a (chelating) ligand via a coordinate bond. This term also encompasses intermediates or derivatives of such complexes, including those resulting from electrochemical oxidation. According to a preferred embodiment, the gadolinium-based contrast agent is selected from the group consisting of: gadoterate, gadobutrol, gadopentetate, gadobenate, gadodiamide, gadoversetamide, gadoteridol, gadofosveset, gadoxetate, gadopiclenol, and gadoquatrane. More preferably, the gadolinium-based contrast agent is selected from the group consisting of: gadoterate, gadobutrol, gadobenate, gadoteridol, gadopiclenol, and gadoquatrane.

[0024] According to an embodiment, preferably before and / or during the electrolysis of step a), the solution comprises chloride ions. It has been found that chloride ions can improve the effectiveness of step a). According to a preferred embodiment, the amount of chloride ions comprised in the solution is 0.01 mol or higher; preferably, 0.1 mol or higher; more preferably, 1 mol or higher; even more preferably, 2 mol or higher; and most preferably, 2.5 mol or higher; such as 4 mol or higher, with respect to 1 mol of gadolinium-based contrast agent. This amount of chloride ions has been found particularly useful to improve the effectiveness of step a), that is to dissociate gadolinium from the GBCA, thereby obtaining gadolinium ions. If needed, chloride ions can be conveniently added to the solution to reach and / or maintain the ranges above by adding at least a chloride salt, such as the chloride salt selected from the group consisting of sodium chloride, potassium chloride, calcium chloride, ammonium chloride, magnesium chloride, aluminium chloride, iron(III) chloride, copper(II) chloride, zinc chloride, and barium chloride.

[0025] According to an embodiment, the solution is an aqueous solution; preferably, the solution is wastewater or urine. In view of this embodiment, the method of the invention can advantageously be carried out downstream of a production line of GBCAs, or directly into the hospitals where the administration of GBCAs occur, thus avoiding or reducing the discharge of gadolinium into sewage systems.

[0026] As used herein, the term "wastewater" refers to aqueous solutions that have been adversely affected in quality by anthropogenic influence and that originate from industrial plants involved in the manufacture of GBCAs. This includes, but is not limited to, water used in the synthesis, formulation, and cleaning processes associated with GBCA production. Such wastewater typically comprises GBCAs in various amounts.

[0027] The concentration of the GBCA comprised in the solution can vary, and can be for example of 0.0001 M or higher, preferably of 0.001 M or higher, more preferably of 0.01 or higher, even more preferably of 0.02 M or higher; and / or can be of 2 M or lower, preferably of 1 M or lower, more preferably of 0.1 M or lower. According to an embodiment, the concentration of the GBCA comprised in the solution is of 0.0001 M to 2 M, preferably of 0.001 M to 1 M, more preferably of 0.001 M to 0.1 M.

[0028] According to an embodiment, the pH of the solution during step a) is maintained at 4.5 or higher, preferably at 5 or higher, more preferably at 5.5 or higher, even more preferably at 6 or higher, most preferably at 6.5 or higher; and / or at 11 or lower, preferably at 8 or lower, more preferably at 7.5 or lower. According to an embodiment, the pH of the solution during step a) is maintained at 4.5 to 11, preferably at 5 to 11, more preferably at 5.5 to 11, and even more preferably at 6 to 11, such as at 6 to 9, or at 6 to 7.5.

[0029] According to an embodiment, step a) is carried out using an anode based on an element having an atomic number from 5 to 82, oxides thereof, and mixtures thereof; preferably, using an anode based on an element comprised within period 3 and period 5 of the periodic table, boron, lead, tantalum, platinum, iridium, oxides thereof, and mixtures thereof. According to an embodiment, step a) is carried out using an anode based on at least a transition metal. According to an embodiment, the anode is based on a material selected from the group consisting of platinum, titanium, iridium, ruthenium, tin, tantalum, antimony, lead, boron (preferably, boron doped diamond), rhodium, oxides thereof, and mixtures thereof. According to an embodiment, step a) is carried out using an anode based on at least a transition metal oxide, such as the ones selected from the group consisting of platinum oxide, titanium oxide, iridium oxide, ruthenium oxide, rhodium oxide, tantalum oxide, and mixtures thereof. These anodes have been found to be particularly suitable for carrying out the electrolysis of step a).

[0030] As used herein, the term "material-based electrode" or "electrode based on a material" when referring to any or both of the electrodes, means an electrode, e.g. the cathode and / or the anode, comprising said material (e.g. titanium, platinum, etc.) in any form (e.g. metal, oxides, etc.) which, in use ( / .e. during step a)), is exposed to the solution comprising the gadolinium-based contrast agent (GBCA).

[0031] According to an embodiment, step a) is carried out using a cathode based on an element having an atomic number from 5 to 82, oxides thereof, and mixtures thereof; preferably, using a cathode based on an element comprised within period 3 and period 5 of the periodic table, boron, lead, tantalum, platinum, iridium, oxides thereof, and mixtures thereof. According to an embodiment, step a) is carried out using a cathode based on at least a transition metal. According to an embodiment, the cathode is based on a material selected from the group consisting of platinum, titanium, iridium, ruthenium, tin, tantalum, antimony, lead, boron (preferably, boron doped diamond), rhodium, iron, nickel, oxides thereof, and mixtures thereof. Iron-based cathodes include steel-based cathodes. According to an embodiment, step a) is carried out using a cathode based on at least a transition metal oxide, such as the ones selected from the group consisting of platinum oxide, titanium oxide, iridium oxide, ruthenium oxide, rhodium oxide, tantalum oxide, nickel oxide, iron oxide, and mixtures thereof. These cathodes have been found to be particularly suitable for carrying out the electrolysis of step a).

[0032] According to an embodiment, step a) is carried out using the same anode and cathode, such as the anode and cathode based on a material mentioned above.

[0033] Step a) can be carried out within a reactor; preferably, this reactor is arranged to be an electrolytic cell. The reactor can be either undivided or divided by a permeable separator, such as a cation exchange membrane or a porous septum. Preferably, step a) is carried out within an undivided reactor.

[0034] According to an embodiment, at least steps a) and b) are carried out within the same reactor. According to another embodiment, all steps are carried out within the same reactor, and step c) provides for separating gadolinium in solid form from the solution by removing gadolinium in solid form from the reactor, or by flowing the solution out of the reactor while keeping the gadolinium in solid form within the reactor, e.g. via filtration.

[0035] Step a) of the invention can be performed in galvanostatic mode or in potentiostatic mode. When step a) is performed in galvanostatic mode, the galvanostatic conditions may vary, and can depend on e.g. surface of the anode in contact with the solution, or on the amount of solution that is electrolysed; for example, the current density can be of 0.001 A / cm2or higher; preferably, of 0.01 A / cm2or higher; more preferably, of 0.08 A / cm2or higher; even more preferably, of 0.15 A / cm2or higher; and most preferably of 1 A / cm2or higher, such as of 100 A / cm2or higher, or 1000 A / cm2or higher (which may be particularly suitable for industrial processes). When step a) is performed in potentiostatic mode, the potentiostatic conditions may vary, and can depend on several factors such as the composition of the solution; for example, the potential difference is of 1.36 V or higher, preferably of 2 V or higher.

[0036] Step a) can be advantageously carried out without controlling the temperature of the reaction, whereby a temperature increase might occur without affecting the effectiveness of the reaction.

[0037] The total quantity of charge and the time to carry out step a) can vary, for example based on the combination of the current density applied and the anode surface employed, as well as on the amount of gadolinium to dissociate from the GBCA, etc. Accordingly, the optimal conditions of quantity of charge and time to carry out step a) can be selected according to conventional and standard knowledge in the art, as well as by using ordinary analytical means to detect the completion of the reaction, such as ICP method mentioned below. By way of example, a time suitable to carry out step a) can be of 1 hour or more, preferably of 2 hours or more, more preferably of 3 hours or more, even more preferably of 4 hours or more, and most preferably of 6 hours or more.

[0038] According to an embodiment, during step a), one or more steps of inversion of polarity can be carried out. As used herein, "inversion of polarity" refers to the process of reversing the direction of the electric current in the electrochemical cell, whereby the roles of the anode and of the cathode are reversed. This embodiment can be advantageous, particularly when the method of the invention is carried out at industrial scale, as it might help clean the electrodes and prevent or reduce fouling. According to this embodiment, it might be advantageous that the anode and cathode are based on the same material, e.g. the ones mentioned above.

[0039] According to an embodiment, step a) is carried out by insufflating oxygen (O2) into the solution, for example a flow of oxygen of 10 to 100 mL / min, preferably 20 to 50 mL / min. It has been found that this embodiment improves the current efficiency of the electrolysis of step a).

[0040] Step b) provides for precipitating gadolinium ions obtained from the electrolysis of step a), particularly from the dissociation of gadolinium from the GBCA, preferably by means of a counter-anion forming an insoluble or scarcely soluble gadolinium salt in the (aqueous) solution. Accordingly, step b) can be carried out by precipitating the gadolinium ions with a suitable counter-anion. Suitable counter-anions can be selected from the group consisting of phosphate, carbonate, oxalate, hydroxide, and mixtures thereof; preferably, the counteranion is selected from the group consisting of phosphate, carbonate, and mixtures thereof. Step b) is particularly advantageous in that it overcomes or reduces the issue related to the toxicity of gadolinium ions dissolved in a solution; indeed, by precipitating such gadolinium ions, they are subtracted from the solution, thus reducing the toxicity of the solution. Moreover, the precipitation allows to easily separate gadolinium from the solution (step c)): indeed, once precipitated in solid form, gadolinium can be easily recovered from the solution using conventional means, such as by filtration; accordingly, the precipitation allows to recover the critical raw material gadolinium.

[0041] According to an embodiment, step b) is carried out by precipitating the gadolinium ions with a counter-anion that is comprised within the solution and / or is generated by the electrolysis of step a), e.g. the counter-anion mentioned above. According to this embodiment, it has been found that, by carrying out the method of the invention, the precipitation of step b) immediately occurs once the current is applied to the anode, that is when the gadolinium ions are liberated due to step a), and keeps occurring as long as gadolinium ions are obtained (that is, during the electrolysis step a)); indeed, when the current is applied to the anode, the electrolysed solution starts clouding, indicating the precipitation of gadolinium ions as gadolinium in solid form. This provides several advantages: first, the issue of the toxicity of gadolinium ions is readily overcome or reduced, because most of gadolinium ions are immediately subtracted from the solution. Second, it improves the efficiency of the method of the invention, because it immediately lowers the concentration of gadolinium ions within the solution, thus further driving forward the dissociation occurring due the electrolysis reaction of step a). Moreover, it has been found that, in certain conditions, carbonate ions ( / .e. the counter-anion forming an insoluble or scarcely soluble gadolinium salt in the aqueous solution) can advantageously be comprised within the solution as a consequence of the electrochemical oxidation of GBCAs (e.g. when the oxidation of GBCAs provides carbonate ions as product or by-product) and / or due to the equilibrium within the solution and air; this is showed e.g. in Examples 7 to 11.

[0042] According to an embodiment, within the solution comprising a GBCA, the counter-anion, such as the one mentioned above, is at least in a stoichiometric amount with respect to the GBCA; preferably, the counter-anion is in a molar excess with respect to the GBCA. By way of example, the counter-anion is in an amount of 1 mol / mol or higher, preferably of 1.5 mol / mol or higher, more preferably of 2 mol / mol or higher, even more preferably of 3 mol / mol or higher, and even more preferably of 5 mol / mol or higher, with respect to the GBCA. This allows to efficiently and effectively precipitate the gadolinium ions that are liberated from the electrolysis step a).

[0043] According to an embodiment, the pH of the solution during step b) is maintained at 4.5 or higher, preferably at 5 or higher, more preferably at 5.5 or higher, even more preferably at 6 or higher, most preferably at 6.5 or higher; and / or at 11 or lower, preferably at 8 or lower, more preferably at 7.5 or lower. According to an embodiment, the pH of the solution during step a) is maintained at 4.5 to 11, preferably at 5 to 11, more preferably at 5.5 to 11, and even more preferably at 6 to 11, such as at 6 to 9, or at 6 to 7.5. According to a preferred embodiment, particularly when steps a) and b) are carried out simultaneously, the pH of the solution during step b) is the same as the pH of the solution during step a).

[0044] Step b) can be advantageously carried out without controlling the temperature of the reaction. According to a preferred embodiment, particularly when steps a) and b) are carried out simultaneously, the temperature of the solution during step b) is the same as the temperature of the solution during step a).

[0045] According to an embodiment, during step a) and / or b), the solution is kept under stirring, for example by conventional means, such as magnetic stirring.

[0046] Step c) provides for separating the gadolinium in solid form obtained in the previous step b) from the solution. This can be carried out by conventional means, for example via filtration or centrifugation. Thus, according to an embodiment, step c) is carried out by filtering out the gadolinium in solid form from the solution. This step allows to effectively recover the critical raw material gadolinium from waste solutions containing it; gadolinium recovered in this way can be re-used e.g. for manufacturing GBCAs.

[0047] Experimental section

[0048] Material and methods

[0049] Reactants, materials, and / or solvents employed in the following Examples are known and readily available (e.g. commercially available); if not, they may be prepared according to methods known in literature or as set out in the Examples.

[0050] Artificial urine used in the following Examples was obtained according to Sarigul, N. et al., A New Artificial Urine Protocol to Better Imitate Human Urine, Sci Rep 9, 20159 (2019), was at pH 6.5, and comprised the concentration of chloride, oxalate, and phosphate ions set out in Table 1 :

[0051] Table 1

[0052] The total organic carbon (TOC) content was determined using TOC-L CPH by Shimadzu Italia S.r.l., which measures the total carbon and inorganic carbon present in solution through high temperature combustion catalytic oxidation method. Samples were diluted 1: 10 or 1 :20 (depending on the concentration range) in 40 mL test tubes and analyzed. Potassium hydrogen phthalate, sodium hydrogen carbonate and sodium carbonate were used for calibration curves.

[0053] The chemical oxygen demand (COD) of solutions was analyzed using COD Cell Test (Photometric, 500-10000 mg / L, Spectroquant). 1 mL of reaction solution diluted 1:2 was transferred in the specific cuvette and heated at 148 °C for 2 hours in the thermoreactor (Spectroquant®), where the sample was oxidized with potassium dichromate, and then the concentration of Cr3+was determined photometrically (Spectroquant®).

[0054] ICP-OES Optima 2100 DV, Perkin Elmer was used to analyze the solutions and the filtered powders for the quantification of Gd, P, Na, K and Ca with a calibration curve for the elements, monitoring the areas of the emission peak of Gd (A = 376.839 nm), P (A = 214.913 nm), Na (A = 589.592 nm), K (A = 766.490 nm) and Ca (A = 315.889 nm). Rh was used as internal standard (A = 343.389 nm). For the analyses, the solutions were diluted 1 :400, 1:80 or 1 :40 (depending on the concentration range) in nitric acid 2%. For the solids, 10 mg of powder were dissolved 20 mL in nitric acid and then diluted 1:50 for the determination of Gd and P, while 1 : 10 for the determination of Na, K and Ca.

[0055] Example 1 - Recovery of gadolinium from artificial urine comprising gadoteridol with electrodes based on Pt

[0056] 1280 mg of gadoteridol (Bracco Imaging S.p.A., 1.961 mmol calculated by ICP) were added to 100 mL of artificial urine solution in an open reactor with two electrodes based on platinum (in particular, electrodes made of platinum foil) (geometric area: 6 cm2). 1.2 A (0.2 A / cm2) was applied to the anode; the solution immediately became cloudy, indicating the formation of a powder. After 3 hours, the resulting white powder was filtered on buchner and dried in oven at 150 °C, and 570 mg were collected. XRD analysis of the white powder after its calcination at 650 °C for 2 hours showed that the white powder was gadolinium phosphate (GdPC ). Based on the purity of the white powder and on the amount of water comprised therein, about 97% of gadolinium was recovered (calculated with measurements of gadolinium content by ICP). 64% of current efficiency was calculated using the COD values of the initial and final solutions, considering the difference of initial and final volumes, due to water evaporation over time due to the electric resistance.

[0057] Example 2 - Recovery of gadolinium from artificial urine comprising gadoteridol with electrodes based on Pt

[0058] 1280 mg of gadoteridol (Bracco Imaging S.p.A., 1.961 mmol calculated by ICP) were added to 100 mL of artificial urine solution in an open reactor with two electrodes based on platinum (geometric area: 5 cm2). 1 A (0.2 A / cm2) was applied to the anode; the solution immediately became cloudy, indicating the formation of a powder. After 3 hours, the resulting white powder was filtered on buchner and dried in oven at 150 °C, and 560 mg were collected. IR analysis of the white powder confirmed that the white powder was gadolinium phosphate (GdPC ). Based on the purity of the white powder and on the amount of water comprised therein, about 99% of gadolinium was recovered (calculated with measurements of gadolinium content by ICP). The current efficiency was 73%. This Example 2, carried out with almost the same conditions of Example 1, demonstrates the reproducibility of the method of the invention.

[0059] The method was carried out in the same conditions for 6 hours, obtaining 583 mg of white powder. Based on the purity of the white powder and on the amount of water comprised therein, about 97% gadolinium (yield by ICP) was recovered. The current efficiency decreased to 49%. TOC after 6 hours was lower compared to TOC after 3 hours, meaning that the method of the invention advantageously was able to oxidise further compounds comprised within the artificial urine.

[0060] Example 3 - Recovery of gadolinium from artificial urine comprising gadoteridol with electrodes based on Pt and with inversion of polarity

[0061] The reaction was carried out in the same conditions of Example 2 (0.2 A / cm2applied on Pt anode) for 3 hours, with inversion of polarity after 1.5 hours (the anode and cathodes were inverted). 550 mg of white powder were collected. IR analysis of the white powder confirmed that the white powder was gadolinium phosphate (GdPC ). Based on the purity of the white powder and on the amount of water comprised therein, 99% of gadolinium was recovered. The current efficiency was 68%.

[0062] Example 4 - Recovery of gadolinium from artificial urine comprising gadoteridol with anode based on Pt, cathode based on Pt, and with lower current density

[0063] 1280 mg of gadoteridol (Bracco Imaging S.p.A., 1.961 mmol calculated by ICP) were added to 100 mL of artificial urine solution, in an open reactor with an anode based on platinum (geometric area: 5 cm2), and cathode based on platinum (in particular, a platinum foil). 0.4 A (0.08 A / cm2) was applied to the anode; the solution immediately became cloudy, indicating the formation of a powder. After 3 hours, the resulting white powder was filtered on buchner and dried in oven at 150°C, and 340 mg were collected. IR analysis of the white powder confirmed that the white powder was gadolinium phosphate (GdPCk). Based on the purity of the white powder and on the amount of water comprised therein, 52% of gadolinium was recovered. The current efficiency was 82%.

[0064] The method was carried out in the same conditions for 6 hours, obtaining 540 mg of solid powder. Based on the purity of the white powder and on the amount of water comprised therein, 82% of gadolinium was recovered, and 74% of current efficiency.

[0065] Example 5 - Recovery of gadolinium from artificial urine comprising gadoteridol with anode based on Pt, with lower current density, and with O2 insufflation

[0066] 1280 mg of gadoteridol (Bracco Imaging S.p.A., 1.961 mmol calculated by ICP) were added to 100 mL of artificial urine solution, in a reactor with an anode based on platinum (geometric area: 5 cm2), and a Pt foil cathode. 0.4 A (0.08 A / cm2) was applied to the anode; the solution immediately became cloudy, indicating the formation of a powder. O2 was insufflated in solution during the electrolysis. After 3 hours, the resulting white solid powder was filtered on buchner and dried in oven at 150°C; 347 mg were collected. IR analysis of the white powder confirmed that the white powder was gadolinium phosphate (GdPC ). Based on the purity of the white powder and on the amount of water comprised therein, 59% of gadolinium was recovered. The current efficiency raised to 96%.

[0067] The method was carried out in the same conditions for 6 hours, obtaining 527 mg of solid powder. Based on the purity of the white powder and on the amount of water comprised therein, 92% of gadolinium was recovered, with 71% of current efficiency.

[0068] Example 6 - Recovery of gadolinium from artificial urine comprising gadoteridol with anode based on Pt, stainless-steel grid cathode, and with lower current density

[0069] 1280 mg of gadoteridol (Bracco Imaging S.p.A., 1.961 mmol calculated by ICP) were added to 100 mL of artificial urine solution, in a reactor with an anode based on platinum (geometric area: 5 cm2), and a stainless-steel grid cathode. 0.4 A (0.08 A / cm2) was applied to the anode for 6 hours; the solution immediately became cloudy, indicating the formation of a powder. The resulting white solid powder was filtered on buchner and dried in oven at 150°C, and 490 mg were collected. IR analysis of the white powder confirmed that the white powder was gadolinium phosphate (GdPC ). Based on the purity of the white powder and on the amount of water comprised therein, 86 % of gadolinium was recovered. The current efficiency was 75%.

[0070] Example 7 - Recovery of gadolinium from NaCI aqueous solutions comprising gadoteridol, with anode based on iridium and ruthenium oxides, and cathode based on Pt

[0071] An anode based on iridium and ruthenium oxides (geometric area: 6 cm2) was prepared as follows: 1 mL of 0.1 M IrCh and 0.1 M RuCh suspension in ethanol (total concentration: 0.2 M) was prepared. The suspension was deposited onto a 6 cm2titanium sheet, which had been pre-treated with oxalic acid, ensuring approximately 1 mg of material per cm2. The coated sheet was dried in oven and then calcined at 500°C for 15 minutes.

[0072] In a reactor with the anode prepared as above, and a cathode based on platinum, 640 mg of gadoteridol (Bracco Imaging S.p.A., equal to 1.04 mmol of gadoteridol) was added to 50 mL of ultrapure water together with NaCI (concentration of NaCI: 3 g / L). A current density of 0.067 A / cm2was applied to the anode; the solution immediately became cloudy, indicating the formation of a powder. After 3 hours, the white powder was filtered with centrifuge and dried in oven at 150 °C. IR analysis of the white powder confirmed that the white powder was gadolinium carbonate (Gd2(COs)3). Based on the purity of the white powder and on the amount of water comprised therein, 63% of gadolinium was recovered. The current efficiency was 85%. Example 8 - Recovery of gadolinium from NaCI aqueous solutions comprising gadoteridol, with anode based on iridium and ruthenium oxides, and cathode based on Pt

[0073] In a reactor with an anode based on iridium and ruthenium oxides (geometric area: 7 cm2) and a Pt cathode, 2 mL of ProHance™ 0.5 M (Bracco Imaging S.p.A., equal to 1 mmol of gadoteridol) was added to 50 mL of ultrapure water together with 150 mg of NaCI. 0.2 A (0.03 A / cm2) was applied to the anode; the solution immediately became cloudy, indicating the formation of a powder. After 12 hours, the white powder was filtered with centrifuge and dried in oven at 150 °C. 216 mg of white powder were collected. XRD analysis of the white powder showed that the white powder was gadolinium carbonate (Gd2(COs)3). Based on the purity of the white powder and on the amount of water comprised therein, 75% of gadolinium was recovered. The current efficiency was 52%.

[0074] Example 9 - Recovery of gadolinium from NaCI aqueous solutions comprising gadobenate, with anode based on iridium and ruthenium oxides, and cathode based on Pt

[0075] The present Example was carried out in the same conditions of Example 7, however instead of ProHance™, 2 mL of MultiHance™ 0.5 M (Bracco Imaging S.p.A., equal to 1 mmol of gadobenate) was added to the 50 mL of ultrapure water together with 150 mg of NaCI. 203 mg of white powder were collected. Based on the purity of the white powder and on the amount of water comprised therein, 75% of gadolinium was recovered. The current efficiency was 78%.

[0076] Example 10 - Recovery of gadolinium from NaCI aqueous solutions comprising gadoterate, with anode based on iridium and ruthenium oxides, and cathode based on Pt

[0077] The present Example was carried out in the same conditions of Example 7, however instead of ProHance™, 2 mL of Dotarem™ 0.5 M (Guerbet, equal to 1 mmol of gadoterate) was added to the 50 mL of ultrapure water together with 150 mg of NaCI. 194 mg of white powder were collected. Based on the purity of the white powder and on the amount of water comprised therein, 71% of gadolinium was recovered. The current efficiency was 50%.

[0078] Example 11 - Recovery of gadolinium from NaCI aqueous solutions comprising gadobutrol, with anode based on iridium and ruthenium oxides, and cathode based on Pt

[0079] The present Example was carried out in the same conditions of Example 7, however instead of ProHance™, 1 mL of Gadovist™ 1 M (Bayer, equal to 1 mmol of gadobutrol) was added to the 50 mL of ultrapure water together with 150 mg of NaCI. 205 mg of white powder were collected. Based on the purity of the white powder and on the amount of water comprised therein, 72% gadolinium was recovered. The current efficiency was 51%.

[0080] Example 12 - Recovery of gadolinium from wastewater solution comprising gadoteridol, with electrodes based on Pt

[0081] 100 mL of an aqueous solution at pH 11 sampled from the plant for manufacturing gadoteridol (wastewater) comprising 0.0018 M of gadolinium (calculated by ICP) was loaded into a reactor with electrodes based on platinum (geometric area: 6 cm2). 300 mg of NaCI were added to the aqueous solution to achieve a NaCI concentration of 3 g / L. A current density of 0.33 A / cm2was applied to the anode; the solution immediately became cloudy, indicating the formation of a powder. After 3 hours, the white powder was filtered with centrifuge and dried in oven at 150 °C. XRD analysis of the white powder showed an amorphous precipitate. Based on the purity of the white powder and on the amount of water comprised therein, 62% of gadolinium was recovered.

Claims

CLAIMS1. A method of separating gadolinium from a solution comprising at least one gadolinium-based contrast agent comprising the following steps: a) carrying out an electrolysis of the solution to dissociate gadolinium from the gadolinium-based contrast agent, thereby obtaining gadolinium ions; b) precipitating the gadolinium ions obtained from step a) to obtain gadolinium in solid form; and c) separating the gadolinium in solid form from the solution.

2. The method according to claim 1, wherein step b) is carried out during step a).

3. The method according to claim 1 or 2, wherein the gadolinium-based contrast agent is selected from the group consisting of: gadoterate, gadobutrol, gadopentetate, gadobenate, gadodiamide, gadoversetamide, gadoteridol, gadofosveset, gadoxetate, gadopiclenol, and gadoquatrane.

4. The method according to claim 3, wherein the gadolinium-based contrast agent is selected from the group consisting of: gadoterate, gadobutrol, gadobenate, gadoteridol, gadopiclenol, and gadoquatrane.

5. The method according to any one of claims 1 to 4, wherein the solution comprises chloride ions.

6. The method according to claim 5, wherein the amount of chloride ions comprised in the solution is 0.01 mol or higher with respect to 1 mol of gadolinium- based contrast agent.

7. The method according to claim 6, wherein the amount of chloride ions comprised in the solution is 0.1 mol or higher with respect to 1 mol of gadolinium- based contrast agent.

8. The method according to claim 7, wherein the amount of chloride ions comprised in the solution is 1 mol or higher with respect to 1 mol of gadolinium-based contrast agent.

9. The method according to claim 8 wherein the amount of chloride ions comprised in the solution is 2 mol or higher with respect to 1 mol of gadolinium-based contrast agent; and10. The method according to claim 9 wherein the amount of chloride ions comprised in the solution is 2.5 mol or higher with respect to 1 mol of gadolinium- based contrast agent.

11. The method according to any one of claims 1 to 10, wherein the solution is an aqueous solution.

12. The method according to claim 11, wherein the solution is wastewater or urine.

13. The method according to any one of claims 1 to 12, wherein the concentration of the gadolinium-based contrast agent comprised in the solution is of 0.0001 M or higher.

14. The method according to claim 13, wherein the concentration of the gadolinium-based contrast agent comprised in the solution is of 0.001 M or higher.

15. The method according to claim 14, wherein the concentration of the gadolinium-based contrast agent comprised in the solution is of 0.01 M or higher.

16. The method according to claim 15, wherein the concentration of the gadolinium-based contrast agent comprised in the solution is of 0.02 M or higher.

17. The method according to any one of claims 1 to 16, wherein the concentration of the gadolinium-based contrast agent comprised in the solution is of 2 M or lower.

18. The method according to claim 17, wherein the concentration of the gadolinium-based contrast agent comprised in the solution is of 1 M or lower.

19. The method according to claim 18, wherein the concentration of the gadolinium-based contrast agent comprised in the solution is of 0.1 M or lower.

20. The method according to any one of claims 1 to 19, wherein the pH of the solution during step a) and / or b) is maintained at 4.5 or higher.

21. The method according to claim 20, wherein the pH of the solution during step a) and / or b) is maintained at 5 or higher.

22. The method according to claim 21, wherein the pH of the solution during step a) and / or b) is maintained at 5.5 or higher23. The method according to claim 22, wherein the pH of the solution during step a) and / or b) is maintained at 6 or higher.

24. The method according to claim 23, wherein the pH of the solution during step a) and / or b) is maintained at 6.5 or higher.

25. The method according to any one of claims 1 to 24, wherein the pH of the solution during step a) and / or b) is maintained at 11 or lower.

26. The method according to claim 25, wherein the pH of the solution during step a) and / or b) is maintained at 8 or lower.

27. The method according to claim 26, wherein the pH of the solution during step a) and / or b) is maintained at 7.5 or lower.

28. The method according to any one of claims 1 to 27, wherein step a) is carried out using an anode based on an element having an atomic number from 5 to 82, oxides thereof, and mixtures thereof.

29. The method according to claim 28, wherein step a) is carried out using an anode based on an element comprised within period 3 and period 5 of the periodic table, boron, lead, tantalum, platinum, iridium, oxides thereof, and mixtures thereof.

30. The method according to claim 29, wherein the anode is based on a material selected from the group consisting of platinum, titanium, iridium, ruthenium, tin, tantalum, antimony, lead, boron, rhodium, oxides thereof, and mixtures thereof.

31. The method according to any one of claims 1 to 30, wherein step a) is carried out using a cathode based on an element having an atomic number from 5 to 82, oxides thereof, and mixtures thereof.

32. The method according to claim 31, wherein step a) is carried out using a cathode based on an element comprised within period 3 and period 5 of the periodic table, boron, lead, tantalum, platinum, iridium, oxides thereof, and mixtures thereof.

33. The method according to claim 32, wherein the cathode is based on a material selected from the group consisting of platinum, titanium, iridium, ruthenium, tin, tantalum, antimony, lead, boron, rhodium, iron, nickel, oxides thereof, and mixtures thereof.

34. The method according to any one of claims 1 to 33, wherein step b) is carried out by precipitating the gadolinium ions with a counter-anion that is comprised within the solution and / or is generated by the electrolysis of step a).

35. The method according to claim 34, wherein the counter-anion is selected from the group consisting of phosphate, carbonate, oxalate, hydroxide, and mixtures thereof.

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