Radioactive isotope purification apparatus and radioactive isotope purification method

Abstract

To provide a radioisotope refining device and a radioisotope refining method capable of refining a radioisotope limited in impurities.SOLUTION: A holding / separating unit 3 holds a radioisotope by a first resin material. Thus, the radioisotope is separated from impurities included in a radioisotope-containing solution. Then, a fluid feed unit 1 feeds an extraction solution for extracting the held radioisotope to the holding / separating unit 3. Thus, the radioisotope is separated from the holding / separating unit 3 to be recoverable with the impurities removed. The holding / separating unit 3 holds and separates the radioisotope by a first resin material containing a compound having a phosphorus-oxygen bond. As the first resin material contains the compound having the phosphorus-oxygen bond, the radioisotope can be extracted with a limited extraction solution amount by reducing the impurities mixed in the radioisotope.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a radioisotope purification apparatus and a radioisotope purification method.

Background Art

[0002] For example, a radioisotope-labeled compound used in a PET examination (positron emission tomography examination) or the like in a hospital or the like is used. Ga-68 is adopted as the radioisotope used in such a labeled compound (Patent Document 1).

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] Ga-68 is produced, for example, by irradiating a solid target with a particle beam in a cyclotron to cause a nuclear reaction of

[0006] , , , Zn(p,n) 68 Ga. Therefore, in a solution containing Ga-68 obtained by dissolving this solid target, there is a possibility that target materials (Zn-68) and metal ions from the environment (typically Fe ions) may be mixed in. Since the amount of the produced Ga-68 is very small, there is a concern that the mixing of other metal ions may have an adverse effect on subsequent processes.

[0005] Therefore, an object of the present invention is to provide a radioisotope purification apparatus and a radioisotope purification method capable of purifying a radioisotope with few impurities.

Means for Solving the Problems

[0006] A radioactive isotope purification apparatus according to one aspect of the present invention is a radioactive isotope purification apparatus for purifying Ga-68 as a radioactive isotope, comprising a holding and releasing section for holding and releasing radioactive isotopes using a first resin material containing a compound having a phosphorus-oxygen bond, a radioactive isotope-containing solution containing radioactive isotopes being supplied to the holding and releasing section, and an extraction solution for extracting the held radioactive isotopes being supplied to the holding and releasing section.

[0007] The radioactive isotope purification apparatus supplies a radioactive isotope-containing solution containing radioactive isotopes to the holding and detachment section. The holding and detachment section then holds the radioactive isotopes using a first resin material. This separates the radioactive isotopes from impurities in the radioactive isotope-containing solution. Next, the radioactive isotope purification apparatus supplies an extraction solution to the holding and detachment section to extract the held radioactive isotopes. This allows the radioactive isotopes, free from impurities, to detach from the holding and detachment section and be recovered. Here, the holding and detachment section holds and detaches the radioactive isotopes using a first resin material containing a compound with a phosphorus-oxygen bond. The inclusion of a compound with a phosphorus-oxygen bond in the first resin material reduces impurities mixed with the radioactive isotopes, making it possible to extract the radioactive isotopes with a smaller amount of extraction solution. Therefore, radioactive isotopes with fewer impurities can be purified.

[0008] The first resin material has a compound of the form "(R1O)(R2O)(R3O)PO", where R1, R2, and R3 may be a linear alkyl group having 2 to 8 carbon atoms, a branched alkyl group having 3 to 8 carbon atoms, a hydrocarbon group having 3 to 8 carbon atoms with an unsaturated bond, or an aromatic group. In this case, it is possible to reduce impurities mixed with the radioactive isotope and extract the radioactive isotope with a small amount of extraction solution.

[0009] The first resin material may contain any of the following compounds: tributyl phosphate (TBP), diamylamylphosphonic acid (DA[AP]), trioctylphosphine oxide (TOPO), bis(2-ethylhexyl) phosphate (HDEHP), 2-ethylhexyl 2-ethylhexylphosphonic acid-2-ethylhexyl (HEH[EHP]), or bis(2,4,4-trimethylpentyl)phosphinic acid (H[DTMPP]). In this case, it is possible to reduce impurities mixed with the radioactive isotope and extract the radioactive isotope with a small amount of extraction solution.

[0010] The first resin material may contain a tributyl phosphate (TBP) compound. In this case, by employing a particularly preferred compound as the retention and release portion, it becomes possible to reduce impurities mixed with the radioactive isotope and extract the radioactive isotope with a smaller amount of extraction solution.

[0011] The radioactive isotope purification apparatus may further include an acidity adjustment unit for adjusting the acidity of the extraction solution containing the radioactive isotope released from the retention and release unit. In this case, the acidity adjustment unit can adjust the acidity of the radioactive isotope to be suitable for the synthesis of Ga-labeled compounds.

[0012] The acid concentration of the radioactive isotope-containing solution may be higher than that of the extraction solution. The acid concentration of the radioactive isotope-containing solution is such that it can retain the radioactive isotope in the first resin material, while the concentration of the extraction solution is such that it can elute the radioactive isotope from the first resin material. As a result, when the radioactive isotope-containing solution is supplied to the first resin material, the radioactive isotope is well retained in the first resin material containing a compound with a phosphorus-oxygen bond, impurities are separated, and then the radioactive isotope retained in the first resin material can be well purified.

[0013] Before supplying the extraction solution to the retention / release section, a washing solution with a higher acid concentration than the extraction solution may be supplied. The acid concentration of the washing solution is such that it can retain radioactive isotopes from the first resin material, and the concentration of the extraction solution is such that it can elute radioactive isotopes from the first resin material. This allows for good retention of radioactive isotopes in the first resin material containing a phosphorus-oxygen bond while removing impurities originating from the radioactive isotope-containing solution, and then effectively purifying the radioactive isotopes retained in the first resin material.

[0014] The radioactive isotope-containing solution and the extraction solution are both hydrochloric acid solutions, and the radioactive isotope-containing solution may have a concentration of 3M to 12M. This ensures that the radioactive isotope is well retained in the first resin material containing a compound with a phosphorus-oxygen bond.

[0015] The radioactive isotope-containing solution and the extraction solution are both hydrochloric acid solutions, and the extraction solution may have a concentration of 0.1 M to 2 M. This allows for effective detachment of the radioactive isotope retained in the first resin material containing a compound having a phosphorus-oxygen bond.

[0016] The first resin material has a volume of 0.1 mL to 2.0 mL and contains a tributyl phosphate compound, and the washing solution is a hydrochloric acid solution with a concentration of 3 to 10 M, and the amount of washing solution may be 10 mL or more. In this case, impurities can be effectively removed from the first resin material.

[0017] The radioactive isotopes contained in the radioactive isotope solution may be produced using an accelerator. In this case, the required amount of radioactive isotope can be obtained at a high yield and when needed.

[0018] The method for purifying a radioisotope according to one aspect of the present invention is a method for purifying Ga-68 as a radioisotope, which retains and releases the radioisotope with a first resin material containing a compound having a phosphorus-oxygen bond, supplies a radioisotope-containing solution containing the radioisotope to the first resin material, and supplies an extraction solution for extracting the radioisotope retained by the first resin material.

[0019] According to this method for purifying a radioisotope, the same operations and effects as those of the above-described radioisotope purification apparatus can be obtained.

Effects of the Invention

[0020] According to the present invention, a radioisotope purification apparatus capable of purifying a radioisotope with few impurities and a method for purifying a radioisotope can be provided.

Brief Description of the Drawings

[0021] [Figure 1] It is a schematic configuration diagram showing a radioisotope purification apparatus according to an embodiment of the present invention. [Figure 2] It is a diagram showing a purification method by a radioisotope purification apparatus. [Figure 3] It is a schematic configuration diagram showing the flow of fluid in a radioisotope purification apparatus in each step. [Figure 4] It is a schematic configuration diagram showing the flow of fluid in a radioisotope purification apparatus in each step. [Figure 5] It is a schematic configuration diagram showing the flow of fluid in a radioisotope purification apparatus in each step. [Figure 6] It is a schematic configuration diagram showing the flow of fluid in a radioisotope purification apparatus in each step. [Figure 7] It is a schematic configuration diagram showing the flow of fluid in a radioisotope purification apparatus in each step. [Figure 8] It is a diagram showing an example of the chemical structure of the compound of the first resin material. [Figure 9] It is a graph showing experimental results. [Figure 10]This is a conceptual diagram of a radiopharmaceutical production system, including a radioactive isotope purification system using an accelerator. [Figure 11] This is a conceptual diagram of a radioactive drug production system using a generator. [Modes for carrying out the invention]

[0022] The following describes a radioactive isotope purification apparatus according to one embodiment of the present invention, with reference to the attached drawings. In the description of the drawings, the same elements are denoted by the same reference numerals, and redundant explanations are omitted.

[0023] Figure 1 is a schematic diagram showing a radioactive isotope purification apparatus 100 according to one embodiment of the present invention. The radioactive isotope purification apparatus 100 is a device for purifying Ga-68 as a radioactive isotope. The radioactive isotope purification apparatus 100 comprises a fluid supply unit 1, a fluid control unit 2, a holding and release unit 3, a waste liquid recovery unit 4, an acidity adjustment unit 6, and a solution recovery unit 7. Note that the radioactive isotope purification apparatus also includes devices that have a radioactive isotope purification function provided in a synthesis apparatus.

[0024] The fluid supply unit 1 supplies fluid to the holding / releasing unit 3 and the acidity adjustment unit 6 via the fluid control unit 2. The fluid supply unit 1 comprises a first supply unit 11, a second supply unit 12, a third supply unit 13, a fourth supply unit 14, and a fifth supply unit 15.

[0025] The first supply unit 11 supplies a radioactive isotope-containing solution containing radioactive isotopes to the holding and releasing unit 3. The first supply unit 11 is composed of a vial containing the radioactive isotope-containing solution. A line L1 for supplying a pressurized gas such as nitrogen is connected to the first supply unit 11. A line L2 for transporting the radioactive isotope-containing solution recovered from the upstream cyclotron (solid target) is connected to the first supply unit 11. A line L3 for supplying the radioactive isotope-containing solution to the fluid control unit 2 is connected to the first supply unit 11. The radioactive isotope-containing solution is an aqueous solution containing an acid, and the acid is selected from, for example, hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, etc.

[0026] The second supply unit 12 supplies the cleaning solution to the holding / releasing unit 3. The second supply unit 12 is composed of a vial containing the cleaning solution. For example, concentrated hydrochloric acid (6M hydrochloric acid) is used as the cleaning solution. A line L4 is connected to the second supply unit 12 to supply the cleaning solution to the fluid control unit 2. The third supply unit 13 supplies the extraction solution to the holding / releasing unit 3. The third supply unit 13 is composed of a vial containing the extraction solution. For example, dilute hydrochloric acid (0.5M hydrochloric acid) is used as the extraction solution. A line L5 is connected to the third supply unit 13 to supply the extraction solution to the fluid control unit 2.

[0027] The fourth supply unit 14 supplies the cleaning solution to the acidity adjustment unit 6. The fourth supply unit 14 consists of a vial containing the cleaning solution. For example, dilute hydrochloric acid (0.5M hydrochloric acid) is used as the cleaning solution. A line L6 that supplies the cleaning solution to the fluid control unit 2 is connected to the fourth supply unit 14. The fifth supply unit 15 supplies the extraction solution to the acidity adjustment unit 6. The fifth supply unit 15 consists of a vial containing the extraction solution. For example, dilute hydrochloric acid (0.1M hydrochloric acid) is used as the extraction solution. A line L7 that supplies the extraction solution to the fluid control unit 2 is connected to the fifth supply unit 15.

[0028] The retention and release section 3 retains and releases radioactive isotopes using a first resin material. The retention and release section 3 is constructed by housing the first resin material in a column. A line L8 from the fluid control unit 2 is connected to the inlet of the retention and release section 3, and a line L9 extending to the fluid control unit 2 is connected to the outlet.

[0029] The holding and releasing section 3 is supplied with a radioactive isotope-containing solution from the first supply section 11 of the fluid supply section 1, and holds the radioactive isotopes contained in the radioactive isotope-containing solution in the first resin material. The holding and releasing section 3 allows impurities contained in the radioactive isotope-containing solution (impurities such as Zn contained in the target material) to pass through the solution and flow to line L9. The holding and releasing section 3 is supplied with a cleaning solution from the second supply section 12 of the fluid supply section 1, and releases any remaining impurities, which are then flowed to line L9 along with the cleaning solution. The impurities that have flowed out of the holding and releasing section 3 are recovered by the waste liquid recovery section 4 via the fluid control section 2.

[0030] Furthermore, the holding and releasing section 3 receives the extraction solution supplied from the third supply section 13 of the fluid supply section 1, releasing the radioactive isotopes it holds and flowing them together with the extraction solution to line L9. The radioactive isotopes released from the holding and releasing section 3 are supplied to the acidity adjustment section 6 via the fluid control section 2.

[0031] The radioactive isotope-containing solution supplied from the first supply unit 11 and the washing solution supplied from the second supply unit 12 have a higher acid concentration than the extraction solution supplied from the third supply unit 13. The radioactive isotope-containing solution and the washing solution have a high acid concentration in order to retain the radioactive isotope in the first resin material. On the other hand, the extraction solution has a relatively low acid concentration in order to release the radioactive isotope from the retention / release unit 3.

[0032] When the radioactive isotope-containing solution, washing solution, and extraction solution are all hydrochloric acid solutions, the radioactive isotope-containing solution and washing solution have concentrations of, for example, 3 to 12 M, preferably 6 to 10 M. A concentration of 3 M or higher ensures that the radioactive isotope is retained in the first resin material containing the phosphorus-oxygen bonded compound. The extraction solution has a concentration of, for example, 0.1 to 2 M, preferably 0.1 to 0.5 M. This allows the radioactive isotope retained in the first resin material containing the phosphorus-oxygen bonded compound to be released.

[0033] The first resin material used in the retaining / detaching part 3 has a volume of 0.1 mL to 2.0 mL, preferably 0.3 mL. The concentration of the cleaning solution used to clean the retaining / detaching part 3 is 3 to 10 M, preferably 6 M. When using 0.3 mL of the first resin material and a 6 M hydrochloric acid cleaning solution, the amount of cleaning solution required is 10 mL or more, preferably 10 mL.

[0034] The acidity adjustment unit 6 adjusts the acidity of the extraction solution containing the radioactive isotope released from the retention / release unit 3. For example, the acidity adjustment unit 6 can be used to adjust the pH of the radioactive isotope solution after purification of the radioactive isotope in this embodiment so that it has a hydrogen ion concentration (pH) suitable for a reaction solution for drug synthesis. The acidity adjustment unit 6 is constructed by housing a second resin in a column. A line L11 from the fluid control unit 2 is connected to the inlet of the acidity adjustment unit 6, and a line L12 extending to the fluid control unit 2 is connected to the outlet.

[0035] The acidity adjustment unit 6 receives an extraction solution containing radioactive isotopes supplied from the retention / release unit 3, thereby retaining the radioactive isotopes contained in the extraction solution in the second resin material. The acidity adjustment unit 6 allows impurities contained in the extraction solution to pass through together with the extraction solution and flows to line L12. The acidity adjustment unit 6 receives a cleaning solution supplied from the fourth supply unit 14 of the fluid supply unit 1, thereby releasing any remaining impurities, which are then flowed together with the cleaning solution to line L12. The impurities that have flowed out of the acidity adjustment unit 6 are recovered by the waste liquid recovery unit 4 via the fluid control unit 2.

[0036] Furthermore, the acidity adjustment unit 6 receives the extraction solution supplied from the fifth supply unit 15 of the fluid supply unit 1, thereby flowing the target radioactive isotope Ga-68 into line L12 as a Ga-68 hydrochloric acid solution with an acidity suitable for the labeling reaction. The solution of the radioactive isotope eluted from the acidity adjustment unit 6 is supplied to the solution recovery unit 7 via the fluid control unit 2.

[0037] The waste liquid recovery unit 4 recovers waste liquid from the holding and releasing unit 3 and waste liquid from the acidity adjustment unit 6. The waste liquid recovery unit 4 is composed of a vial that contains the waste liquid. The waste liquid recovery unit 4 is connected to a line L13 that extends from the fluid control unit 2 and is supplied with waste water from the holding and releasing unit 3, and to a line L14 that is supplied with waste water from the acidity adjustment unit 6. A line L16 that reduces the pressure in the waste liquid recovery unit 4 is also connected to it.

[0038] The solution recovery unit 7 recovers the radioactive isotope solution from the acidity adjustment unit 6. The solution recovery unit 7 consists of a vial that contains the solution. A line L17 extending from the fluid control unit 2 is connected to the solution recovery unit 7, supplying the solution from the acidity adjustment unit 6. A line L18 for reducing the pressure in the waste liquid recovery unit 4 is also connected.

[0039] The fluid control unit 2 is a device for controlling the flow of each fluid in the radioactive isotope purification apparatus 100. The fluid control unit 2 is equipped with multiple valves and multiple lines, and controls the flow of fluid in each line by controlling the multiple valves.

[0040] The fluid control unit 2 has a line L3 from the first supply unit 11, a line L8 connected to the holding / releasing unit 3, and a line L20 connected to it. Line L20 is connected to valves VP3, VP1, VP33, and VP34 in order from the line L3 side. From line L20, lines L21 and L22 extend from between valves VP1 and VP33. Line L21 is connected to valves VP17 and VP18. Line L22 is connected to valves VP20, VP21, and VP24 and merges with line L21.

[0041] Line L23 is connected to line L4 from the second supply unit 12, to valve VP4, and to the space between valves VP3 and VP1 of line L20. Line L24 is connected to line L5 from the third supply unit 13, to valves VP5 and VP2, and merges with line L21. Line L26 is connected to line L6 from the fourth supply unit 14, to valve VP6, and to the space between valves VP5 and VP2 of line L24. Line L27 is connected to the external line L10, to valves VP8 and VP19, and to the space between valve VP18 of line L21 and the junction of line L22. Line L28 is connected to line L7 from the fifth supply unit 15, to valve VP7, and to the space between valves VP8 and VP19 of line L27.

[0042] Line L31 is connected between valves VP20 and VP21 of line L22, connected to valves VP22 and VP36, and connected to line L9 from the holding / releasing section 3. Line L32 is connected between valves VP22 and VP36 of line L31, connected to valve VP35, and connected to line L13 to the waste liquid recovery section 4. Line L33 is connected between valves VP21 and VP24 of line L22, connected to valves VP23 and VP39, and connected to line L11 to the acidity adjustment section 6.

[0043] Line L36 is connected to line L12 from the acidity adjustment unit 6, then to valves VP41 and VP40, and then to line L14 leading to the waste liquid recovery unit 4. Line L37 is connected between valves VP41 and VP40 of line L36, then to valves VP30, VP28, VP31, and VP42, and then to line L17 leading to the solution recovery unit 7.

[0044] Referring to Figure 2, the method for purifying radioactive isotopes using the radioactive isotope purification apparatus 100 will be explained. As shown in Figure 2, first, the holding / detaching section 3 is filled with a radioactive isotope-containing solution (step S10). In this case, as shown in Figure 3, the first supply section 11 supplies the radioactive isotope-containing solution to the holding / detaching section 3 via lines L3, L20, and L8 (flow F1). The radioactive isotopes in the radioactive isotope solution are held in the first resin material of the holding / detaching section 3. The solution containing impurities passes through the holding / detaching section 3 and is recovered to the waste liquid recovery section 4 via lines L9, L31, L32, and L13 (flow F2). Here, nitrogen is pumped into the first supply section 11 and the waste liquid recovery section 4 is depressurized to allow the radioactive isotope-containing solution and waste liquid to flow.

[0045] Next, the retaining and releasing section 3 is cleaned with a cleaning solution (step S20). In this case, as shown in Figure 4, the second supply unit 12 supplies the cleaning solution to the retaining and releasing section 3 via lines L4, L23, L20, and L8 (flow F3). The cleaning solution collects impurities held in the first resin material of the retaining and releasing section 3 and is collected in the waste liquid recovery unit 4 via lines L9, L31, L32, and L13 (flow F4). Here, the cleaning solution and waste liquid are discharged by reducing the pressure in the waste liquid recovery unit 4.

[0046] Next, the extraction solution is flowed to the holding / releasing section 3 to release and extract the radioactive isotopes (step S30), and simultaneously filled into the acidity adjustment section 6 (step S40). In this case, as shown in Figure 5, the third supply section 13 supplies the extraction solution to the holding / releasing section 3 via lines L5, L24, L21, L20, and L8 (flow F5). The extraction solution extracts the radioactive isotopes held in the first resin of the holding / releasing section 3 and is supplied to the acidity adjustment section 6 via lines L9, L31, L22, L33, and L11 (flow F6). The radioactive isotopes are held in the acidity adjustment section 6, and impurities are recovered to the waste liquid recovery section 4 via lines L12, L36, and L14 (flow F7). Here, the waste liquid recovery section 4 is depressurized to allow the extraction solution and waste liquid to flow.

[0047] Next, the acidity adjustment unit 6 is cleaned with the cleaning solution (step S50). In this case, as shown in Figure 6, the fourth supply unit 14 supplies the cleaning solution to the acidity adjustment unit 6 via lines L6, L26, L24, L21, L20, L22, L33, and L11 (flow F8). The cleaning solution collects impurities held in the second resin of the acidity adjustment unit 6 and is collected in the waste liquid recovery unit 4 via lines L12, L36, and L14 (flow F9). Here, the cleaning solution and waste liquid are discharged by reducing the pressure in the waste liquid recovery unit 4.

[0048] Next, the extraction solution is flowed to the acidity adjustment unit 6 to adjust the acidity and extract the radioactive isotope (step S60). In this case, as shown in Figure 7, the fifth supply unit 15 supplies the extraction solution to the acidity adjustment unit 6 via lines L7, L28, L27, L21, L22, L33, and L11 (flow F10). The radioactive isotope held in the second resin of the acidity adjustment unit 6 is recovered in the solution recovery unit 7 via lines L12, L36, L37, and L17 (flow F11). Here, the extraction solution is flowed by reducing the pressure in the solution recovery unit 7.

[0049] Next, the first resin material will be described. The first resin material contains a compound having a phosphorus-oxygen bond. The first resin material is obtained by impregnating an inert support with such a compound. The compound may be a compound in which R1, R2, and R3 are any of the following groups when represented as "(R1O)(R2O)(R3O)PO". (i) A linear alkyl group having 2 to 8 carbon atoms may be used, more preferably an ethyl group (a linear alkyl group having 2 carbon atoms), a propyl group (a linear alkyl group having 3 carbon atoms), a pentyl group (a linear alkyl group having 5 carbon atoms), a hexyl group (a linear alkyl group having 6 carbon atoms), or an octyl group (a linear alkyl group having 8 carbon atoms). (ii) It may be a branched alkyl group having 3 to 8 carbon atoms, and more preferably an isopropyl group (a branched alkyl group having 3 carbon atoms) or an isobutyl group (a branched alkyl group having 4 carbon atoms). (iV) A hydrocarbon group having 3 to 8 carbon atoms and having an unsaturated bond may be used. (V) may be an aromatic group, more preferably a phenyl group or a tolyl group.

[0050] Furthermore, the first resin material containing a compound having a phosphorus-oxygen bond may include a compound of tributyl phosphate (TBP) having the chemical structure shown in Figure 8(a). The first resin material may also contain a compound of diamylamylphosphonic acid (DA[AP]) having the chemical structure shown in Figure 8(b). The first resin material may also contain a compound of trioctylphosphine oxide (TOPO) having the chemical structure shown in Figure 8(c). The first resin material may also contain a compound of bis(2-ethylhexyl) phosphate (HDEHP) having the chemical structure shown in Figure 8(d). The first resin material may also contain a compound of 2-ethylhexylphosphonic acid-2-ethylhexyl (HEH[EHP]) having the chemical structure shown in Figure 8(e). The first resin material may also contain a compound of bis(2,4,4-trimethylpentyl)phosphinic acid (H[DTMPP]) having the chemical structure shown in Figure 8(f). In Figure 8, R represents a butyl group.

[0051] Of the compounds mentioned above, it is preferable to use one that includes the tributyl phosphate (TBP) compound shown in Figure 8(a). When tributyl phosphate is represented as "(R1O)(R2O)(R3O)PO", R1, R2, and R3 are "CH3CH2CH2CH2-".

[0052] As a second resin material, trioctylphosphine oxide (TOPO) may be used. In many resins, Ga-68 is not retained in 1-2M hydrochloric acid, but trioctylphosphine oxide (TOPO) has the characteristic of being sufficiently retained in the resin even at hydrochloric acid concentrations of 1-2M.

[0053] Next, the operation and effects of the radioactive isotope purification apparatus 100 according to this embodiment will be described.

[0054] The radioactive isotope purification apparatus 100 supplies a radioactive isotope-containing solution containing radioactive isotopes to the holding and releasing section 3. The holding and releasing section 3 then holds the radioactive isotopes using a first resin material. This separates the radioactive isotopes from impurities in the radioactive isotope-containing solution. Next, the radioactive isotope purification apparatus 100 supplies an extraction solution to the holding and releasing section 3 to extract the held radioactive isotopes. This allows the radioactive isotopes, free from impurities, to be released from the holding and releasing section 3 and recovered. Here, the holding and releasing section 3 uses a first resin material containing a compound with a phosphorus-oxygen bond to hold and release the radioactive isotopes. The inclusion of a compound with a phosphorus-oxygen bond in the first resin material reduces impurities mixed with the radioactive isotopes, making it possible to extract the radioactive isotopes with a smaller amount of extraction solution. Therefore, radioactive isotopes with fewer impurities can be purified.

[0055] The first resin material has a compound of the form "(R1O)(R2O)(R3O)PO", where R1, R2, and R3 may be a linear alkyl group having 2 to 8 carbon atoms, a branched alkyl group having 3 to 8 carbon atoms, a hydrocarbon group having 4 to 8 carbon atoms with an unsaturated bond, or an aromatic group. In this case, it is possible to reduce impurities mixed with the radioactive isotope and extract the radioactive isotope with a small amount of extraction solution.

[0056] The first resin material may contain any of the following compounds: tributyl phosphate (TBP), diamylamylphosphonic acid (DA[AP]), trioctylphosphine oxide (TOPO), bis(2-ethylhexyl) phosphate (HDEHP), 2-ethylhexyl 2-ethylhexylphosphonic acid-2-ethylhexyl (HEH[EHP]), or bis(2,4,4-trimethylpentyl)phosphinic acid (H[DTMPP]). In this case, it is possible to reduce impurities mixed with the radioactive isotope and extract the radioactive isotope with a small amount of extraction solution.

[0057] The first resin material may contain a tributyl phosphate (TBP) compound. In this case, by employing a particularly preferred compound as the retention / release portion 3, it is possible to reduce impurities mixed with the radioactive isotope and extract the radioactive isotope with a smaller amount of extraction solution.

[0058] The radioactive isotope purification apparatus 100 may further include an acidity adjustment unit 6 for adjusting the acidity of the extraction solution containing the radioactive isotope released from the retention / release unit 3. In this case, the acidity adjustment unit 6 can adjust the acidity of the radioactive isotope to be suitable for the synthesis of Ga-labeled compounds.

[0059] The acid concentration of the radioactive isotope-containing solution may be higher than that of the extraction solution. The acid concentration of the radioactive isotope-containing solution is such that it can retain the radioactive isotope in the first resin material, while the concentration of the extraction solution is such that it can elute the radioactive isotope from the first resin material. As a result, when the radioactive isotope-containing solution is supplied to the first resin material, the radioactive isotope is well retained in the first resin material containing a compound with a phosphorus-oxygen bond, impurities are separated, and then the radioactive isotope retained in the first resin material can be well purified.

[0060] Before supplying the extraction solution to the retention / release section 3, a washing solution with a higher acid concentration than the extraction solution may be supplied. The acid concentration of the washing solution is such that radioactive isotopes can be retained from the first resin material, and the concentration of the extraction solution is such that radioactive isotopes can be eluted from the first resin material. This allows for good retention of radioactive isotopes in the first resin material containing a phosphorus-oxygen bond, while removing impurities originating from the radioactive isotope-containing solution, and then effectively purifying the radioactive isotopes retained in the first resin material.

[0061] The radioactive isotope-containing solution and the extraction solution are both hydrochloric acid solutions, and the radioactive isotope-containing solution may have a concentration of 3M to 12M. This ensures that the radioactive isotope is well retained in the first resin material containing a compound with a phosphorus-oxygen bond.

[0062] The radioactive isotope-containing solution and the extraction solution are both hydrochloric acid solutions, and the extraction solution may have a concentration of 0.1 M to 2 M. This allows for effective detachment of the radioactive isotope retained in the first resin material containing a compound having a phosphorus-oxygen bond.

[0063] The first resin material has a volume of 0.1 mL to 2.0 mL and contains a tributyl phosphate compound, and the washing solution is a hydrochloric acid solution with a concentration of 3 to 10 M, and the amount of washing solution may be 10 mL or more. In this case, impurities can be effectively removed from the first resin material.

[0064] The radioactive isotopes contained in the radioactive isotope solution may be produced using an accelerator. In this case, the required amount of radioactive isotope can be obtained at a high yield and when needed.

[0065] A radioactive isotope purification method according to one aspect of the present invention is a radioactive isotope purification method for purifying Ga-68 as a radioactive isotope, wherein a first resin material containing a compound having a phosphorus-oxygen bond is used to retain and release the radioactive isotope, a radioactive isotope-containing solution containing the radioactive isotope is supplied to the first resin material, and an extraction solution is supplied to extract the radioactive isotope retained by the first resin material.

[0066] This radioactive isotope purification method allows for the same effects and functions as the radioactive isotope purification apparatus 100 described above.

[0067] Figure 9(a) is a graph showing the results of a Ga-68 purification experiment related to a radioactive isotope purification apparatus in a comparative example where hydroxamic acid resin (TrisKem ZR resin as a typical commercially available product) was used as the first resin material of the holding / detaching section 3. Figure 9(b) is a graph showing the results of a Ga-68 purification experiment related to a radioactive isotope purification apparatus in Example 1. The purification conditions for Example 1 will now be described. In Example 1, a resin material containing a TBP compound was used as the first resin material of the holding / detaching section 3. When filling the holding / detaching section 3, 6M hydrochloric acid was supplied in a volume of 10 mL. When washing the holding / detaching section 3, 6M hydrochloric acid was supplied in a volume of 30 mL. When extracting from the holding / detaching section 3 (filling into the acidity adjustment section 6), 0.1M hydrochloric acid was supplied in a volume of 20 mL.

[0068] In the horizontal axis of Figure 9, in the first half of the fraction No., a radioactive isotope-containing container is supplied to the holding / detachment section 3, and hydrochloric acid is supplied as a washing solution. In Figure 9(a), hydrochloric acid is supplied as an extraction solution to the holding / detachment section 3 at the timing of fraction No. 30-40, and in Figure 9(b), at the timing of fraction No. 40-50. The amount of solution supplied in each fraction is kept constant. The vertical axis of Figure 9 shows the amount of metal ions released from the holding / detachment section 3. As shown in Figures 9(a) and 9(b), in Example 1, the extraction of Fe and Zn is completed in fewer fraction No. than in the comparative example. Also, in the comparative example in Figure 9(a), the extraction of Ga-68 is completed in 3-4 fractions, whereas in Example 1 in Figure 9(b), the extraction of Ga-68 is completed in 1 fraction. Thus, in Example 1, it can be confirmed that impurities can be removed with a small amount of solution, and that Ga-68 can be extracted with a small amount of extraction solution. If impurities can be removed and Ga-68 extracted using a small amount of solution, it becomes easier to control the concentration of Ga-68.

[0069] (Example 2) Next, Example 2 will be described. In Example 2, the purification efficiency by manual procedure was confirmed. Here, a small amount of Ga-68 was produced using an accelerator, and a separation and purification test was performed by manual procedure. The purification conditions for Example 2 will be described. As the first resin material for the holding / detaching section 3, a resin material containing a TBP compound was used in a resin volume of 0.3 mL. As the second resin material for the acidity adjustment section 6, a resin material containing a TOPO compound was used in a resin volume of 2.0 mL. When filling the holding / detaching section 3, 10 M hydrochloric acid was supplied in a liquid volume of 6 mL. When washing the holding / detaching section 3, 6 M hydrochloric acid was supplied in a liquid volume of 5 mL. When extracting from the holding / detaching section 3 (filling into the acidity adjustment section 6), 0.5 M hydrochloric acid was supplied in a liquid volume of 5 mL. When washing the acidity adjustment section 6, 0.5 M hydrochloric acid was supplied in a liquid volume of 5 mL. During extraction from the acidity adjustment unit 6, 0.1M hydrochloric acid was supplied in a volume of 3 mL.

[0070] The test results are as follows: The retention rate of radioactive isotopes was 98.7% when filling the retention / release section 3, 99.9% when washing the retention / release section 3, 96.0% when filling the acidity adjustment section 6, and 96.7% when washing the acidity adjustment section 6. The desorption rate (extraction rate) of radioactive isotopes was 91.0% when extracting from the retention / release section 3 and 99.4% when extracting from the acidity adjustment section 6. The overall efficiency was 82.8%.

[0071] The method for confirming the retention rate is described below. When filling the retention / release section 3, the radiation dose A of the solution was measured before filling the resin material, and the radiation dose B of the resin material was measured after the entire solution had been filled into the resin material, and the ratio of radiation dose B to radiation dose A was calculated. When cleaning the retention / release section 3, the radiation dose B of the resin material was measured after the entire solution had been filled into the resin material, and the radiation dose C of the resin material was measured after cleaning, and the ratio of radiation dose C to radiation dose B was calculated. When extracting from the retention / release section 3, the radiation dose C of the resin material was measured after cleaning, and the radiation dose D of the solution extracted from the retention / release section 3 was measured, and the ratio of radiation dose D to radiation dose C was calculated. The method for confirming the retention rate for the acidity adjustment section 6 was the same as for the retention / release section 3. Note that the above radiation doses are measured values ​​that have been attenuated to reflect the radiation dose at the same time.

[0072] (Example 3) Example 3 will now be described. In this purification process, Ga-68 of the scale actually used in drug manufacturing was produced using an accelerator, and the conditions for the liquid volume were determined to keep the amount of Zn and Fe metal contamination below the standard values ​​specified in the European Pharmacopoeia.

[0073] The purification conditions for Example 3 are described below. As the first resin material for the retaining / detaching section 3, a resin material containing a TBP compound was used in a volume of 0.3 mL. As the second resin material for the acidity adjustment section 6, a resin material containing a TOPO compound was used in a volume of 2.0 mL. When filling the retaining / detaching section 3, 10M hydrochloric acid was supplied in a volume of 10 mL. When washing the retaining / detaching section 3, 6M hydrochloric acid was supplied in a volume of 10 mL. When extracting from the retaining / detaching section 3 (filling into the acidity adjustment section 6), 0.5M hydrochloric acid was supplied in a volume of 5 mL. When washing the acidity adjustment section 6, 0.5M hydrochloric acid was supplied in a volume of 5 mL. When extracting from the acidity adjustment section 6, 0.1M hydrochloric acid was supplied in a volume of 3 mL.

[0074] The test results are as follows: When the amount of metal ions in the extract from the acidity adjustment unit 6 was measured, the amount of Fe was 0.38 (μg / GBq), which met the condition of being less than the European Pharmacopoeia standard of 10 (μg / GBq). The amount of Zn was 0.75 (μg / GBq), which also met the condition of being less than the European Pharmacopoeia standard of 10 (μg / GBq). Thus, the results met the metal ion contamination standards specified in the European Pharmacopoeia.

[0075] The present invention is not limited to the embodiments described above.

[0076] In the embodiments described above, a radioisotope-containing solution containing radioisotopes produced using a cyclotron is used, but the method for producing the radioisotopes contained in the radioisotope-containing solution is not limited to this. For example, any radioisotopes produced using an accelerator such as a cyclotron, synchrotron, or synchrocyclotron may be used.

[0077] Figure 10 is a conceptual diagram of a radiopharmaceutical production system including a radioisotope purification system using an accelerator. In the production of radioisotopes using particle beams such as cyclotrons, Zn-68 is used as a raw material. When a particle beam is irradiated onto a Zn-68 target, Ga-68 is produced, while Zn as an impurity is mixed with the Ga-68. The radioisotope purification apparatus 100 of the present invention is used to remove this impurity.

[0078] As shown in Figure 10, the radioactive isotope purification system 200 comprises an accelerator 101, a dissolution device 102, and a radioactive isotope purification device 100. The radioactive drug production system 301 comprises the radioactive isotope purification system 200 and a labeling synthesis device 103. The accelerator 101 irradiates solid Zn-68 with protons accelerated by the accelerator 101, producing Ga-68 through a nuclear reaction. In the path from the accelerator 101 to the dissolution device 102, the irradiated target is transported mechanically or by human transport and fed into (installed) the dissolution device 102. The dissolution device 102 dissolves the irradiated Zn-68 with hydrochloric acid to obtain a hydrochloric acid solution. This solution is then transferred to the radioactive isotope purification device 100. The radioactive isotope purification device 100 separates and purifies Ga-68 using the configuration according to the above embodiment. The purified Ga-68 solution is transferred to the labeling synthesis apparatus 103. The labeling synthesis apparatus 103 uses the purified Ga-68 solution to synthesize the labeled drug.

[0079] On the other hand, as a comparative embodiment, a radiopharmaceutical production system 302 using a generator will be described. Figure 11 is a conceptual diagram of a radiopharmaceutical production system using a generator. In the production of a radioisotope solution using a generator, Ge-68 held in a column is used as a raw material. Over time, Ge-68 decays into Ga-68. Since this generated Ga-68 has low retention capacity in the column, it can be easily isolated and extracted, for example, with 0.1 M hydrochloric acid. The Ga-68 solution produced by the generator is less likely to be contaminated with impurities that would be a problem in subsequent processes under normal usage, so it is not necessary to perform a new purification process on the obtained Ga-68 in subsequent processes.

[0080] As shown in Figure 11, the radiopharmaceutical production system 302 comprises a generator 201 and a labeling synthesis device 203. In the generator 201, Ge-68 held in a column within the generator 201 decays into Ga-68 over time. By flowing dilute hydrochloric acid (0.1M hydrochloric acid) through the resin of the generator 201, Ga-68 is eluted and transported to the labeling synthesis device 203. The labeling synthesis device 203 synthesizes the labeled drug using the purified Ga-68 solution.

[0081] When producing radioactive isotopes using an accelerator, it is possible to obtain radioactive isotopes in high yields (radiation dose: several GBq to tens of GBq), and there is the advantage of being able to produce the required amount when needed. However, purification is required each time, but this invention makes it possible to purify them efficiently and to a high degree of purity.

[0082] When producing radioactive isotopes using a generator, there is no need for an in-hospital cyclotron, and a solution usable for labeling can be obtained simply by flowing dilute hydrochloric acid without any special chemical operations. On the other hand, there are disadvantages such as low yield (several hundred MBq to slightly over 1 GBq) and limitations on the number of milking (extracting radioactive isotopes from the generator) operations per day. Another disadvantage is that Ge-68 continues to decay even when not in use. These disadvantages can be avoided when using an accelerator.

[0083] The piping for transporting the radioactive isotope-containing solution, washing solution, and extractant is preferably made of a resin that is resistant to the radioactive isotope-containing solution, although this is not limited to such piping. "Resistant" means that the resin does not lose its physical properties upon contact with the radioactive isotope-containing solution. When the solvent in the solution is hydrochloric acid, suitable materials for the piping include, for example, polyether ether ketone (PEEK), fluororesin, polyphenylene sulfide (PPS), etc.

[0084] In the radioactive isotope purification system 200 shown in Figure 10, Ga-68 is produced using a solid Zn-68 target; however, radioactive isotopes may also be produced using a liquid target, for example. Furthermore, the structure of the radioactive isotope purification apparatus shown in Figure 1 is merely an example and may be modified as appropriate.

[0085] [Form 1] A radioisotope purification apparatus for purifying Ga-68 as a radioisotope, comprising a holding and releasing section for holding and releasing the radioisotope using a first resin material containing a compound having a phosphorus-oxygen bond, A radioisotope purification apparatus comprising supplying a radioisotope-containing solution containing the radioisotope to the holding and releasing section, and supplying an extraction solution to the holding and releasing section for extracting the radioisotope held therein. [Form 2] The radioisotope purification apparatus according to Embodiment 1, wherein the first resin material has a compound of "(R1O)(R2O)(R3O)PO", and R1, R2, and R3 are a linear alkyl group having 2 to 8 carbon atoms, a branched alkyl group having 3 to 8 carbon atoms, a hydrocarbon group having 3 to 8 carbon atoms with an unsaturated bond, or an aromatic group. [Form 3] The radioactive isotope purification apparatus according to Embodiment 1, wherein the first resin material comprises any of the following compounds: tributyl phosphate (TBP), diamylamylphosphonic acid (DA[AP]), trioctylphosphine oxide (TOPO), bis(2-ethylhexyl) phosphate (HDEHP), 2-ethylhexyl 2-ethylhexylphosphonic acid-2-ethylhexyl (HEH[EHP]), or bis(2,4,4-trimethylpentyl)phosphinic acid (H[DTMPP]). [Form 4] The radioisotope purification apparatus according to Embodiment 1, wherein the first resin material comprises a compound of tributyl phosphate. [Form 5] A radioisotope purification apparatus according to any one of embodiments 1 to 4, further comprising an acidity adjustment unit for adjusting the acidity of the extraction solution containing the radioisotope released from the holding and releasing unit. [Form 6] The radioactive isotope-containing solution has a higher acid concentration than the extraction solution, according to any one of the embodiments 1 to 5 of the radioactive isotope purification apparatus. [Form 7] A radioactive isotope purification apparatus according to any one of embodiments 1 to 6, wherein a washing solution with a higher acid concentration than the extraction solution is supplied before the extraction solution is supplied to the holding and releasing section. [Form 8] The radioactive isotope-containing solution and the extraction solution are each hydrochloric acid solutions, and the radioactive isotope-containing solution has a concentration of 3M to 12M, according to the radioactive isotope purification apparatus of Embodiment 4. [Form 9] The radioactive isotope-containing solution and the extraction solution are each hydrochloric acid solutions, and the extraction solution has a concentration of 0.1 M to 2 M, according to the radioactive isotope purification apparatus according to form 4 or 8. [Form 10] The radioactive isotope purification apparatus according to Embodiment 7, wherein the first resin material has a volume of 0.1 mL to 2.0 mL and contains a tributyl phosphate compound, the washing solution is a hydrochloric acid solution having a concentration of 3 to 10 M, and the amount of the washing solution is 10 mL or more. [Form 11] The radioactive isotope contained in the radioactive isotope solution is produced using an accelerator, and is a radioactive isotope purification apparatus according to any one of the embodiments 1 to 10. [Form 12] A method for purifying radioactive isotopes, wherein Ga-68 is purified as a radioactive isotope, A first resin material containing a compound having a phosphorus-oxygen bond is used to retain and release the radioactive isotope. A radioactive isotope-containing solution containing the aforementioned radioactive isotope is supplied to the first resin material. An extraction solution is supplied for extracting the radioactive isotope held in the first resin material. Radioisotope purification method. [Explanation of Symbols]

[0086] 1...Fluid supply unit, 2...Fluid control unit, 3...Holding and releasing unit, 6...Acidity adjustment unit, 100...Radioactive isotope purification device.

Claims

1. A radioisotope purification apparatus for purifying Ga-68 as a radioisotope, comprising a holding and releasing section for holding and releasing the radioisotope using a first resin material containing a compound having a phosphorus-oxygen bond, A radioactive isotope-containing solution containing the radioactive isotope is supplied to the holding and releasing section, and an extraction solution for extracting the radioactive isotope held in the holding and releasing section is supplied. The first resin material has a compound of "(R1O)(R2O)(R3O)PO", where R1, R2, and R3 are linear alkyl groups having 2 to 8 carbon atoms, branched alkyl groups having 3 to 8 carbon atoms, hydrocarbon groups having 3 to 8 carbon atoms with unsaturated bonds, or aromatic groups, and is a radioisotope purification apparatus.

2. A radioisotope purification apparatus for purifying Ga-68 as a radioisotope, comprising a holding and releasing section for holding and releasing the radioisotope using a first resin material containing a compound having a phosphorus-oxygen bond, A radioactive isotope-containing solution containing the radioactive isotope is supplied to the holding and releasing section, and an extraction solution for extracting the radioactive isotope held in the holding and releasing section is supplied. The first resin material is a radioisotope purification apparatus having a tributyl phosphate compound.

3. The radioisotope purification apparatus according to claim 1 or 2, further comprising an acidity adjustment unit for adjusting the acidity of the extraction solution containing the radioisotope released from the holding and releasing unit.

4. The radioactive isotope purification apparatus according to claim 1 or 2, wherein the radioactive isotope-containing solution has a higher acid concentration than the extraction solution.

5. The radioactive isotope purification apparatus according to claim 2, wherein the radioactive isotope-containing solution and the extraction solution are each hydrochloric acid solutions, and the radioactive isotope-containing solution has a concentration of 3 M to 12 M.

6. The radioactive isotope purification apparatus according to claim 2, wherein the radioactive isotope-containing solution and the extraction solution are each hydrochloric acid solutions, and the extraction solution has a concentration of 0.1 M to 2 M.

7. The radioactive isotope purifying apparatus according to claim 1 or 2, wherein the radioactive isotope contained in the radioactive isotope-containing solution is produced using an accelerator.

8. A radioisotope purification apparatus for purifying Ga-68 as a radioisotope, comprising a holding and releasing section for holding and releasing the radioisotope using a first resin material containing a compound having a phosphorus-oxygen bond, A radioactive isotope-containing solution containing the radioactive isotope is supplied to the holding and releasing section, and an extraction solution for extracting the radioactive isotope held in the holding and releasing section is supplied. Before supplying the extraction solution to the holding and releasing section, a washing solution with a higher acid concentration than the extraction solution is supplied. A radioactive isotope purification apparatus comprising the first resin material having a volume of 0.1 mL to 2.0 mL and containing a tributyl phosphate compound, the washing solution being a hydrochloric acid solution having a concentration of 3 to 10 M, and the amount of the washing solution being 10 mL or more.

9. A method for purifying radioactive isotopes, comprising purifying Ga-68 as a radioactive isotope, A first resin material containing a compound having a phosphorus-oxygen bond is used to hold and release the radioactive isotope in a holding / releasing section. A radioactive isotope-containing solution containing the aforementioned radioactive isotope is supplied. An extraction solution for extracting the radioactive isotope held in the first resin material is supplied. A method for purifying radioisotopes, wherein the first resin material has a compound of "(R1O)(R2O)(R3O)PO", and R1, R2, and R3 are a linear alkyl group having 2 to 8 carbon atoms, a branched alkyl group having 3 to 8 carbon atoms, a hydrocarbon group having 3 to 8 carbon atoms with an unsaturated bond, or an aromatic group.

10. A method for purifying radioactive isotopes, comprising purifying Ga-68 as a radioactive isotope, A first resin material containing a compound having a phosphorus-oxygen bond is used to hold and release the radioactive isotope in a holding / releasing section. A radioactive isotope-containing solution containing the aforementioned radioactive isotope is supplied. An extraction solution for extracting the radioactive isotope held in the first resin material is supplied. The first resin material is a compound of tributyl phosphate, and the method for purifying radioactive isotopes.

11. A method for purifying radioactive isotopes, comprising purifying Ga-68 as a radioactive isotope, A first resin material containing a compound having a phosphorus-oxygen bond is used to hold and release the radioactive isotope in a holding / releasing section. A radioactive isotope-containing solution containing the aforementioned radioactive isotope is supplied. An extraction solution for extracting the radioactive isotope held in the first resin material is supplied. Before supplying the extraction solution to the holding and releasing section, a washing solution with a higher acid concentration than the extraction solution is supplied. A method for purifying radioactive isotopes, wherein the first resin material has a volume of 0.1 mL to 2.0 mL and contains a tributyl phosphate compound, the washing solution is a hydrochloric acid solution having a concentration of 3 to 10 M, and the amount of the washing solution is 10 mL or more.

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