Shaking mixer and method for treating pet nuclides

Abstract

To provide a shaking mixer that can safely mix radionuclides and labeling drugs.SOLUTION: A shaking mixer 10 shakes a vial 20 containing a PET nuclide and a labeling drug. The shaking mixer 10 includes: a base 12 that holds a motor with a motor shaft facing upward; a resin column 14 that has an axial hole into which the motor shaft is inserted on one end and a protrusion 143 on the other end; and a resin cylinder 11 that extends coaxially with the motor shaft from the base 12 beyond a tip of the protrusion.SELECTED DRAWING: Figure 5

Description

[Technical field]

[0001] The present invention relates to a shaker / agitator and a method for treating PET nuclides. [Background technology]

[0002] In PET (Positron Emission Tomography) examinations, a PET drug containing a radioactive nuclide is administered to the patient's blood vessels, and after the patient has rested for a period of time, the distribution of the radioactive nuclide in the body is photographed. The patient must remain in a radiation-controlled area until the radioactivity of the administered PET drug has sufficiently decayed. Therefore, it is preferable to use a radioactive nuclide with a short half-life for the PET drug.

[0003] PET drugs that use nuclides with short half-lives have a short usable period after production. Therefore, it is desirable to produce PET drugs within medical institutions whenever they are needed. A generator has been proposed that produces short-half-life radionuclides for PET examinations from parent nuclides with relatively long half-lives (Patent Document 1). Since no large equipment such as a cyclotron is used, the radionuclides required for the production of PET drugs can be produced within a medical institution, for example. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2010-195777 A Summary of the Invention [Problem to be solved by the invention]

[0005] PET drugs can be produced by binding the radionuclides produced by the generator of Patent Document 1 to target molecules that tend to accumulate in diseased areas. However, when the process of mixing the radionuclides and the labeling drug containing the target molecules is performed manually, there is a risk of exposure to radiation for the workers.

[0006] In one aspect, an object of the present invention is to provide a shaking mixer capable of safely mixing radioactive nuclides and labeling drugs. [Means for solving the problem]

[0007] The shaking stirrer shakes the vials containing the PET nuclide and the labeling agent. Effect of the Invention

[0008] In one aspect, a shaking mixer capable of safely mixing radionuclides and labeling agents can be provided. [Brief description of the drawings]

[0009] [Figure 1] FIG. 1 is an explanatory diagram illustrating a manufacturing procedure for a PET drug. [Diagram 2] FIG. [Diagram 3] FIG. 3 is an enlarged partial cross-sectional view of a portion III in FIG. [Figure 4] FIG. [Diagram 5] FIG. 13 is an explanatory diagram illustrating the state of a vial during stirring. [Figure 6] FIG. 13 is an explanatory diagram illustrating the state of a vial during stirring. [Figure 7] This is a modified example of a column. [Figure 8] This is a modified example of a column. [Figure 9] FIG. 11 is a three-sided view of a shaking mixer according to a second embodiment. [Figure 10] FIG. 11 is a front view of a shaking mixer according to a third embodiment. [Figure 11] FIG. 11 is a vertical cross-sectional view of a shaking mixer according to a third embodiment. [Figure 12] 12 is a cross-sectional view taken along line XII-XII in FIG. 10. [Figure 13] 1 is a half cross-sectional view and a bottom view of a cylinder, an upper support plate, and a lower support plate. [Figure 14] FIG. 11 is an explanatory diagram for explaining the configuration of a shaking mixer according to a third embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] [Embodiment 1] Figure 1 is an explanatory diagram explaining the manufacturing procedure of a PET drug. A labeling drug containing a target molecule is contained in a vial 20 in a sterile state. The vial 20 is a small glass bottle sealed with a rubber stopper. The rubber stopper can be pierced with a needle multiple times.

[0011] In this embodiment, the target molecule is a molecule that reacts with the radioactive nuclide 68Ga (gallium 68) to generate a 68Ga-PSMA (Prostate Specific Membrane Antigen) specific ligand, which is a PET drug, as an example. 68Ga is an example of the PET nuclide in this embodiment.

[0012] PSMA is a molecule that is overexpressed on the surface of several types of cancer cells, including prostate cancer cells. PSMA-specific ligands are substances that specifically bind to the surface of cancer cells that overexpress PSMA. By administering 68Ga-PSMA-specific ligands to patients and having them rest for a while, the 68Ga-PSMA-specific ligands accumulate on the surface of cancer cells that overexpress PSMA. By imaging using a PET examination device in this state, the distribution of locations where radiation is being emitted from 68Ga, that is, the distribution of cancer cells that overexpress PSMA, can be imaged. Therefore, it is possible to diagnose the presence or absence of prostate cancer, the size of the lesion, and the location of metastasis.

[0013] The shaking mixer 10 has a main body 15 placed horizontally on a desk or workbench, a base 12 placed on the top surface of the main body 15, and a cylindrical body 11 placed on the top surface of the base 12. A user inserts a vial 20 into the cylindrical body 11. By using a light-transmitting material for the cylindrical body 11, the user can visually confirm the state of stirring, which will be described later. The internal configuration of the cylindrical body 11 will be described later.

[0014] One surface of the main body 15 is inclined with respect to the upper surface, and an ON / OFF switch 18 for ON-OFF operation is disposed thereon. For example, a liquid crystal display panel displaying the operating status of the shaker / mixer 10 may be disposed on the inclined portion. A touch panel displaying buttons or the like having the function of the ON / OFF switch 18 may be disposed on the inclined portion.

[0015] The generator 30 is a device that generates radionuclides suitable for PET drugs. The generator 30 contains a parent nuclide, which is a radionuclides with a relatively long half-life. The decay of the parent nuclide produces a daughter nuclide with a short half-life. A specific example will be given to explain. The parent nuclide is 68Ge (germanium 68), which has a half-life of 271 days. The decay of 68Ge produces 68Ga, which has a half-life of 68 minutes.

[0016] A supply tube 31 that supplies the generated liquid containing 68Ga to the outside is connected to the generator 30. A needle (not shown) is attached to the tip of the supply tube 31. The user pierces the rubber stopper of the vial 20 with the needle of the supply tube 31.

[0017] The user then inserts the vent needle 36 into the rubber stopper of the vial 20. The tip of the vent needle 36 is positioned above the liquid level of the combined labeling agent and 68Ga solution in the vial 20. If the inside of the vial 20 is adjusted to a negative pressure, it is not necessary to use the vent needle 36.

[0018] The user operates the ON / OFF switch 18 to turn the shaking mixer 10 ON. Shaking of the vial 20 begins. The configuration for shaking the vial 20 will be described later. The user then operates the start switch provided on the generator 30 to begin supplying 68Ga from the tip of the supply tube 31 into the vial 20. Air equivalent to the volume of the liquid supplied to the inside of the vial 20 through the supply tube 31 is pushed out of the vial 20 by the ventilation needle 36.

[0019] The labeling agent and 68Ga in the vial 20 are shaken to generate a 68Ga-PSMA specific ligand, which is a PET drug. The generated PET drug is promptly administered to a patient undergoing a PET examination.

[0020] By using the shaking mixer 10 of this embodiment, the user does not need to touch the vial 20 during shaking and mixing, so that the user's exposure to radiation can be prevented. Since the vial 20 is shaken while the supply tube 31 is connected, the radioactive nuclide can be supplied to the vial 20 little by little while shaking and mixing. Therefore, it is possible to provide a shaking mixer 10 that reliably reacts 68Ga with the labeling drug.

[0021] The operations of inserting the supply tube 31 and the vent needle 36 into and removing the rubber stopper of the vial 20 may be performed using a robot or an automated machine. By reducing the chances of the user coming into contact with radioactive nuclides, the user's exposure can be prevented.

[0022] 2 is a three-view diagram of the shaking mixer 10. In the following description, the lower left diagram in FIG. 2 is referred to as a front view, the upper left diagram as a plan view, and the lower right diagram as a right side view. In the front view, a part of the cylinder 11 is cut away to show the internal structure of the cylinder 11.

[0023] Fig. 3 is an enlarged partial cross-sectional view of part III in Fig. 2. Fig. 3 shows a cross-section of the columnar body 14. As shown in Fig. 3, the motor 13 is held on the base 12 with the motor shaft 131 facing upward. The structure for fixing the base 12 and the motor 13 is not shown. The motor shaft 131 and the cylindrical body 11 are disposed approximately coaxially. The motor 13 is, for example, a DC motor that rotates at a constant speed.

[0024] A pillar 14 is fixed to the motor shaft 131. The pillar 14 has a shape in which the end of a cylinder is cut off at an angle with respect to the central axis. The shape of the pillar 14 will be described in detail later. The motor shaft 131 and the pillar 14 are fixed coaxially. Therefore, as shown in the plan view of FIG. 2, the cylindrical body 11 and the pillar 14 are arranged coaxially.

[0025] The end of the cylinder 11 is located higher than the tip of the pillar 14. That is, the cylinder 11 extends from the base 12 farther than the tip of the pillar 14. The cylinder 11 and the motor shaft 131 are coaxial. The tip of the pillar 14 is located away from the central axis of the motor shaft 131.

[0026] 4 is a three-view diagram of the cylinder 14. The cylinder 14 has a shape in which a protrusion 143 having a shape obtained by cutting a cylinder having the same diameter as the cylinder portion 145 obliquely by an inclined surface 142 is connected to an end face of the cylinder portion 145. An axial hole 141 coaxial with the cylinder portion 145 is provided in the other end face of the cylinder portion 145. The axial hole 141 does not penetrate the cylinder 14. The tip of the protrusion 143 is located at a position away from the central axis of the axial hole 141.

[0027] The inner diameter of the shaft hole 141 is slightly smaller than the outer diameter of the motor shaft 131, and the pillar 14 and the motor shaft 131 are fixed together by pushing the motor shaft 131 into the shaft hole 141. Therefore, when the motor shaft 131 is rotated, the pillar 14 rotates integrally with the motor shaft 131.

[0028] A rotation prevention structure such as a key and a key groove may be provided in the shaft hole 141 and the motor shaft 131. The shaft hole 141 and the motor shaft 131 may be fixed to each other with an adhesive or a pressure sensitive adhesive.

[0029] The cylinder 11 and the columnar body 14 are made of a resin material with high sliding properties, such as hard polyethylene, polypropylene, polyetheretherketone (PEEK), polytetrafluoroethylene (PTFE), etc. The material of the cylinder 11 and the material of the columnar body 14 may be different.

[0030] 5 and 6 are explanatory diagrams for explaining the state of the vial 20 during stirring. Because the pillar 14 has the protrusion 143, the vial 20 is placed on the pillar 14 in an inclined state. The inclination angle is about 5 degrees. As shown in part A, the bottom of the vial 20 contacts the tip of the protrusion 143. As shown in part B, the side of the vial 20 contacts the inner end face of the cylinder 11. Depending on the state of inclination, the edge of the bottom of the vial 20 may contact the inner face of the cylinder 11 as shown in part C.

[0031] By operating motor 13 to rotate motor shaft 131, cylinder 14 also rotates. Table 1 shows the results of an experiment on the relationship between the rotation speed of motor 13 and the shaking and stirring effect. The unit of rotation speed is rpm (revolutions per minute). A shaking and stirring result of "good" indicates that the contents of vial 20 were sufficiently permeated and stirred with almost no rotational movement of vial 20 itself. A result of "poor" indicates that the shaking and stirring of the contents of vial 20 was insufficient, regardless of the presence or absence of rotational movement of vial 20.

[0032] [Table 1]

[0033] The vial 20 used in the experiment shown in Table 1 is an ISO standard vial (15R) with an outer diameter of 24 mm, a height of 60 mm, and a full capacity of 19 ml. The radius of the cylinder 14, i.e., the distance from the central axis of the motor shaft 131 to the contact point between the vial 20 and the shaft hole 141, is 4 mm.

[0034] The cylinder 11 has an inner diameter of 28 mm. Therefore, the distance from the center axis of the motor shaft 131 to the contact point between the vial 20 and the cylinder 11 is 14 mm at both parts B and C shown in FIG.

[0035] The experiment shown in Table 1 was carried out with the vial 20 filled with water up to 80%. The experiment shown in Table 1 was carried out with the supply tube 31 not connected to the vial 20.

[0036] As shown in Table 1, a good shaking and stirring effect can be obtained by rotating the cylinder 14 at an appropriate rotation speed. If the rotation speed is too fast or too slow, the shaking and stirring effect cannot be obtained. Therefore, for example, when the amount of liquid contained in the vial 20 varies, it is desirable to provide the shaking and stirring machine 10 with a dial or the like for adjusting the rotation speed and to determine an appropriate rotation speed through prior consideration.

[0037] The following is an outline of the mechanism by which the shaking / stirring device 10 of this embodiment exerts the shaking / stirring effect. For example, when the static friction force between the vial 20 and the protrusion 143 is sufficiently large at part A in FIG. 5, the vial 20 rotates without slippage between the vial 20 and the protrusion 143. In this case, slippage or rolling occurs between the vial 20 and the cylindrical body 11 at parts B and C. That is, a sliding friction force or a rolling friction force acts on the vial 20 at parts B and C.

[0038] However, since there are slight irregularities on the surface of the vial 20 and on the inside of the end face of the cylindrical body 11, the sliding friction force or rolling friction force generated between the vial 20 and the cylindrical body 11 is not constant. In a place where the friction force between the vial 20 and the cylindrical body 11 is large, the friction force between the vial 20 and the protrusion 143 is small. Therefore, slippage occurs between the vial 20 and the protrusion 143.

[0039] Since there are slight irregularities on the bottom surface of the vial 20, the sliding friction force between the protrusion 143 and the vial 20 is not constant. In places where the sliding friction force between the vial 20 and the protrusion 143 is large, the state where no sliding occurs between the protrusion 143 and the vial 20 again occurs, and a static friction force larger than the sliding friction force acts.

[0040] By repeatedly causing slippage between the protrusion 143 and the vial 20 and causing no slippage, the vial 20 swings around inside the cylinder 11 with almost no rotation as shown in Figures 5 and 6, and the liquid inside is shaken and stirred.

[0041] Furthermore, the supply tube 31 connected to the lid of the vial 20 also prevents the vial 20 from rotating together with the columnar body 14. As described above, it is possible to provide a vibration mixer 10 that shakes and mixes the liquid in the vial 20 while the supply tube 31 and the vial 20 are connected. Note that the user may operate the motor 13 after removing the supply tube 31 from the vial 20. By removing the supply tube 31, the vibration mixer 10 can be used even under conditions where the vial 20 rotates.

[0042] As described above, since the cylindrical body 11 and the columnar body 14 are made of resin, even if slippage occurs between the vial 20 and the cylindrical body 11 and the columnar body 14, the surface of the vial 20 will not be scratched. Therefore, scratches on the vial 20 during shaking and stirring and cracking of the vial 20 due to scratches can be prevented.

[0043] Since the vial 20 is supported by the cylindrical body 11 and swings at an inclination of about 5 degrees, the liquid surface in the vial 20 swings less than when the vial 20 is shaken up and down to stir, for example. Therefore, a shaking mixer 10 that is less likely to generate bubbles in the liquid in the vial 20 can be provided.

[0044] Since the structure is simple, in which shaking and stirring of vial 20 can be achieved simply by rotating motor 13 in one direction, an inexpensive DC motor and a simple control circuit that drives the DC motor at a constant voltage can be used to provide an inexpensive shaking and stirring machine 10 that is less likely to break down.

[0045] A switch for reversing the rotation of motor 13 may be provided near ON / OFF switch 18. For example, the user may rotate motor 13 clockwise to shake and stir, and then rotate it counterclockwise to shake and stir again.

[0046] A timer switch for setting the operation time of the motor 13 may be provided near the ON / OFF switch 18. The shaker / mixer 10 may have a function of automatically stopping the motor 13 when a predetermined time has elapsed after starting the rotation of the motor 13 in response to the user's operation of the ON / OFF switch 18.

[0047] The cylinder 11 may be replaceable. A user can replace the cylinder 11 depending on, for example, the height of the vial 20 to be used.

[0048] When using a resin vial 20, the cylinder 11 and the column 14 may be made of a hard material such as metal, glass, or ceramics. Although scratches may occur on the surface of the vial 20 during stirring and shaking, the PET drug is quickly taken out of the vial 20 after stirring and shaking and administered to the patient, so scratches do not cause any particular problems.

[0049] The radionuclide is not limited to 68Ga. The target molecule may be a molecule that reacts with the radionuclide 64Cu (copper 64) to generate a 64Cu-PSMA specific ligand, which is a PET drug. The target molecule may be a molecule that reacts with the radionuclide 89Zr (zirconium 89) to generate a Zr89-PSMA specific ligand, which is a PET drug.

[0050] Molecules labeled with radionuclides are not limited to PSMA-specific ligands. For example, the target molecule may be a molecule that reacts with the radionuclide 18F (fluorine 18) to generate 18F-FDG (fluorodeoxyglucose F18), a PET drug. 18F-FDG accumulates in tissues that consume a lot of glucose, including cancer cells. FDG-PET, which images the location of 18F-FDG accumulation, has been used for detecting cancer and determining recurrence after treatment.

[0051] Additionally, the shaker 10 of the present embodiment can be used to manufacture PET drugs combining any radionuclide with any targeting molecule. For example, the targeting molecule can be DOTATOC acetate, a molecule that reacts with 68Ga to produce the PET drug 68Ga-DOTATOC, a synthetic somatostatin analog that binds to somatostatin receptors that are overexpressed in neuroendocrine tumors.

[0052] The PET drug produced using the shaking mixer 10 of this embodiment may be, for example, a molecule that produces 64Cu-ATSM (64Cu-diacetyl-bis (N4-methylthiosemicarbazone). 64Cu-ASTM accumulates in cells and tissues in a hypoxic state, such as cancer cells. 64Cu-ASTM is also known to have the effect of killing cancer cells in the area where it accumulates.

[0053] The PET agent may be, for example, 89Zr-desferrioxamine B. The PET agent may be a monoclonal antibody labeled with a radionuclide such as 89Zr.

[0054] The shaker 10 may be used to produce a SPECT (Single Photon Emission Computed Tomography) agent. For example, the radionuclide may be 111In (Indium 111) and the target molecule may be a molecule that reacts with 111In to produce the SPECT agent Indium pentetreotide.

[0055] The shaker 10 may be used to manufacture a bone scintigraphy agent. For example, the radionuclide may be 99mTc (technetium 99m: a metastable nuclear isomer of technetium) and the target molecule may be a molecule that reacts with 99mTc to produce the bone scintigraphy agent technetium hydroxymethylenediphosphonate.

[0056] In addition, the shaker / mixer 10 may be used to manufacture any RI (Radio Isotope) testing agent.

[0057] The shaker 10 may be used to manufacture radiotherapy drugs. For example, the radionuclide may be 177Lu (lutetium 177), and the target molecule may be a molecule that reacts with 177Lu to generate a lutetium 177-labeled PSMA-specific ligand. The lutetium 177-labeled PSMA-specific ligand accumulates in prostate cancer cells that overexpress PSMA and emits gamma and beta rays that are capable of killing the cells. Thus, localized radiotherapy of prostate cancer can be performed.

[0058] The radionuclide may be 211At (astatine 211), and the target molecule may be a molecule that reacts with 211At to generate an astatine 211-labeled PSMA-specific ligand. The astatine 211-labeled PSMA-specific ligand accumulates in prostate cancer cells that overexpress PSMA and emits alpha rays that are capable of killing the cells. Thus, localized radiotherapy of prostate cancer can be performed.

[0059] The radionuclide may be 255Ac (actinium 255), and the target molecule may be a molecule that reacts with 255Ac to generate an actinium 255-labeled PSMA-specific ligand. The actinium 255-labeled PSMA-specific ligand accumulates in prostate cancer cells that overexpress PSMA and emits alpha rays that are capable of killing the cells. Thus, localized radiotherapy of prostate cancer can be performed.

[0060] [Variation 1] 7 shows a modified example of the cylinder 14. In the cylinder 14 of this modified example, a cylindrical projection 143 is disposed on a top surface 144 which is one end surface of a cylindrical portion 145. The cylindrical portion 145 and the projection 143 are not coaxial. The vial 20 inserted into the cylindrical body 11 is held in an inclined state by the projection 143.

[0061] [Variation 2] 8 shows a modified example of the cylinder 14. In the cylinder 14 of this modified example, a hemispherical protrusion 143 is disposed on the top surface 144 of a cylindrical portion 145. The cylindrical portion 145 and the protrusion 143 are not coaxial. The vial 20 inserted into the cylindrical body 11 is held in an inclined state by the protrusion 143.

[0062] According to this embodiment, it is possible to provide a shaking mixer 10 that can reduce the risk of radiation exposure to the user and safely mix the radioactive nuclide and the labeled drug.

[0063] According to this embodiment, it is possible to provide a shaking mixer 10 that can be used with the supply tube 31 connected to the vial 20. For example, it is possible to provide a shaking mixer 10 that produces PET pharmaceuticals of stable quality by supplying radioactive nuclides little by little from the generator 30 to the vial 20 while stirring.

[0064] Instead of the generator 30, for example a container containing a solution containing a radioactive nuclide may be connected to the supply tube 31.

[0065] [Embodiment 2] This embodiment relates to a shaker / mixer 10 having a structure that blocks radiation. Explanation of parts common to the first embodiment will be omitted.

[0066] 9 is a three-view diagram of the shaking mixer 10 of the embodiment 2. The outer periphery of the cylinder 11 is covered with a radiation shielding body 40. The radiation shielding body 40 is a rectangular parallelepiped having a cylindrical through-hole in the center. The radiation shielding body 40 is made of, for example, tungsten, lead, or iron.

[0067] The radiation shield 40 may be cylindrical. Alternatively, the radiation shield 40 may have any other outer shape.

[0068] According to this embodiment, it is possible to provide a shaking and mixing machine 10 that is shielded from radiation during shaking and mixing, thereby further reducing the risk of exposure to radiation for the user.

[0069] [Embodiment 3] This embodiment relates to a shaker mixer 10 that heats a vial 20 during stirring. Explanations of parts common to embodiment 1 will be omitted. When a target molecule has a chelate ring, it is known that the reaction between the target molecule and a radioactive nuclide proceeds efficiently by heating to a temperature of about 80°C to 95°C.

[0070] Fig. 10 is a front view of the vibration mixer 10 of the embodiment 3. In Fig. 10, the supply tube 31 and the ventilation needle 36 are omitted. The vibration mixer 10 of the present embodiment includes a main body 15 having a substantially rectangular parallelepiped shape and a cylindrical body 11 attached to the top side of the main body 15.

[0071] 10, a temperature display unit 521, a display 55, a display changeover switch 551, a speed adjustment dial 561, a speed changeover switch 562, a direction switch 563, and an ON / OFF switch 18 are arranged on one side of the main body 15. These switches and the like may be distributed and arranged on multiple sides.

[0072] On the other side (not shown), an inlet used for supplying power and a main power switch used for turning on and off the power supply from the inlet to the shaker / mixer 10 are arranged.

[0073] Fig. 11 is a vertical cross-sectional view of the shaker mixer 10 of the embodiment 3. Fig. 12 is a cross-sectional view taken along line XII-XII in Fig. 10. In Fig. 11, the internal structure of the main body 15, the supply tube 31, and the ventilation needle 36 are omitted.

[0074] As shown in Fig. 11, motor 13 is fixed to the upper part of main body 15. That is, the upper part of main body 15 in this embodiment also functions as base 12 described in embodiment 1. Motor 13 is arranged with motor shaft 131 facing upward, as in embodiment 1. Pillar body 14 is fixed to motor shaft 131. Screw holes are provided in main body 15 at approximately 90 degree intervals around motor shaft 131.

[0075] The cylinder 11 is composed of three cylinders, an inner cylinder 111, an outer cylinder 112, and a protective cylinder 113, in that order from the inside. Both ends of the inner cylinder 111, the outer cylinder 112, and the protective cylinder 113 are held by an upper holding plate 431 and a lower holding plate 432. The upper holding plate 431 and the lower holding plate 432 are provided with four through holes spaced at approximately 90 degree intervals. A temperature sensor 51 is embedded in the outer cylinder 112. The temperature sensor 51 is, for example, a thermocouple. The configuration of the cylinder 11 will be described in detail later.

[0076] An annular lid 42 is disposed on the upper side of the cylindrical body 11. A tapered hole that widens upward is provided in the center of the lid 42. The outer edge of the lid 42 is bent downward at approximately 90 degrees. The lid 42 has four through holes spaced approximately 90 degrees apart. The upper part of each through hole is deeply countersunk.

[0077] Annular fin plates 45 are arranged around the cylindrical body 11. In Fig. 11, nine fin plates 45 are illustrated, but the number of fin plates 45 may be eight or less or ten or more. Four through holes are provided in the fin plate 45 at intervals of about 90 degrees. The fin plate 45 is made of a material with high thermal conductivity, such as aluminum, copper, or a high thermal conductivity grade resin mixed with a thermally conductive filler.

[0078] Cylindrical spacers 44 are arranged between the fin plates 45, between the uppermost fin plate 45 and the upper holding plate 431, between the upper holding plate 431 and the lid 42, between the lowermost fin plate 45 and the lower holding plate 432, and between the lower holding plate 432 and the upper surface of the main body 15.

[0079] Four fixing screws 46 pass through the lid 42, the upper holding plate 431, the lower holding plate 432, and the spacer 44. The fixing screws 46 are screwed into screw holes provided in the main body 15. With the above configuration, the fin plates 45 are fixed approximately parallel to the upper part of the main body 15 with a gap between them.

[0080] 13 is a half cross-sectional view and a bottom view of the cylinder 11, the upper holding plate 431, and the lower holding plate 432. The inner cylinder 111 is a stepped cylinder whose inner diameter increases in two steps from the bottom to the top. The inner wall of the lowest part forms a column hole 115 that is larger than the outer diameter of the column 14. The inner wall of the central part forms a holding wall 116 that is larger than the outer diameter of the vial 20. The inner diameter of the upper part is even larger than the inner diameter of the holding wall 116. The inner cylinder 111 has a thin brim-shaped part at the upper end.

[0081] It is desirable that the surface of the retaining wall 116 is smoothly finished. Although not shown in the drawings, it is desirable that the upper end portion of the retaining wall 116 is finished to a smoothly curved surface. As a result, it is possible to prevent scratches on the vial 20 caused by the retaining wall 116 and the vial 20 rubbing against each other during stirring.

[0082] The outer cylinder 112 is cylindrical with a uniform cross section. The outer diameter of the outer cylinder 112 is the same as the outer diameter of the brim-shaped portion of the inner cylinder 111. The inner diameter of the outer cylinder 112 is larger than the outer diameter of the inner cylinder 111, and there is a gap between the inner cylinder 111 and the outer cylinder 112. The outer cylinder 112 is provided with a sensor hole 117 that extends from the lower end face to near the center in the height direction. As shown in FIG. 11, a temperature sensor 51 is attached inside the sensor hole 117.

[0083] The protective tube 113 is cylindrical with a uniform cross section. The inner diameter of the protective tube 113 is larger than the outer diameter of the outer tube 112. The protective tube 113 is made of heat-resistant glass such as Pyrex (registered trademark). The protective tube 113 may also be made of resin such as acrylic resin or polycarbonate resin.

[0084] Heater 53 is disposed between inner cylinder 111 and outer cylinder 112. Heater 53 is formed by rolling a film heater of a resistance heating type, in which a thin conductor wire or a thin conductive film is sandwiched between insulating films such as polyimide films, into a cylindrical shape. Note that heater 53 may be of any type, such as a dielectric heating type or an induction heating type.

[0085] It is desirable that the heater 53, the inner cylinder 111, and the outer cylinder 112 are in close contact with each other. The inner cylinder 111 and the outer cylinder 112 are made of a material with high thermal conductivity, such as aluminum, copper, or a high thermal conductivity grade resin containing a thermally conductive filler, and it is desirable that they are heated quickly and uniformly by the heating of the heater 53.

[0086] Furthermore, it is desirable that inner cylinder 111 is made of a material that has a lower Mohs hardness than vial 20 and does not scratch vial 20. For example, if vial 20 is made of borosilicate glass, the Mohs hardness is about 5. The above-mentioned aluminum and copper have a Mohs hardness of about 2 to 3, which is lower than that of vial 20.

[0087] The upper portions of the four through holes provided at approximately 90 degree intervals in the upper holding plate 431 are deep countersunk. The lower portions of the four through holes provided at approximately 90 degree intervals in the lower holding plate 432 are deep countersunk. Each of the deep countersunk has an inner diameter slightly larger than the outer diameter of the spacer 44.

[0088] A central hole 433 having approximately the same inner diameter as the column hole 115 is provided in the center of the lower holding plate 432. As shown in the bottom view of Fig. 13, an intermediate hole 435 is provided between the central hole 433 and the four through holes. Note that only one intermediate hole 435 may be provided at a position corresponding to the sensor hole 117.

[0089] An annular upper rib 437 is provided on the lower surface of the upper holding plate 431. A lower rib 436 is provided on the upper surface of the lower holding plate 432. The upper rib 437 and the lower rib 436 have the same inner diameter and outer shape and face each other. The inner tube 111 and the outer tube 112 are held inside the upper rib 437. The protective tube 113 is held outside the upper rib 437.

[0090] Returning to Fig. 11, the explanation will be continued. The cable of the temperature sensor 51 is routed inside the main body 15 through the intermediate hole 435. The pillar 14 is inserted through the central hole 433 and the pillar hole 115. The tip of the pillar 14 is located inside the retaining wall 116.

[0091] 14 is an explanatory diagram illustrating the configuration of the shaker mixer 10 of the embodiment 3. The temperature sensor 51 and the heater 53 are connected to a temperature regulator 52. The temperature regulator 52 has a feedback control function for controlling the heater 53 so that the temperature measured by the temperature sensor 51 becomes a preset temperature.

[0092] A radiation detector 54 and a motor control unit 56 are disposed inside the main body 15. The radiation detector 54 is a sensor that detects gamma rays. The motor control unit 56 is connected to the motor 13. The radiation detector 54 and the motor control unit 56 are connected to a display unit 55.

[0093] The display 55 includes a display changeover switch 551. Depending on the switching state of the display changeover switch 551, the display 55 displays the radiation count or the rotation speed of the motor 13. The radiation count is expressed in units of CPS (counts per second). The rotation speed of the motor 13 is expressed in units of Hz. The display 55 may include two display sections: one that always displays the radiation count, and the other that always displays the rotation speed of the motor 13.

[0094] The motor control unit 56 has a speed adjustment dial 561, a speed changeover switch 562, a direction switch 563, and an ON / OFF switch 18. The ON / OFF switch 18 is a toggle switch used to switch the rotation of the motor 13 between ON and OFF. The direction switch 563 is a toggle switch that switches the rotation direction of the motor 13 between CW (ClockWise: clockwise) and CCW (Counter ClockWise: counterclockwise).

[0095] The speed changeover switch 562 is a toggle switch that changes the rotation speed of the motor 13 between a high-speed mode and a low-speed mode. The speed adjustment dial 561 is a dial that finely adjusts the rotation speed of the motor 13. For example, when the motor 13 is a DC motor, the speed changeover switch 562 is a dial for adjusting the resistance value of a variable resistor connected in series to the motor 13. The motor control unit 56 outputs to the display unit 55 the rotation speed of the motor 13, which is determined based on the value of the variable resistor or the DC voltage applied to the motor 13.

[0096] The range of rotational speeds of the motor 13 that can be adjusted by the speed adjustment dial 561 when the speed change switch 562 is set to high speed and the range of rotational speeds of the motor 13 that can be adjusted by the speed adjustment dial 561 when the speed change switch 562 is set to low speed may or may not overlap.

[0097] When they overlap, it is possible to provide a vibration mixer 10 in which the rotation speed of the motor 13 can be continuously adjusted over a wide range using the speed adjustment dial 561. When they do not overlap, it is possible to provide a vibration mixer 10 in which the rotation speed can be finely adjusted near the median value of each of the high and low rotation speeds.

[0098] An outline of a method for using the shaker / mixer 10 of this embodiment will be described below. In the following description, a case will be described as an example in which the target molecule has a chelate ring and the reaction is accelerated by heating.

[0099] As in the first embodiment, the user places the vial 20 on the columnar body 14. In the example shown in FIG. 11, the gap between the vial 20 and the inner cylinder 111 is smaller than that in the first embodiment, and the vial 20 can be tilted about 1 to 2 degrees inside the inner cylinder 111. The user punctures the rubber stopper of the vial 20 with the supply tube 31 and the vent needle 36. The user turns the ON / OFF switch 18 to the ON state and rotates the columnar body 14. The user adjusts the speed adjustment dial 561, the speed changeover switch 562, and the direction switch 563 so that the liquid inside the vial 20 is stirred without the vial 20 itself rotating much.

[0100] The user turns on the switch of the temperature regulator 52 (not shown). The temperature regulator 52 controls the heater 53 to heat the cylinder 11 to a predetermined temperature. Since the inner cylinder 111 and the outer cylinder 112 have high thermal conductivity, they are heated to a substantially uniform temperature by the heater 53. The temperature measured by the temperature sensor 51 is displayed on the temperature display unit 521. The vial 20 is also heated via the inner cylinder 111.

[0101] 10, the large number displayed on the upper side of the temperature display section 521 indicates the measured temperature. The small number displayed on the lower side of the temperature display section 521 indicates the target temperature. Both are in °C.

[0102] After the vial 20 has sufficiently warmed up, the user begins to supply the radionuclide from the generator 30 to the vial 20. In the vial 20, a reaction between the target molecule and the radionuclide proceeds, producing a drug for PET.

[0103] Since there is a space between outer cylinder 112 and protective cylinder 113, little heat is transferred from outer cylinder 112 to protective cylinder 113, and the temperature of protective cylinder 113 is less likely to rise than that of outer cylinder 112. If lower holding plate 432 and upper holding plate 431 are made of a material with low thermal conductivity, such as stainless steel or bubble-containing resin, the heat transferred to protective cylinder 113 can be further reduced.

[0104] The heat transferred from the protective tube 113 to the fin plate 45 through the air is dissipated into the air. That is, the protective tube 113 is cooled by the fin plate 45. The temperature of the fin plate 45 is even less likely to rise than that of the protective tube 113. The temperature of the lid 42 and the main body 15 also is less likely to rise because the heat transfer path from the heater 53 is narrow.

[0105] Therefore, the temperature rise in the parts that the user can easily touch is small, and it is possible to provide a shaking mixer 10 that is less likely to cause accidents such as burns.

[0106] According to the present embodiment, it is possible to provide a shaking mixer 10 that heats the vial 20. It is possible to provide a shaking mixer 10 that is unlikely to cause accidents such as a user being burned, even though the vial 20 is heated.

[0107] According to this embodiment, since the rotation speed of the motor 13 is displayed on the display 55, it is possible to provide a vibration mixer 10 that allows the user to easily adjust the rotation speed to an appropriate value. Since the amount of gamma rays detected by the radiation detector 54 is displayed on the display 55, it is possible to provide a vibration mixer 10 that allows the user to easily confirm that radioactive nuclides are being supplied from the generator 30.

[0108] For example, by making the protective cylinder 113 from a highly translucent material and appropriately selecting the colors of the outer cylinder 112 and the fin plate 45, it is possible to provide a shaking mixer 10 that has a high interior design appeal and is comfortable for the user to use.

[0109] The technical features (constitutive elements) described in each embodiment can be combined with each other, and by combining them, new technical features can be formed. The embodiments disclosed herein are illustrative in all respects and should not be considered as limiting. The scope of the present invention is defined by the claims, not by the above meaning, and is intended to include all modifications within the scope and meaning equivalent to the claims.

[0110] Independent claims and dependent claims described in the claims may be combined with each other in any combination, regardless of the reference format. Furthermore, the claims may be written in a format in which a claim references two or more other claims (multiple claim format), but this is not limited to this format. The claims may also be written in a format in which a multiple claim references at least one other claim (multiple multiple claim format). [Explanation of symbols]

[0111] 10. Shaking mixer 11 Cylinder 111 Inner cylinder 112 Outer cylinder 113 Protective tube 115 Column hole 116 Retaining Wall 117 Sensor hole 12 Pedestal 13 Motor 131 Motor shaft 14 Column 141 Shaft hole 142 Slope 143 Protrusion 144 Top 145 Cylinder 15 Main unit 18 ON / OFF switch 20 vials 30 Generator 31 Supply tube 36 Ventilating needle 40 Radiation Shielding 42 Lid 431 Upper holding plate 432 Lower holding plate 433 Central hole 435 Intermediate hole 436 Lower Rib 437 Upper Rib 44 Spacer 45 Fin plate 46 Fixing screw 51 Temperature Sensor 52 Temperature controller 521 Temperature display section 53 Heater 54 Radiation Detector 55 Display 551 Display switch 56 Motor control unit 561 Speed ​​adjustment dial 562 Speed ​​Switch 563 Directional Switch

Claims

1. A shaking mixer that shakes vials containing PET (Positron Emission Tomography) nuclides and labeling agents.

2. a base that holds the motor with the motor shaft facing upward; a resin column having a shaft hole into which the motor shaft is inserted at one end surface and a protrusion at the other end surface; a resin cylinder extending coaxially with the motor shaft from the base beyond the tip of the protrusion; The shaking mixer according to claim 1 .

3. The protrusion is disposed at a position away from the central axis of the shaft hole. The shaking mixer according to claim 2.

4. The vial is used in a state in which it is placed on the protrusion. The shaking mixer according to claim 2.

5. The vial is placed at an angle to the central axis of the cylinder. The shaking mixer according to claim 4.

6. a base that holds the motor with the motor shaft facing upward; a resin column having a shaft hole into which the motor shaft is inserted at one end surface and a protrusion at the other end surface; a cylindrical body extending coaxially with the motor shaft from the base to a position farther than the tip of the protrusion; a heater for heating the cylindrical body; The shaking mixer according to claim 1 .

7. The cylindrical body includes an inner cylinder and an outer cylinder, The heater is sandwiched between the inner cylinder and the outer cylinder. The shaking mixer according to claim 6.

8. A fin plate is provided surrounding the outer cylinder without contacting the outer cylinder. The shaking mixer according to claim 7.

9. A radiation shield is provided to cover the outer periphery of the cylindrical body. The shaking mixer according to any one of claims 2 to 8.

10. A tube extending from a generator that generates a nuclide for PET is connected to a vial containing a labeling agent; While the vial is being shaken by a shaking agitator, a nuclide for PET is supplied into the vial through the tube. Methods for processing nuclides for PET.

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