Radiopharmaceutical production apparatus and radiopharmaceutical production method

Abstract

To provide a radiopharmaceutical production apparatus and the like capable of reducing the generation amount of radioactive waste.SOLUTION: A radiopharmaceutical production apparatus 51 comprises: a cassette 20 which has a reagent supply port, a radionuclide supply port, a drug solution outlet, a reaction unit, a purification column, and flow paths respectively connecting the reagent supply port and the reaction unit, the radionuclide supply port and the reaction unit, the reaction unit and the purification column, and the purification column and the drug solution outlet; and a cassette mounting unit to which the cassette 20 is attachable and detachable.SELECTED DRAWING: Figure 3

Description

Technical Field

[0001] The present invention relates to a radioactive drug manufacturing apparatus and a radioactive drug manufacturing method.

Background Art

[0002] An automatic adjustment method for radioactive drugs has been proposed in which a disposable cassette containing a single dose of a drug is attached to an automatic synthesizer, and the drug and a radionuclide are reacted to produce a radioactive drug (Patent Document 1).

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] According to the automatic adjustment method of Patent Document 1, radioactive drugs used in medical institutions can be accurately manufactured each time they are used. However, since radionuclides remain in the cassette after use, they become radioactive waste. Therefore, the cost of treating the waste increases.

[0005] In one aspect, an object is to provide a radioactive drug manufacturing apparatus or the like that can reduce the amount of radioactive waste generated.

Means for Solving the Problems

[0006] The radioactive drug manufacturing apparatus includes a reagent supply port, a radionuclide supply port, a chemical solution outlet, a reaction unit, a purification column, and a cassette having flow paths connecting the reagent supply port and the reaction unit, the radionuclide supply port and the reaction unit, the reaction unit and the purification column, and the purification column and the chemical solution outlet, respectively, and a cassette attachment portion to which the cassette is detachably attached.

Effects of the Invention

[0007] On one hand, it is possible to provide a radioactive drug manufacturing apparatus or the like that can reduce the amount of radioactive waste generated.

Brief Description of the Drawings

[0008]

Figure 1

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Embodiments for Carrying Out the Invention

[0009] [Embodiment 1] FIG. 1 is an explanatory diagram for explaining the outline of the procedure for synthesizing a radiopharmaceutical. The radiopharmaceutical production system 50 of the present embodiment is used in a medical institution. The radiopharmaceutical production system 50 includes a radiopharmaceutical production apparatus 51 and an information processing apparatus 40. The radiopharmaceutical production apparatus 51 includes a cassette attachment portion and a cassette 20 that is detachably attached to the cassette attachment portion. The radiopharmaceutical production apparatus 51 is connected to the information processing apparatus 40. The information processing apparatus 40 controls the radiopharmaceutical production apparatus 51.

[0010] The cassette 20 incorporates a synthesis circuit according to the radiopharmaceutical to be produced. An RI solution containing a radioisotope (RI) for labeling the drug and a labeling precursor are supplied to the cassette 20. Note that although it is described as an RI solution, the radioisotope may be dispersed and mixed without being dissolved in the liquid.

[0011] In the synthesis circuit within the cassette 20, the labeling precursor and the radioisotope react. In the synthesis circuit within the cassette 20, purification is performed to remove impurities from the reaction product. Thus, the radiopharmaceutical is produced. After the production of the required amount of the radiopharmaceutical is completed, the synthesis circuit within the cassette 20 is automatically cleaned.

[0012] The radioactive agent is, for example, an agent for PET (Positron Emission Tomography), SPECT (Single Photon Emission Tomography), or a radiation therapy agent. Specific examples of the radioactive agent will be described later. When changing the radioactive agent to be manufactured, the cassette 20 is replaced. The cassette 20 removed from the radioactive agent manufacturing apparatus 51 is properly stored and reused when manufacturing the original radioactive agent.

[0013] After manufacturing a radioactive agent in a predetermined number of production runs or amount, or after the elapse of a predetermined period, the cassette 20 is returned from the medical institution to the manufacturer. The manufacturer performs maintenance on the cassette 20 and redelivers it to the medical institution. As described above, a radioactive agent manufacturing system 50 with a reduced amount of radioactive waste generation can be realized.

[0014] FIG. 2 is an explanatory diagram for explaining the configuration of the radioactive agent manufacturing system 50. The radioactive agent manufacturing system 50 includes a drug shielding container 72 and a server 58 in addition to the aforementioned radioactive agent manufacturing apparatus 51 and information processing apparatus 40. The radioactive agent manufacturing apparatus 51 includes a drive unit 30 in addition to the aforementioned cassette 20.

[0015] The cassette 20 includes a solenoid valve 10, a switching valve 11, a pump 13, a stirrer 14, a heater 15, a cooler 16, a purification column 17, a sensor 18, and a flow path 19. The flow path 19 connects other components to form a synthesis circuit. The switching valve 11, pump 13, stirrer 14, heater 15, cooler 16, purification column 17, and flow path 19 that make up the cassette are made of materials with high radiation resistance and corrosion resistance. The cassette 20 is not a single-use disposable item but is reused. Specific examples of the synthesis circuit will be described later.

[0016] The drive unit 30 includes a first control unit 31, a cassette I / F (Interface) 32, a first display unit 33, and a first communication unit 34. The first control unit 31 is, for example, one or more CPUs (Central Processing Units), GPUs (Graphics Processing Units), or multi-core CPUs, etc., and executes a program stored in a storage device (not shown). The first control unit 31 may be a logic circuit device such as an ASIC (Application Specific Integrated Circuit), FPCA (Field Programmable Gate Array), or CPLD (Complex Programmable Logic Device). The first control unit 31 may be an analog control circuit composed of, for example, a relay or the like. The first control unit 31 is connected to each hardware part constituting the drive unit 30 via a bus or wiring.

[0017] The cassette I / F 32 is an interface that connects the cassette 20 and the drive unit 30. Details of the cassette I / F 32 will be described later. The first display unit 33 is, for example, a liquid crystal display panel or an organic EL (Electro-Luminescence) panel, etc. Information regarding the radioactive drug being manufactured and information regarding the progress of the manufacturing process, etc. are displayed on the first display unit 33. The first communication unit 34 is an interface that performs communication between the drive unit 30 and the information processing device 40.

[0018] The drug shielding container 72 is, for example, a radiation shielding container made of tungsten, lead, or iron. Inside the drug shielding container 72, a drug container 723 (see FIG. 3) that houses the radioactive drug manufactured by the radioactive drug manufacturing apparatus 51 is held. The drug container 723 is, for example, a vial.

[0019] A second display unit 722 is arranged on the surface of the drug shielding container 72. The second display unit 722 is, for example, a liquid crystal display panel or an organic EL panel, etc. The name and lot number of the radioactive drug being manufactured, etc. are displayed on the second display unit 722.

[0020] The information processing apparatus 40 includes a second control unit 41, a main memory device 42, an auxiliary storage device 43, a second communication unit 442, a third communication unit 443, an input unit 45, an output unit 46, and a bus. The second control unit 41 is an arithmetic control device that executes the program of the present embodiment. One or more CPUs, GPUs, multi-core CPUs, etc. are used for the second control unit 41. The second control unit 41 is connected to each hardware part constituting the information processing apparatus 40 via a bus.

[0021] The main memory device 42 is a storage device such as SRAM (Static Random Access Memory), DRAM (Dynamic Random Access Memory), or flash memory. In the main memory device 42, information necessary during the processing performed by the second control unit 41 and the program being executed by the second control unit 41 are temporarily stored.

[0022] The auxiliary storage device 43 is a storage device such as SRAM, flash memory, hard disk, or magnetic tape. In the auxiliary storage device 43, the program to be executed by the second control unit 41 and various data necessary for the execution of the program are stored.

[0023] The second communication unit 442 is an interface that performs communication between the information processing apparatus 40 and a network or other devices. The second communication unit 442 performs communication based on, for example, the TCP / IP protocol. The third communication unit 443 is an interface that performs communication between the information processing apparatus 40 and the second display unit 722. The third communication unit 443 performs communication based on a wireless communication standard such as BLUETOOTH (registered trademark) or Wi-Fi (registered trademark).

[0024] The input unit 45 is an input device such as a keyboard, mouse, or microphone. The output unit 46 is an output device such as a liquid crystal display panel, organic EL panel, or speaker. The input unit 45 and the output unit 46 may be stacked to form a touch panel.

[0025] The information processing device 40 is an information device such as a general-purpose personal computer or a tablet. The information processing device 40 may be built into the radiopharmaceutical manufacturing device 51. When the information processing device 40 is built into the radiopharmaceutical manufacturing device 51, the second control unit 41 may also function as the first control unit 31.

[0026] The server 58 is a mainframe computer, a virtual machine operating on a mainframe computer, a plurality of personal computers performing distributed processing, or a cloud computing system. The server 58 may be an information device such as a general-purpose personal computer or a tablet.

[0027] FIG. 3 is a schematic diagram for explaining the configuration of the radiopharmaceutical manufacturing system 50. In FIG. 3, the illustration of the information processing device 40 and the server 58, and the illustration of the components of the cassette 20 are omitted. The radiopharmaceutical manufacturing system 50 includes, in addition to the aforementioned information processing device 40, server 58, radiopharmaceutical manufacturing device 51, and drug shielding container 72, a tray 74, reagent bottles 75, a cleaning solution bottle 76, an inert gas cylinder 785, an RI solution supply source 78, a waste liquid shielding container 727, and a charging stand 724.

[0028] The tray 74 is a dish-shaped container on which the reagent bottles 75 and the cleaning solution bottle 76 are placed. The reagent bottles 75 include a first reagent bottle 75A, a second reagent bottle 75B, a third reagent bottle 75C, and a fourth reagent bottle 75D. The first reagent bottle 75A contains the aforementioned labeled precursor solution. The second reagent bottle 75B contains Japanese Pharmacopoeia physiological saline. The third reagent bottle 75C contains absolute ethanol. The absolute ethanol may be Japanese Pharmacopoeia absolute ethanol or a highly biocompatible organic solvent. The fourth reagent bottle 75D contains Japanese Pharmacopoeia water for injection.

[0029] The cleaning solution bottle 76 includes a first cleaning solution bottle 76A, a second cleaning solution bottle 76B, and a third cleaning solution bottle 76C. The first cleaning solution bottle 76A contains cleaning water with a sterile endotoxin-free cleaning agent or sterile endotoxin-free pure water. The sterile endotoxin-free pure water is, for example, Japanese Pharmacopoeia water for injection. The second cleaning solution bottle 76B contains ethanol for disinfection according to the Japanese Pharmacopoeia. The third cleaning solution bottle 76C contains Japanese Pharmacopoeia water for injection.

[0030] Note that the number of reagent bottles 75 is not limited to four. Any number of reagent bottles 75 containing the reagents required for the production of the target radiopharmaceutical are prepared. Similarly, the number of cleaning solution bottles 76 is not limited to three. Any number of cleaning solution bottles 76 containing the cleaning solutions required for the production of the target radiopharmaceutical are prepared.

[0031] When the radiopharmaceutical manufacturing system 50 is used outside Japan, it is desirable to use medical-grade physiological saline, purified water, and disinfecting alcohol that are locally available instead of Japanese Pharmacopoeia physiological saline, Japanese Pharmacopoeia water for injection, and Japanese Pharmacopoeia ethanol for disinfection.

[0032] In the following description, the description of "Japanese Pharmacopoeia" is omitted for each of Japanese Pharmacopoeia physiological saline, Japanese Pharmacopoeia water for injection, and Japanese Pharmacopoeia ethanol for disinfection.

[0033] The inert gas cylinder 785 is a cylinder of argon gas or nitrogen gas. The RI solution supply source 78 includes at least one of a cyclotron 782 and an RI generator 781. The RI solution supply source 78 supplies an RI solution containing a radionuclide such as 68Ga (gallium 68), 18F (fluorine 18), or 99mTc (technetium 99m).

[0034] The reagent bottle 75, the cleaning solution bottle 76, the inert gas cylinder 785, and the RI solution supply source 78 are each connected to the cassette 20 via a tube and a sterilizing filter 789. The sterilizing filter 789 desirably has a pore size of 0.2 micrometers and is attached to the tip of the tube.

[0035] The waste liquid shielding container 727 is, for example, a radiation shielding container made of tungsten, lead, or iron. Inside the waste liquid shielding container 727, a waste liquid container 728 for containing the waste liquid discharged from the radioactive drug manufacturing apparatus 51 is held.

[0036] As shown in FIG. 3, a sterilizing filter 789 is also disposed at the base end of the tube extending from the cassette 20 to the drug shielding container 72. The sterilizing filter 789 at this position desirably has a pore size of 0.2 micrometers or a pore size of 0.22 micrometers. The charging stand 724 is disposed below the drug shielding container 72. The charging stand 724 is, for example, a wireless charger compliant with the Qi standard and supplies power to operate the second display unit 722.

[0037] In addition to the aforementioned first control unit 31, cassette I / F 32, first display unit 33, and first communication unit 34, the drive unit 30 includes a power button 356, a power indicator 357, a motor 351, a sensor drive unit 352, a heating / cooling drive unit 353, a sensor receiving unit 354, and a power outlet 355. The cassette I / F 32 includes a motor connection portion 321, a sensor connection portion 322, and a heating / cooling connection portion 323. The cassette I / F 32 is part of the cassette attachment portion.

[0038] The power button 356 is a switch for ON-OFF operation of the radioactive drug manufacturing apparatus 51. The power indicator 357 indicates the ON-OFF state of the power supply. The power outlet 355 is a so-called service outlet that supplies power from the drive unit 30 to the cassette 20. A power plug extending from the cassette 20 is inserted into the power outlet 355.

[0039] The motor 351 is a power source for switching the flow path of the switching valve 11. The drive unit 30 includes a number of motors 351 corresponding to the maximum number of switching valves 11 that the cassettes 20 to be used in combination have. A motor connection part 321 is attached to each motor 351. The motor connection part 321 is a coupling that couples to the switching valve 11.

[0040] The sensor connection part 322 is a rod with the detector part of the sensor 18 incorporated at its tip. The sensor 18 is, for example, a thermometer or a radiation detector. That is, by attaching the cassette 20 to the drive unit 30, various sensors 18 are arranged inside the cassette 20. The drive unit 30 includes a number of sensor connection parts 322 corresponding to the maximum number of sensors 18 to be arranged inside the cassettes 20 to be used in combination. A sensor drive part 352 that supplies a control signal or the like is connected to each sensor connection part 322.

[0041] That is, the cassette 20 is designed such that the motor connection part 321 and the sensor connection part 322 are fitted at the same position regardless of the type of radioactive drug to be manufactured.

[0042] The heating and cooling drive part 353 generates drive signals for the heater 15 and the cooler 16 respectively. The heating and cooling connection part 323 is a connector that connects the heating and cooling drive part 353 and the cassette 20. The sensor receiving part 354 receives the signals output from the output terminals of the respective sensors 18.

[0043] Figure 4 is a schematic diagram for explaining the configuration of the cassette 20. Using Figure 4, an example of the configuration of the synthesis circuit will be explained. In Figure 4, the solid lines connecting the components of the cassette 20 all indicate the flow path 19. In Figure 4, the illustration of the reference signs of the flow path 19 is omitted.

[0044] There are a total of 15 solenoid valves 10 from solenoid valve 10A to solenoid valve 10O. There are a total of 8 switching valves 11 from the first switching valve 111 to the eighth switching valve 118. There are a total of 4 pumps 13 from the first pump 131 to the fourth pump 134. There are a total of 2 stirrers 14, namely the first stirrer 141 and the second stirrer 142. The sensor 18 is a thermocouple and is arranged to measure the temperature of the heater 15.

[0045] For the convenience of creating the schematic diagram, the arrangement order of the 9 switching valves 11 from solenoid valve 10A to solenoid valve 10I is different between FIG. 3 and FIG. 4. The connection destinations of each solenoid valve 10 will be described later.

[0046] The first switching valve 111 and the second switching valve 112 have 6 ports from A to F. The third switching valve 113 has 8 ports from A to H. The fourth switching valve 114 to the eighth switching valve 118 each have 3 ports from A to C. In the following description, for example, the A port of the first switching valve 111 may be described as port 111A, and the B port of the second switching valve 112 may be described as port 112B.

[0047] For the first switching valve 111 and the second switching valve 112, the ports from A to E are the inflow ports, and the F port is the outflow port. For the third switching valve 113, the ports from A to G are the inflow ports, and the H port is the outflow port. For the fourth switching valve 114 to the eighth switching valve 118, the A port is the inflow port, and the B and C ports are the outflow ports.

[0048] Table 1 shows the connection destinations of each solenoid valve 10.

[0049]

Table 1

[0050] The first electromagnetic valve 10A connected to the inert gas cylinder 785 is an example of the inert gas supply port in this embodiment. The second electromagnetic valve 10B connected to the RI solution supply source 78 is an example of the radionuclide supply port in this embodiment. The third electromagnetic valve 10C to the fifth electromagnetic valve 10E connected to the cleaning solution bottle 76 are examples of the cleaning solution supply ports in this embodiment.

[0051] The third electromagnetic valve 10C connected to the first cleaning solution bottle 76A containing cleaning water with a sterile endotoxin-free cleaning agent or sterile endotoxin-free pure water is an example of the cleaning water supply port in this embodiment. The fourth electromagnetic valve 10D connected to the second cleaning solution bottle 76B containing ethanol for Japanese Pharmacopoeia disinfection is an example of the ethanol supply port in this embodiment. The fifth electromagnetic valve 10E connected to the third cleaning solution bottle 76C containing water for injection is an example of the water supply port in this embodiment.

[0052] The sixth electromagnetic valve 10F to the ninth electromagnetic valve 10I connected to the reagent bottle 75 are examples of the reagent supply ports in this embodiment. The sixth electromagnetic valve 10F connected to the first reagent bottle 75A containing the labeling precursor solution is an example of the precursor supply port in this embodiment. The seventh electromagnetic valve 10G connected to the second reagent bottle 75B containing physiological saline is an example of the physiological saline supply port in this embodiment. The eighth electromagnetic valve 10H connected to the third reagent bottle 75C containing absolute ethanol is an example of the supply port for ethanol and the like in this embodiment.

[0053] The tenth electromagnetic valve 10J connected to the drug container 723 is an example of the chemical liquid outlet in this embodiment. The eleventh electromagnetic valve 10K to the fifteenth electromagnetic valve 10O connected to the waste liquid container 728 are examples of the waste liquid outlets in this embodiment.

[0054] As is clear from Table 1, among the two outflow ports provided by the fourth switching valve 114 to the eighth switching valve 118, the C outflow port is connected to the waste liquid container 728 via the electromagnetic valve 10. In the following description, the description of the C outflow port of the fourth switching valve 114 to the eighth switching valve 118 will be omitted.

[0055] Port 111F, which is the outflow port of the first switching valve 111, is connected to the inflow port of the first pump 131 via the fourth switching valve 114. Port 112F, which is the outflow port of the second switching valve 112, is connected to the inflow port of the second pump 132 via the fifth switching valve 115. The outflow ports of the first pump 131 and the second pump 132 are connected to the inflow port of the first stirrer 141.

[0056] The outflow port of the first stirrer 141 is connected to the inflow port of the fourth pump 134 via the heater 15, the cooler 16, and the seventh switching valve 117. The flow path 19 is formed, for example, in a coil shape inside the heater 15 and the cooler 16, and the fluid flowing inside is maintained at a predetermined temperature for a predetermined time.

[0057] Port 113H, which is the outflow port of the third switching valve 113, is connected to the inflow port of the third pump 133 via the sixth switching valve 116. The outflow ports of the third pump 133 and the fourth pump 134 are connected to the inflow port of the second stirrer 142.

[0058] The outflow port of the second stirrer 142 is connected to the purification column 17. The outflow port of the purification column 17 is connected to the chemical agent container 723 via the eighth switching valve 118 and the Jth solenoid valve 10J.

[0059] Using FIGS. 2 to 4, an overview of the manufacturing process of the radiopharmaceutical will be described. The user attaches the cassette 20 corresponding to the radiopharmaceutical to be manufactured to the radiopharmaceutical manufacturing apparatus 51. When attaching and detaching the cassette 20, the user operates the input unit 45 to cause the second control unit 41 to execute the "synthesis circuit detachment program". The second control unit 41 closes all the solenoid valves 10 based on the "synthesis circuit detachment program".

[0060] The user checks that the appropriate reagents and cleaning solutions according to the radiopharmaceutical to be manufactured are contained in the reagent bottle 75 and the cleaning solution bottle 76, and replaces the reagent bottle 75 and the cleaning solution bottle 76 as necessary. Even if the contents of the reagent bottle 75 and the cleaning solution bottle 76 are insufficient, the user replaces the reagent bottle 75 and the cleaning solution bottle 76.

[0061] When the user replaces the reagent bottle 75 and the cleaning solution bottle 76, it is desirable to also replace the tubes connecting the respective bottles to the cassette 20 and the sterilization filters 789 attached to the ends of the tubes with new ones.

[0062] The user checks that the appropriate RI solution according to the radiopharmaceutical to be manufactured is being supplied from the RI solution supply source 78, and replaces the RI solution supply source 78 as necessary. The user checks the internal pressure of the inert gas cylinder 785 and replaces the inert gas cylinder 785 as necessary.

[0063] The user houses the dummy drug container 723 in the drug shielding container 72 and connects the drug container 723 to the Jth electromagnetic valve 10J. The user checks that the available capacity of the waste liquid container 728 is sufficient and replaces the waste liquid container 728 as necessary.

[0064] After the above preparations are complete, the user operates the information processing device 40 to start the drug synthesis program described later. It is desirable that the drug synthesis program be set so that only registered users can use it through user authentication using, for example, password authentication or biometric authentication.

[0065] The user operates the input unit 45 to input the current date and time, the name of the radiopharmaceutical to be synthesized, the drug lot number, the lot numbers of the respective reagents contained in the reagent bottle 75, etc. If the above-mentioned user authentication is not performed, the user also inputs their name, ID number, etc. The current date and time may be automatically acquired via the network. Then the user operates the input unit 45 to instruct the start of synthesis.

[0066] The second control unit 41 identifies the type of the attached cassette 20 based on, for example, a barcode attached to the cassette 20 or an IC tag attached to the cassette 20. The second control unit 41 determines whether the correct cassette 20 corresponding to the name of the radiopharmaceutical input by the user is attached.

[0067] If the correct cassette 20 is not attached, the second control unit 41 outputs from the output unit 46 that the cassette 20 needs to be replaced and waits for the user's operation. Similarly, the second control unit 41 may determine whether the correct reagent bottle 75, cleaning solution bottle 76, RI solution supply source 78, and inert gas cylinder 785 are attached, and output the necessity of replacement or replenishment as necessary.

[0068] After the correct cassette 20 etc. are attached, the second control unit 41 controls the radiopharmaceutical manufacturing apparatus 51 to perform automatic cleaning of the radiopharmaceutical manufacturing apparatus 51. Specifically, the second control unit 41 opens the electromagnetic valves 10 from the second electromagnetic valve 10B to the tenth electromagnetic valve 10O, and closes the other electromagnetic valves 10.

[0069] The second control unit 41 opens the ports of all the switching valves 11. The second control unit 41 sequentially opens the electromagnetic valves 10 one by one, and sends the cleaning solution in the first cleaning solution bottle 76A, inert gas, ethanol for disinfection in the second reagent bottle 75B, inert gas, water for injection in the third reagent bottle 75C, and inert gas into the cassette 20 in this order.

[0070] The time for opening each electromagnetic valve 10 is set based on a cleaning validation test in accordance with the pharmaceutical GMP (Good Manufacturing Practice) standard. Therefore, it is ensured that the sterility, residual solvents, and impurities of the radiopharmaceutical manufactured using the radiopharmaceutical manufacturing system 50 are below the allowable range.

[0071] After the automatic cleaning is completed, the second control unit 41 outputs from the output unit 46 that preparations are complete for replacing the dummy chemical agent container 723 with a new chemical agent container 723. The user accommodates the new chemical agent container 723 in the chemical agent shielding container 72 and aseptically connects the chemical agent container 723 and the J-th electromagnetic valve 10J. At this time, it is desirable for the user to also replace the sterilization filter 789 disposed between the J-th electromagnetic valve 10J and the chemical agent container 723 with a new one.

[0072] The second control unit 41 mixes the RI solution supplied from the RI solution supply source 78 via the B-th electromagnetic valve 10B and the first switching valve 111 with the labeling precursor supplied from the A-th reagent bottle 75A via the F-th electromagnetic valve 10F and the second switching valve 112 using the first stirrer 141. The mixed solution reacts in the process of passing through the heater 15, and a radioactive drug is generated. The flow path 19 passing through the heater 15 is an example of the reaction part of the present embodiment.

[0073] As shown in FIG. 4, the cassette 20 includes a flow path 19 that connects the F-th electromagnetic valve 10F, which is one of the reagent supply ports, and the reaction part. The cassette 20 includes a flow path 19 that connects the B-th electromagnetic valve 10B, which is the radioactive nuclide supply port, and the reaction part. The cassette 20 includes a flow path 19 that connects the reaction part and the purification column 17. The cassette 20 includes a flow path that connects the purification column 17 and the J-th electromagnetic valve 10J, which is the chemical solution outlet.

[0074] The cassette 20 includes a flow path 19 that connects the C-th electromagnetic valve 10C, which is the cleaning liquid supply port, the E-th electromagnetic valve 10E, and the reaction part. The cassette 20 includes a flow path 19 that connects the A-th electromagnetic valve 10A, which is the inert gas supply port, and the reaction part. The cassette 20 includes a flow path 19 that connects the purification column 17 and the K-th electromagnetic valve 10K, which is one of the waste liquid outlets.

[0075] The second control unit 41 sends the liquid containing the radioactive drug cooled to room temperature after passing through the cooler 16 into the purification column 17. Inside the purification column 17, a functional resin that adsorbs and holds the radioactive drug is filled. The functional resin filled in the purification column 17 is, for example, a hydrophobic resin or an ion exchange resin.

[0076] The second control unit 41 sends physiological saline into the purification column 17 from the second reagent bottle 75B via the seventh electromagnetic valve 10G, the third switching valve 113, the sixth switching valve 116, the third pump 133, and the second stirrer 142, and discharges the impurities remaining in the purification column 17 into the waste liquid container 728 via the eighth switching valve 118 and the eleventh electromagnetic valve 10K.

[0077] The second control unit 41 sends absolute ethanol into the purification column 17 from the third reagent bottle 75C via the eighth electromagnetic valve 10H, the third switching valve 113, the sixth switching valve 116, the third pump 133, and the second stirrer 142. The radioactive agent adsorbed and held in the purification column 17 elutes into the absolute ethanol. The second control unit 41 collects the ethanol in which the radioactive agent has eluted into the agent container 723 via the eighth switching valve 118 and the tenth electromagnetic valve 10J.

[0078] The second control unit 41 sends physiological saline into the purification column 17 from the second reagent bottle 75B via the seventh electromagnetic valve 10G, the third switching valve 113, the sixth switching valve 116, the third pump 133, and the second stirrer 142, and collects the radioactive agent remaining in the purification column 17 into the agent container 723 via the eighth switching valve 118 and the tenth electromagnetic valve 10J.

[0079] As described above, the purified radioactive agent is collected into the agent container 723 without waste. After producing a predetermined amount of radioactive agent, the second control unit 41 records a production record sheet compliant with pharmaceutical GMP standards in the auxiliary storage device 43. The second control unit 41 uploads the production record sheet to the server 58 each time production is performed or periodically.

[0080] FIG. 5 is a flowchart for explaining the processing flow of the agent synthesis program. Note that since the user authentication process before program startup has been conventionally used, the description of the flowchart is omitted.

[0081] The second control unit 41 receives inputs from the user such as the current date and time, the name of the radiopharmaceutical to be synthesized, the drug lot number, and the lot numbers of the respective reagents contained in the reagent bottles 75 (step S501). The second control unit 41 refers to a database (not shown) stored in the auxiliary storage device 43 or the server 58 to obtain the synthesis conditions of the radiopharmaceutical (step S502).

[0082] The synthesis conditions obtained in step S502 include, for example, the model number of the cassette 20 to be used, the types of reagents that should be contained in the respective reagent bottles 75, the timing and amount of reagent input from the respective reagent bottles 75 to the cassette 20, the driving conditions of the pump 13, the temperatures of the heater 15 and the cooler 16, and other information.

[0083] The second control unit 41 determines whether the correct cassette 20 corresponding to the radiopharmaceutical to be manufactured is attached to the radiopharmaceutical manufacturing apparatus 51 (step S503). If it is determined that it is not attached (NO in step S503), the second control unit 41 outputs to the output unit 46 information for the user to attach the correct cassette 20 to the radiopharmaceutical manufacturing apparatus 51, such as the model number of the correct cassette 20 and the replacement procedure of the cassette 20 (step S504). The second control unit 41 waits until the correct cassette 20 is attached (step S505).

[0084] If it is determined that it is attached (YES in step S503), the second control unit 41 determines whether the radiopharmaceutical manufacturing apparatus 51 is in a usable state (step S511). Specifically, the second control unit 41 determines whether the reagent bottles 75 containing the correct reagents corresponding to the radiopharmaceutical to be manufactured and the RI solution supply source 78 are connected to the cassette 20, whether the amount of reagent in the reagent bottles 75 is sufficient, whether the amount of cleaning liquid in the cleaning liquid bottle 76 is sufficient, whether the internal pressure of the inert gas cylinder 785 is sufficient, and the like.

[0085] When it is determined that the radiopharmaceutical manufacturing apparatus 51 is not in a usable state (NO in step S511), the second control unit 41 outputs, to the output unit 46, information for correcting the radiopharmaceutical manufacturing apparatus 51 to a usable state, such as, for example, the type of reagent bottle 75 to be replaced and the method for replacing the reagent bottle 75 (step S512).

[0086] The second control unit 41 waits until the user corrects the radiopharmaceutical manufacturing apparatus 51 to a usable state (step S513). When it is determined that the radiopharmaceutical manufacturing apparatus 51 is in a usable state (YES in step S511), after the end of step S513 or after the end of step S505, the second control unit 41 performs automatic cleaning of the radiopharmaceutical manufacturing apparatus 51 (step S514).

[0087] The second control unit 41 waits until the user removes the dummy reagent container 723 from the cassette 20 and attaches a new reagent container 723 to the cassette 20 (step S515). The second control unit 41 displays information regarding the radiopharmaceutical to be manufactured on the first display unit 33 and the second display unit 722 (step S516).

[0088] The second control unit 41 manufactures the radiopharmaceutical (step S517). Specifically, the second control unit 41 operates the electromagnetic valve 10, the switching valve 11, the pump 13, the heater 15, the cooler 16, etc. based on the synthesis conditions acquired in step S502. Information regarding the radiopharmaceutical being manufactured continues to be displayed on the first display unit 33 and the second display unit 722.

[0089] After the manufacture of the specified amount of the radiopharmaceutical is completed, the second control unit 41 notifies the user of the completion of the manufacture (step S518). The notification of the completion of the manufacture is made, for example, by display on the first display unit 33. The second control unit 41 may transmit a notification of the completion of the manufacture to a smartphone or the like held by the user via, for example, SMS (Short Message Service). The user can perform work in another room or the like while waiting for the manufacture of the radiopharmaceutical.

[0090] The user who has received the end notification takes out the drug container 723 from the drug shielding container 72 and connects a dummy drug container to the cassette 20. The second control unit 41 performs automatic cleaning of the radioactive drug manufacturing apparatus 51 (step S519). The procedure for automatic cleaning is the same as that in step S514. Thereafter, the second control unit 41 ends the process.

[0091] According to the present embodiment, it is possible to provide a radioactive drug manufacturing apparatus 51 that can reduce the amount of radioactive waste generated. By replacing the cassette 20 and the RI solution supply source 78, it is possible to provide a radioactive drug manufacturing apparatus 51 that can manufacture various types of radioactive drugs.

[0092] According to the present embodiment, since the cassette 20 can be used multiple times, the manufacturing cost of radioactive drugs can be reduced. Since the cassette 20 that has been used multiple times can be used again after being maintained by the manufacturer, the manufacturing cost of radioactive drugs can be further reduced.

[0093] According to the present embodiment, it is possible to provide a radioactive drug manufacturing apparatus 51 that can manufacture radioactive drugs of a quality compliant with pharmaceutical GMP within a medical institution. Since it is not necessary to deliver radioactive drugs from a distant manufacturer, a medical institution can promptly perform inspections and treatments using radioactive drugs when necessary.

[0094] [Embodiment 2] This embodiment relates to a cassette 20 that uses radioactive metal ions as radionuclides. Descriptions of parts common to Embodiment 1 are omitted. Radionuclides that become radioactive metal ions are, for example, 64Cu (copper 64), 67Cu (copper 67), 67Ga (gallium 67), 68Ga (gallium 68), 69Zr (zirconium 69), 90Y (yttrium 90), 99mTc (technetium 99m: metastable nuclear isomer of technetium), 111In (indium 111), 153Sm (samarium 153), 177Lu (lutetium 177), 186Re (rhenium 186), 188Re (rhenium 188), 212Pb (lead 212), 223Ra (radium 223), and 225Ac (actinium 225).

[0095] Radioactive metal ions bind to the labeling precursor by a chelation reaction. Therefore, cassette 20 is provided with a synthesis circuit suitable for the chelation reaction. Table 2 shows examples of radiopharmaceuticals that can be generated using radioactive metal ions.

[0096] [Table 2]

[0097] FIG. 6 is a schematic diagram for explaining the configuration of cassette 20 of Embodiment 2. The synthesis circuit of cassette 20 shown in FIG. 6 is similar to the synthesis circuit of cassette 20 described with reference to FIG. 4, but is different in that there is no branch in flow path 19, instead, the number of solenoid valves 10 is large, and a switching valve 11 is arranged between pump 13 and stirrer 14.

[0098] The configuration of the synthesis circuit of Embodiment 2 will be described with reference to FIG. 6. In FIG. 6, solid lines connecting the components of cassette 20 all indicate flow path 19. In FIG. 6, the reference signs of flow path 19 are omitted.

[0099] There are a total of 30 solenoid valves 10 from solenoid valve 10A to solenoid valve 10Z and from solenoid valve 10a to solenoid valve 10d. There are a total of 8 switching valves 11 from switching valve 111 to switching valve 118. There are a total of 4 pumps 13 from pump 131 to pump 134. There are a total of 2 stirrers 14, namely stirrer 141 and stirrer 142. The illustration and description of sensor 18 are omitted.

[0100] The first switching valve 111, the second switching valve 112, and the fourth switching valve 114 have seven ports from A to G. The third switching valve 113 has nine ports from A to I. The fifth switching valve 115 to the eighth switching valve 118 each have three ports from A to C.

[0101] The first switching valve 111 and the second switching valve 112 have ports A to F as the inflow ports and port G as the outflow port. The third switching valve 113 has ports A to H as the inflow ports and port I as the outflow port. The outflow ports of the first switching valve 111, the second switching valve 112, and the third switching valve 113 are always in the open state.

[0102] The fourth switching valve 114 has ports A and B as the outflow ports and ports C to G as the inflow ports. The fifth to eighth switching valves 115 to 118 have port A as the inflow port and ports B and C as the outflow ports. The fifth to eighth switching valves 115 to 118 are normally in a state where port A communicates with port B and port C is closed.

[0103] Table 3 shows the connection destinations of the electromagnetic valve 10 provided in the cassette 20 of the second embodiment. In this embodiment, the connection destinations outside the cassette 20 are indicated by the names of reagents or cleaning liquids to be introduced into the cassette 20. Reagents, cleaning liquids, and gases with the same name may be supplied to the cassette 20 from one reagent bottle 75, cleaning liquid bottle 76, or inert gas cylinder 785, or may be supplied to the cassette 20 from individual reagent bottles 75, cleaning liquid bottles 76, or inert gas cylinders 785.

[0104] For example, water for injection is used for both reagent and cleaning liquid purposes. Both reagent water for injection and cleaning liquid water for injection may be supplied from one bottle. That is, the reagent bottle 75 that supplies water for injection may also serve as the cleaning liquid bottle 76.

[0105]

Table 3

[0106] As is clear from Table 3, among the two outflow ports provided by the fifth switching valve 115 to the eighth switching valve 118, the C outflow port is connected to the drain via the solenoid valve 10. In the following description, the description of the C outflow port of the fifth switching valve 115 to the eighth switching valve 118 will be omitted.

[0107] Port 111G, which is the outflow port of the first switching valve 111, is connected to the inflow port of the first pump 131. The outflow port of the first pump 131 is connected to the inflow port of the first stirrer 141 via the fifth switching valve 115.

[0108] Port 112G, which is the outflow port of the second switching valve 112, is connected to the inflow port of the second pump 132. The outflow port of the second pump 132 is connected to the inflow port of the first stirrer 141 via the sixth switching valve 116. The outflow port of the first stirrer 141 is connected to the inflow port of the fourth pump 134 via the heater 15 and the cooler 16. The outflow port of the fourth pump 134 is connected to the inflow port of the second stirrer 142 via the eighth switching valve 118.

[0109] Port 113I, which is the outflow port of the third switching valve 113, is connected to the inflow port of the third pump 133. The outflow port of the third pump 133 is connected to the inflow port of the second stirrer 142 via the seventh switching valve 117.

[0110] The outflow port of the second stirrer 142 is connected to the purification column 17. The outflow port of the purification column 17 is connected to port 114G of the fourth switching valve 114. Port 114A, which is the outflow port of the fourth switching valve 114, is connected to the waste liquid container 728 via the U solenoid valve 10U. Port 114B, which is the outflow port of the fourth switching valve 114, is connected to the chemical agent container 723 via the V solenoid valve 10V and the sterilization filter 789.

[0111] FIG. 7 is an explanatory diagram for explaining the outline of the radioactive drug synthesis procedure according to Embodiment 2. Using FIG. 7, the outline of the radioactive drug synthesis procedure when using a radioactive metal ion as the radionuclide will be described.

[0112] First, the RI solution and the labeling precursor solution are mixed. The mixed solution is heated to a temperature of 50°C to 100°C by the heater 15. The heating time is about 5 minutes to 30 minutes. The specific temperature and time vary depending on the radioactive drug to be produced. During heating, the labeling precursor and the radionuclide are bound by a chelation reaction to generate a radioactive drug.

[0113] The liquid mixed with the generated radioactive drug is cooled to room temperature in the cooler 16. The radioactive drug is adsorbed onto the purification column 17. By flowing a liquid that does not elute the radioactive drug through the purification column 17, impurities are removed from the purification column 17. Next, by flowing a drug that elutes the radioactive drug through the purification column 17, the radioactive drug is eluted from the purification column 17. The radioactive drug eluted from the purification column 17 is taken out. Thus, the production of the radioactive drug is completed.

[0114] Note that the reagents used for impurity removal and elution of the radioactive drug vary depending on the radioactive drug to be produced.

[0115] The first A solenoid valve 10A, the first G solenoid valve 10G, the first M solenoid valve 10M, and the first Q solenoid valve 10Q to which an inert gas is supplied are examples of the inert gas supply ports of the present embodiment. The first B solenoid valve 10B to which the RI solution is supplied is an example of the radionuclide supply port of the present embodiment.

[0116] The solenoid valve 10 that supplies various reagents used in the synthesis of radiopharmaceuticals is an example of a reagent supply port in this embodiment. The solenoid valve 10 that supplies various cleaning liquids used for cleaning the cassette 20 is an example of a cleaning liquid supply port in this embodiment. Note that the cassette 20 may be configured such that the liquid supplied from one solenoid valve 10 is used as both a reagent and a cleaning liquid depending on the supply timing. When using the cassette 20 configured in this way, one solenoid valve 10 serves as both a reagent supply port and a cleaning liquid supply port.

[0117] The solenoid valves 10D, 10J, and 10R that supply water for injection are examples of water supply ports in this embodiment. The solenoid valve 10H that supplies a labeling precursor solution is an example of a precursor supply port in this embodiment. The solenoid valves 10C and 10I that supply physiological saline used in the synthesis of radiopharmaceuticals are examples of physiological saline supply ports in this embodiment.

[0118] The solenoid valves 10F, 10L, and 10T that supply ethanol for disinfection and the solenoid valve 10P that supplies absolute ethanol are examples of ethanol supply ports in this embodiment.

[0119] The solenoid valve 10V from which a radiopharmaceutical is derived is an example of a chemical liquid outlet in this embodiment. The solenoid valve 10V from which waste liquid is derived is an example of a waste liquid outlet in this embodiment.

[0120] Figures 8 to 14 are explanatory diagrams for explaining the radiopharmaceutical synthesis procedure of Embodiment 2. In Figures 8 to 14, among the schematic diagrams described using Figure 6, the flow path 19 in the open state is shown by a thick line. Figure 8 shows the start-up of the radiopharmaceutical manufacturing apparatus 51. The second control unit 41 opens the solenoid valves 10A, 10G, 10M, and 10U and closes the other solenoid valves 10. Further, the second control unit 41 opens the ports 111A, 112A, 113A, and 114A and closes the other inflow ports of these switching valves 11.

[0121] The flow paths 19 indicated by thick lines each communicate with the outside of the cassette 20. However, since the first pump 131, the second pump 132, and the third pump 133 are not operating, the inflow of the inert gas into the cassette 20 stops in a state where the pressure in the flow path 19 and the pressure of the inert gas cylinder 785 are in equilibrium. The second control unit 41 turns on the heater 15.

[0122] Continuing the explanation with reference to FIG. 9. The second control unit 41 closes the first solenoid valve 10A, the seventh solenoid valve 10G, and the thirteenth solenoid valve 10M, and opens the second solenoid valve 10B, the eighth solenoid valve 10H, and the fourteenth solenoid valve 10N. The second control unit 41 closes the port A of the first switching valve 111, the second switching valve 112, and the third switching valve 113, and opens the port B. Even at this stage, since the first pump 131, the second pump 132, and the third pump 133 are not operating, the liquid flowing into the flow path 19 is minimal.

[0123] Continuing the explanation with reference to FIG. 10. The second control unit 41 operates the four pumps 13. The RI solution flowing in from the solenoid valve 10 and the labeled precursor solution flowing in from the eighth solenoid valve 10H are mixed by the first stirrer 141. The mixed solution reacts in the process of passing through the heater 15 heated to a predetermined temperature over a predetermined time, and a radiopharmaceutical is generated.

[0124] The liquid containing the radiopharmaceutical cooled to room temperature by the cooler 16 and the precursor dissolution solvent supplied from the fourteenth solenoid valve 10N are mixed by the second stirrer 142 and then sent to the purification column 17. The radiopharmaceutical is adsorbed by the purification column 17, and impurities such as unreacted precursors flow out to the waste liquid container 728 through the twenty-first solenoid valve 10U.

[0125] Continue the description with reference to FIG. 11. The second control unit 41 closes the second B solenoid valve 10B, the second H solenoid valve 10H, and the second N solenoid valve 10N, and opens the second C solenoid valve 10C, the second I solenoid valve 10I, and the second O solenoid valve 10O. The second control unit 41 closes the B ports of the first switching valve 111, the second switching valve 112, and the third switching valve 113, and opens the C ports. The second control unit 41 stops the operation of the heater 15.

[0126] Physiological saline flows into the flow paths 19 indicated by thick lines respectively, and flushes out the RI solution, the labeled precursor solution, the radioactive agent, etc. remaining in the flow paths 19. The radioactive agent is adsorbed by the purification column 17, and the rest flows out to the waste liquid container 728.

[0127] Continue the description with reference to FIG. 12. The second control unit 41 closes the second C solenoid valve 10C, the second I solenoid valve 10I, and the second O solenoid valve 10O, and opens the second P solenoid valve 10P and the second V solenoid valve 10V. The second control unit 41 closes the port 113B and the port 114A, and opens the port 113D and the port 114B. The second control unit 41 stops the first pump 131, the second pump 132, and the fourth pump 134.

[0128] Absolute ethanol flows from the second P solenoid valve 10P into the purification column 17 via the third switching valve 113, the third pump 133, the seventh switching valve 117, and the second stirrer 142. The radioactive agent adsorbed by the purification column 17 dissolves in the absolute ethanol and flows out of the purification column 17. The radioactive agent flows out to the agent container 723 via the fourth switching valve 114 and the second V solenoid valve 10V.

[0129] Continue the description with reference to FIG. 13. The second control unit 41 closes the second P solenoid valve 10P and opens the second O solenoid valve 10O. The second control unit 41 closes the port 113D and opens the port 113C.

[0130] From the Oth electromagnetic valve 10O, physiological saline flows into the purification column 17 via the third switching valve 113, the third pump 133, the seventh switching valve 117, and the second stirrer 142. The radioactive agent remaining in the purification column 17 and the flow path 19 flows out into the agent container 723 via the fourth switching valve 114 and the Vth electromagnetic valve 10V.

[0131] Continuing the explanation using FIG. 14. The second control unit 41 closes the Oth electromagnetic valve 10O and opens the Qth electromagnetic valve 10Q. The second control unit 41 closes the port 113C and opens the port 113E.

[0132] The flow path 19 indicated by the thick line is filled with the inert gas flowing in from the Qth electromagnetic valve 10Q, and the remaining liquid flows out into the agent container 723. Thus, the radioactive agent generated by the reaction between the RI solution and the radioactive precursor solution is stored in the agent container 723 without waste. Thus, the production of the radioactive agent is completed.

[0133] FIG. 15 is an explanatory diagram for explaining the automatic cleaning procedure of the second embodiment. In FIG. 15, among the schematic diagrams described using FIG. 6, the flow path 19 in the open state is indicated by a thick line. FIG. 15 shows the first step of the automatic cleaning. The second control unit 41 opens the Dth electromagnetic valve 10D, the Jth electromagnetic valve 10J, the Rth electromagnetic valve 10R, and the Uth electromagnetic valve 10U, and closes the other electromagnetic valves 10. The second control unit 41 opens the ports 111D, 112D, 113F, and 114A, and closes the other inflow ports of these switching valves 11. The second control unit 41 operates the pumps 13 from the first pump 131 to the fourth pump 134.

[0134] Physiological saline flows in from the Dth electromagnetic valve 10D, the Jth electromagnetic valve 10J, and the Rth electromagnetic valve 10R respectively, and flushes the flow path 19 indicated by the thick line. The second control unit 41 operates the electromagnetic valves 10 and the switching valves 11 to flush the flow path 19 in the cassette 20 in the order of inert gas, bipolar solvent, inert gas, ethanol for disinfection, inert gas, water for injection, and inert gas.

[0135] According to this embodiment, a radiopharmaceutical manufacturing system 50 that manufactures a radiopharmaceutical using a radioactive metal ion as a radionuclide can be provided. Since the cassette 20 itself does not contain reagents and radionuclides, by appropriately selecting the reagent bottle 75 and the RI solution supply source 78, a cassette 20 that can be used for manufacturing various radiopharmaceuticals can be provided.

[0136] [Embodiment 3] This embodiment relates to a cassette 20 that uses a radioactive halogen element as a radionuclide. Descriptions of parts common to Embodiment 1 are omitted. Examples of radioactive halogen elements are 77Br (bromine 77), 123I (iodine 123), 125I (iodine 125), 131I (iodine 131), and 211At (astatine 211).

[0137] The radioactive halogen element binds to the labeling precursor by a chemical reaction. Therefore, the cassette 20 is provided with a synthesis circuit suitable for chemical reactions. Table 4 shows examples of radiopharmaceuticals that can be produced using radioactive halogen elements.

[0138]

Table 4

[0139] FIG. 16 is a schematic diagram for explaining the configuration of the cassette 20 of Embodiment 3. Using FIG. 16, the configuration of the synthesis circuit of Embodiment 2 will be described. In FIG. 16, solid lines connecting the components of the cassette 20 all indicate flow paths 19. In FIG. 16, the illustration of the reference signs of the flow paths 19 is omitted.

[0140] The solenoid valves 10 are a total of 40 from solenoid valve 10A to solenoid valve 10Z and from solenoid valve 10a to solenoid valve 10n. The switching valves 11 are a total of 11 from the first switching valve 111 to the eleventh switching valve 121. The pumps 13 are a total of 6 from the first pump 131 to the sixth pump 136. The stirrers 14 are a total of 3 from the first stirrer 141 to the third stirrer 143. The illustration and description of the sensor 18 are omitted.

[0141] The first switching valve 111, the second switching valve 112, and the fourth switching valve 114 have seven ports from A to G. The third switching valve 113 and the eleventh switching valve 121 have nine ports from A to I.

[0142] The fifth switching valve 115 to the tenth switching valve 120 each have three ports from A to C. In FIG. 16, the port symbols for the fifth switching valve 115 to the tenth switching valve 120 are omitted. In all cases, the port on the left side in the figure is port A, the port on the right side is port B, and the port on the lower side is port C.

[0143] For the first switching valve 111 and the second switching valve 112, the ports from A to F are the inflow ports, and the port G is the outflow port. For the third switching valve 113 and the eleventh switching valve 121, the ports from A to H are the inflow ports, and the port I is the outflow port. The outflow ports of the first switching valve 111, the second switching valve 112, the third switching valve 113, and the eleventh switching valve 121 are always in an open state.

[0144] For the fourth switching valve 114, the ports A and B are the outflow ports, and the ports from C to G are the inflow ports. For the fifth switching valve 115 to the tenth switching valve 120, the port A is the inflow port, and the ports B and C are the outflow ports. For the fifth switching valve 115 to the tenth switching valve 120, normally, port A and port B are in communication, and port C is in a closed state.

[0145] Table 5 shows the connection destinations of the electromagnetic valves 10 provided in the cassette 20 of Embodiment 2. The same parts as in Table 3 are shown in italics. In this embodiment, the connection destinations outside the cassette 20 are indicated by the names of reagents or cleaning liquids to be introduced into the cassette 20. Reagents, cleaning liquids, and gases with the same name may be supplied to the cassette 20 from one reagent bottle 75, cleaning liquid bottle 76, or inert gas cylinder 785, or may be supplied to the cassette 20 from individual reagent bottles 75, cleaning liquid bottles 76, or inert gas cylinders 785.

[0146]

Table 5

[0147] As is clear from Table 5, among the two outflow ports provided in the fifth switching valve 115 to the tenth switching valve 120, the C outflow port is connected to the drain via the electromagnetic valve 10. In the following description, the description of the C outflow port of the fifth switching valve 115 to the tenth switching valve 120 will be omitted.

[0148] The connection from the first A electromagnetic valve 10A to the inflow port of the purification column 17 through the first T electromagnetic valve 10T is the same as that of the cassette 20 of Embodiment 2 described with reference to FIG. 6, so the description thereof will be omitted. The outflow port of the purification column 17 is connected to the inflow port of the fifth pump 135. The outflow port of the fifth pump 135 is connected to the inflow port of the third stirrer 143.

[0149] Port 121I, which is the outflow port of the eleventh switching valve 121, is connected to the inflow port of the sixth pump 136. The outflow port of the sixth pump 136 is connected to the inflow port of the third stirrer 143 via the tenth switching valve 120.

[0150] The outflow port of the third stirrer 143 is connected to port 114G of the fourth switching valve 114. Port 114A, which is the outflow port of the fourth switching valve 114, is connected to the waste liquid container 728 via the U-th electromagnetic valve 10U. Port 114B, which is the outflow port of the fourth switching valve 114, is connected to the chemical agent container 723 via the V-th electromagnetic valve 10V and the sterilization filter 789.

[0151] FIG. 17 is an explanatory diagram for explaining the outline of the radioactive drug synthesis procedure of Embodiment 3. Using FIG. 17, the outline of the radioactive drug synthesis procedure when a radioactive halogen element is used as the radionuclide will be explained.

[0152] First, the RI solution and the pre-labeling precursor solution are mixed. The mixture is heated to a predetermined temperature by the heater 15 and maintained at that temperature for a predetermined time. During the heating, the pre-labeling precursor and the radionuclide are combined by a chemical reaction to generate a radioactive intermediate.

[0153] The liquid mixed with the generated radioactive intermediate is cooled to room temperature in the cooler 16. The radioactive intermediate is adsorbed onto the purification column 17. A deprotection reagent is injected into the purification column 17. Then, by leaving it for a predetermined time, a radioactive drug is generated by a chemical reaction. The flow path 19 passing through the heater 15 and the purification column 17 are examples of the reaction section of the present embodiment.

[0154] By flowing injection water into the purification column 17, the radioactive drug flows out from the purification column 17. A buffer solution is mixed with the outflowing radioactive drug to neutralize it. The neutralized radioactive drug is taken out. Thus, the radioactive drug is completed.

[0155] As shown in FIG. 6, the cassette 20 includes a flow path 19 that connects the B-th electromagnetic valve 10B, which is a radionuclide supply port, and the reaction section. The cassette 20 includes a flow path that connects the purification column 17 and the V-th electromagnetic valve 10V, which is a chemical liquid outlet.

[0156] The cassette 20 includes a flow path 19 that connects the first electromagnetic valve 10A and the seventh electromagnetic valve 10G, which are inert gas supply ports, to the reaction section, respectively. The cassette 20 includes a flow path 19 that connects the purification column 17 and the fifth electromagnetic valve 10V, which is a waste liquid outlet port.

[0157] According to the present embodiment, a radiopharmaceutical manufacturing system 50 for manufacturing a radiopharmaceutical using a radioactive halogen element as a radionuclide can be provided. Since the cassette 20 itself does not contain reagents and radionuclides, by appropriately selecting the reagent bottle 75 and the RI solution supply source 78, a cassette 20 that can be used for manufacturing various radiopharmaceuticals can be provided.

[0158] [Embodiment 4] This embodiment relates to a form in which the information processing apparatus 40 is realized by operating in combination with a general-purpose computer 90 and a program 97. For parts common to Embodiment 1, the description is omitted.

[0159] FIG. 18 is an explanatory diagram for explaining the configuration of the radiopharmaceutical manufacturing system 50 according to Embodiment 4. The computer 90 includes a reading unit 49 in addition to the aforementioned second control unit 41, main storage device 42, auxiliary storage device 43, second communication unit 442, third communication unit 443, input unit 45, output unit 46, and bus.

[0160] The program 97 is recorded on a portable recording medium 96. The second control unit 41 reads the program 97 via the reading unit 49 and stores it in the auxiliary storage device 43. Further, the second control unit 41 may read the program 97 stored in a semiconductor memory 98 such as a flash memory mounted in the computer 90. Furthermore, the second control unit 41 may download the program 97 from another server computer (not shown) connected via the second communication unit 442 and a network and store it in the auxiliary storage device 43.

[0161] The program 97 is installed as a control program for the computer 90, loaded into the main memory device 42, and executed. As described above, the information processing apparatus 40 described in the first embodiment is realized. The program 97 of the present embodiment is an example of a program product.

[0162] A computer program can be deployed to be executed on a single computer, or placed at one site, or distributed across multiple sites and executed on multiple computers interconnected by a communication network.

[0163] The technical features (constituent elements) described in each embodiment can be combined with each other, and new technical features can be formed by such combination. The embodiments disclosed this time should be considered as illustrative in all respects and not restrictive. The scope of the present invention is shown not by the above meaning, but by the claims, and is intended to include all modifications within the meaning and scope equivalent to the claims.

[0164] The independent claims and dependent claims described in the claims can be combined with each other in any combination regardless of the citation form. Further, the claims use a form (multi-claim form) of describing a claim that cites two or more other claims, but are not limited thereto. A form of describing a multi-claim (multi-multi-claim) that cites at least one multi-claim may be used.

Description of Reference Numerals

[0165] 10 Electromagnetic valve 11 Switching valve 111 First switching valve 112 Second switching valve 113 Third switching valve 114 Fourth switching valve 115 Fifth switching valve 116 Sixth switching valve 117th switching valve 118th switching valve 119th switching valve 120th switching valve 121st switching valve 13 Pump 131st pump 132nd pump 133rd pump 134th pump 135th pump 136th pump 14 Stirrer 141st stirrer 142nd stirrer 143rd stirrer 15 Heater 16 Cooler 17 Purification column 18 Sensor 19 Flow path 20 Cassette 30 Drive unit 31 First control unit 32 Cassette I / F 321 Motor connection part 322 Sensor connection part 323 Heating / cooling connection part 33 First display unit 34 First communication unit 351 Motor 352 Sensor drive unit 353 Heating / cooling drive unit 354 Sensor receiving unit 355 Power outlet 356 Power button 357 Power indicator 40 Information processing device 41 Second control unit 42 Main memory device 43 Auxiliary memory device 442 Second communication unit 443 Third communication unit 45 Input unit 46 Output unit 49 Reading unit 50 Radioactive drug manufacturing system 51 Radioactive drug manufacturing apparatus 58 Server 72 Drug shielding container 722 Second display unit 723 Drug container 724 Charging stand 727 Waste liquid shielding container 728 Waste liquid container 74 Tray 75 Reagent bottle 76 Cleaning liquid bottle 78 RI solution supply source 781 RI generator 782 Cyclotron 785 Inert gas cylinder 789 Sterilizing filter 90 Computer 96 Portable recording medium 97 Program 98 Semiconductor memory

Claims

1. A cassette having a reagent supply port, a radionuclide supply port, a chemical solution outlet, a reaction section, a purification column, and flow paths connecting the reagent supply port and the reaction section, the radionuclide supply port and the reaction section, the reaction section and the purification column, and the purification column and the chemical solution outlet, and a cassette mounting section for removably mounting the cassette. A radioactive drug manufacturing apparatus.

2. The reaction section chemically reacts a labeled precursor solution supplied from the reagent supply port with a radionuclide supplied from the radionuclide supply port. The radioactive drug manufacturing apparatus according to claim 1.

3. The reaction section chelates a labeled precursor solution supplied from the reagent supply port with a radionuclide supplied from the radionuclide supply port. The radioactive drug manufacturing apparatus according to claim 1.

4. The reagent supply port includes a precursor supply port to which a labeled precursor solution is supplied, a physiological saline supply port to which physiological saline is supplied, and an ethanol or highly biocompatible organic solvent supply port to which ethanol or the like is supplied. The radioactive drug manufacturing apparatus according to claim 1.

5. The cassette includes a cleaning solution supply port, an inert gas supply port, and a waste liquid outlet, the flow path includes portions connecting the cleaning solution supply port and the reaction section, the inert gas supply port and the reaction section, and the purification column and the waste liquid outlet, the cleaning solution supply port includes a cleaning water supply port to which water or water containing a cleaning agent is supplied, an ethanol supply port to which ethanol is supplied, and a water supply port to which sterile endotoxin-free water is supplied. The radioactive drug manufacturing apparatus according to claim 1.

6. It includes a control section for controlling valves and pumps attached to the flow path. The radioactive drug manufacturing apparatus according to claim 1.

7. It includes a display section for displaying information on the radioactive drug being manufactured. The radioactive drug manufacturing apparatus according to any one of claims 1 to 6.

8. Receives information on a radioactive drug to be manufactured using a radioactive drug manufacturing apparatus, determines whether the radioactive drug can be manufactured using a cassette removably attached to the radioactive drug manufacturing apparatus, when it is determined that manufacturing is not possible, outputs information on the cassette used for manufacturing the radioactive drug, when it is determined that manufacturing is possible, causes the radioactive drug manufacturing apparatus to manufacture the radioactive drug. A radioactive drug manufacturing method in which a computer executes the process.

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