JP4361537B2 - Maintenance method of radiochemical solution synthesizer and radiochemical solution synthesizer with cleaning function - Google Patents

Description

  The present invention relates to a maintenance method for a radiochemical solution synthesizer and a radiochemical solution synthesizer with a cleaning function.

A nuclear medicine diagnostic method for diagnosing diseases and the like by administering a radiopharmaceutical solution containing a compound labeled with a radionuclide (RI) into the body and imaging the state in which the labeled compound is collected at a specific location in the body with a dedicated device. Has been developed. In this diagnostic method, ¹⁸ F-FDG (fluorodeoxyglucose) or the like labeled with a relatively short-lived radionuclide (for example, ¹⁸ F has a half-life of 110 minutes as a positron emitting nuclide) Used.

  An apparatus for synthesizing such a radiochemical solution is disclosed in Patent Document 1, for example. This synthesizer includes a fixed module and a disposable module. In this synthesizing apparatus, when one synthesis is completed, the disposable module is replaced with a new one to prepare for the next synthesis.

Here, the synthesis of the radiopharmaceutical was performed only once a day in the radiation shield, and the radiation shield was opened the next day after the residual radioactivity was sufficiently reduced, and the disposable module was replaced.
Special table 2004-515330 gazette

  In recent years, such a synthesizer is desired to be able to synthesize a plurality of times a day. However, if the radiation shield is opened immediately after the synthesis of the radiopharmaceutical and the disposable module is replaced, the level of residual radioactivity is high, and there is a risk that the exposure amount of the operator will be high.

  The present invention has been made in view of the above-described circumstances, and maintains a low exposure amount of the radioactive chemical liquid handler while maintaining a radioactive chemical liquid synthesizing apparatus that enables efficient synthesis of the radioactive chemical liquid, and An object is to provide a radiochemical solution synthesizer with a cleaning function.

  As a result of earnest research to achieve the above-mentioned object, the inventors have a high level of residual radioactivity in the reaction container among the disposable modules, and the residual radioactivity in the entire disposable module is thoroughly washed. The present inventors have found that the level of can be sufficiently reduced, and have completed the present invention. The present invention is based on such knowledge.

  That is, a maintenance method for a radiochemical solution synthesizer according to the present invention is a maintenance method for a radiochemical solution synthesizer comprising a removal module including a reaction vessel for synthesizing a radiochemical solution, and a fixed module in which the removal module is installed. It is. In this method, after the synthesized radiochemical solution is discharged from the reaction vessel, the cleaning solution is introduced into the reaction vessel while the module is removed from the fixed module, and the reaction vessel is washed with the introduced washing solution. After the cleaning liquid is discharged from, the removal module is replaced.

  In this method, the removal module is replaced after the reaction vessel is cleaned and the cleaning liquid is discharged. Therefore, the removal module can be replaced with a low level of residual radioactivity, and the exposure amount of the operator is kept low. be able to. And since it can move to the next synthesis | combination without waiting for the level of residual radioactivity fully falling, a radioactive chemical | medical solution can be synthesize | combined efficiently.

  When cleaning the inside of the reaction vessel with the cleaning liquid, it is preferable to bubble the cleaning liquid with an inert gas. In this way, the cleaning effect of the radioactive chemical remaining in the reaction container can be enhanced.

  When washing the inside of the reaction vessel with the washing liquid, it is preferable to boil the washing liquid. In this way, the cleaning effect of the radioactive chemical remaining in the reaction container can be enhanced.

  The removal module preferably includes a water introduction path for introducing water used for discharging the radioactive chemical liquid from the reaction vessel into the reaction vessel. And it is preferable to introduce | transduce a washing | cleaning liquid in a reaction container through a water introduction path. In this way, the water introduction path can be used both for the introduction of water and the introduction of the cleaning liquid, and the complication of the configuration of the synthesizer can be avoided.

  A radiochemical solution synthesizing apparatus with a cleaning function according to the present invention includes a fixed module in which a removal module including a reaction vessel that synthesizes a radiochemical solution is installed, a cleaning solution storage unit that stores a cleaning solution that cleans the inside of the reaction vessel, and a cleaning solution And a cleaning liquid introduction path for discharging the cleaning liquid from the reaction container.

  ADVANTAGE OF THE INVENTION According to this invention, the maintenance method of the radioactive chemical | medical-solution synthesis | combination apparatus which enables efficient synthesis | combination of a radioactive chemical | medical solution, and the radioactive chemical | medical-solution synthesis | combination apparatus with a washing | cleaning function which enable the efficient synthesis | combination of a radioactive chemical | medical solution are possible, maintaining the exposure amount of the handler of a radioactive chemical solution low. be able to.

Hereinafter, embodiments of the present invention will be described with reference to the drawings. In the following description, the same reference numerals are used for the same elements, and duplicate descriptions are omitted. Moreover, this embodiment demonstrates the case where ¹⁸ F-FDG (fluorodeoxyglucose) is synthesize | combined as a radioactive chemical | medical solution.

  FIG. 1 is a perspective view showing a configuration of a radioactive chemical solution synthesizing apparatus with a cleaning function according to the present embodiment. FIG. 2 is a front view showing a configuration of a removal module provided in the synthesizing apparatus of FIG. As shown in FIGS. 1 and 2, the synthesis apparatus 10 includes a removal module 12 and a fixed module 14.

  The removal module 12 includes a target recovery vial 15, a reaction vial (reaction vessel) 16, a plurality of lines L1-L15 for flowing a fluid, and a plate 18 that positions and supports the plurality of lines L1-L15. is doing. The plurality of lines L1-L15 are formed from a silicone tube or the like.

The target recovery vial 15 irradiates H ₂ ¹⁸ O with high energy protons accelerated by a cyclotron (not shown), and recovers target water containing ¹⁸ F ions (radioactive fluorine) generated by the nuclear reaction. This target recovery vial 15 has a capacity of about 7 cc and a bottom that is V-shaped, and it is easy to discharge the recovered target water to the subsequent stage. The target recovery vial 15 includes a recovery line L1 for recovering target water, a vacuum line L2 for evacuating the inside of the vial 15, a gas introduction line L3 for introducing N ₂ gas as an inert gas, and a recovery Is connected to a discharge line L4 for discharging the target water. The base end of the discharge line L4 extends to the lowest point of the V-shaped bottom.

The end of this discharge line L4 is connected to the middle of an introduction line L5 for introducing a potassium carbonate (K ₂ CO ₃ ) solution and a cryptofix 222 (K222) solution. The end portion of the introduction line L5 is connected to one end of the anion exchange resin cartridge 20 for capturing ¹⁸ F ions. The other end of the anion exchange resin cartridge 20 is connected to a recovery line L6 for recovering the target water after capturing ¹⁸ F ions. Since the anion exchange resin cartridge 20 is not included in the removal module 12, it is indicated by a broken line.

The reaction vial 16 is a vial for reacting raw materials to synthesize a radiopharmaceutical solution. The reaction vial 16 has a capacity of about 7 cc and a flat bottom, and has improved reactivity. The reaction vial 16 includes a first multipurpose line L7 for introducing N ₂ gas as an inert gas and the like, and a second multipurpose line L8 that branches from the first multipurpose line L7 and whose end portion extends to the flat bottom of the reaction vial 16. And a vacuum line L9 for evacuating the inside of the vial 16 is connected.

  The first multipurpose line L7 and the recovery line L6 are connected by a connection line L10. An introduction line L11 for introducing acetonitrile is connected to the connection line L10. Acetonitrile introduced through the introduction line L11 is used for flowing the solution in the line.

  An introduction line L12 for introducing mannose triflate dissolved in acetonitrile is connected on the first multipurpose line L7 between the branch point of the second multipurpose line L8 and the connection point of the connection line L10. Has been.

  Further, a drainage line L15 for discharging the synthesized radiopharmaceutical is branched from the middle of the second multipurpose line L8. In the middle of the drainage line L15, a water introduction line (water introduction path) L13 for introducing water used for discharging the radioactive drug solution from the reaction vial 16 into the reaction vial 16 is connected. . Near the base end of the water introduction line L13, a water storage part 22 for storing about 5 cc of water to be introduced is connected. Further, a cleaning liquid storage unit 24 that stores about 5 cc of cleaning liquid for cleaning the reaction vial 16 is connected to the upstream side of the water storage unit 22 near the base end of the water introduction line L13. An introduction line L14 for introducing a sodium hydroxide solution for hydrolysis is connected to the water introduction line L13.

  The plate 18 is formed in a rectangular shape from, for example, a resin material such as polypropylene, and supports the plurality of lines L1-L15 described above by positioning the plurality of claw portions 26 at predetermined positions. A back plate 13 is provided at a predetermined position of the plate 18 for crushing the lines L1-L15 with a piston 28 described later.

  The fixed module 14 is a member having a substantially cubic shape and has a main body portion 32 and a door portion 34. An attachment portion 36 for attaching the plate 18 of the removal module 12 is provided on the front surface of the main body portion 32. An accommodation hole 38 for accommodating the target recovery vial 15 is provided on the upper surface of the main body 32. Furthermore, an accommodation hole 40 for accommodating the reaction vial 16 is provided on the upper surface of the step portion 32 a of the main body portion 32. Around the accommodation hole 40, a heater (not shown) for heating the reaction vial 16 is provided.

  The door part 34 is provided so that it can be opened and closed by 90 degrees in the direction of arrow A through a hinge provided on the side surface of the step part 32 a of the main body part 32. The door portion 34 can be opened and closed with respect to the main body portion 32 by rotating the knob 42 and engaging the hook 44 with the engagement hole 46 of the main body portion 32 and releasing the engagement. A plurality of pistons 28 are provided at predetermined positions inside the door portion 34. The plurality of pistons 28 move back and forth by the force of air. Air is supplied to each piston 28 via an air tube 48 extending from the main body portion 32. Thus, the piston 28 can be moved back and forth, and the line L1-L15 can be crushed or returned to the substantially circular back plate 13 to function as an on-off valve. For convenience of explanation, reference numerals 13-1 to 13-13 are attached to the back plate 13 of FIG. 2, and the on-off valves 13-1 to 13-13 configured with the piston 28 are distinguished.

  In such a radiochemical solution synthesizer 10 with a cleaning function, a purification column 50 for purifying the radiochemical solution is connected to the drain line L15. A product supply line L16 for supplying a purified chemical solution extends from the purification column 50 toward a product vial (not shown). The purification column 50 is covered with a shielding material that shields radiation.

  Next, the maintenance method of the above-described radiochemical solution synthesizing apparatus 10 with a cleaning function will be described including the method for synthesizing the radiochemical solution.

When synthesizing ¹⁸ F-FDG as a radiochemical solution, first, H ₂ ¹⁸ O is irradiated with high-energy protons accelerated by a cyclotron (not shown), and about 2 cc containing ¹⁸ F ions (radioactive fluorine) generated by a nuclear reaction. The target water is recovered in the target recovery vial 15 through the recovery line L1. At this time, it is preferable to evacuate through the vacuum line L2 because the target water can be easily introduced into the target recovery vial 15 and confined easily.

Next, N ₂ gas is introduced into the target recovery vial 15 through the gas introduction line L3, and the entire amount of target water is discharged through the discharge line L4. At this time, by closing the on-off valves 13-1 and 13-4 and opening the on-off valves 13-2 and 13-3, the target water is passed through the anion exchange resin cartridge 20 to capture ¹⁸ F ions. Then, the remaining target water is recovered through the recovery line L6.

Next, the potassium carbonate solution is passed through the anion exchange resin cartridge 20 through the introduction line L5, and the ¹⁸ F ions are eluted and introduced into the reaction vial 16. At the same time, a cryptofix solution is introduced into the reaction vial 16. At this time, the on-off valves 13-2, 13-3, 13-5, 13-6, 13-7 are closed and the on-off valves 13-1, 13-4, 13-12 are opened. In this state, about 0.9 cc of raw material is accommodated in the reaction vial 16.

Next, the reaction vial 16 is evacuated through the vacuum line L9 and the reaction vial 16 is heated by a heater (not shown) to evaporate and dry the ¹⁸ F ion, potassium carbonate solution, and cryptofix solution. Remove.

  Next, mannose triflate dissolved in acetonitrile is introduced into the reaction vial 16 through the introduction line L12 and the first multipurpose line L7. At this time, the on-off valves 13-4, 13-5, and 13-7 are closed, and the on-off valve 13-12 is opened. Then, in a state where the reaction vial 16 is sealed, it is heated for 5 minutes at a set temperature of 100 ° C. by a heater (not shown). Thereby, fluorination of mannose triflate is performed. In this state, the reaction vial 16 contains about 1.3 cc of raw material.

  Next, the reaction vial 16 is evacuated through the vacuum line L9, and the reaction vial 16 is heated by a heater (not shown) to boil the liquid inside, thereby removing acetonitrile that is harmful to the human body. The set temperature of the heater (not shown) at this time is about 80 ° C.

Next, about 4 cc of sodium hydroxide is introduced into the reaction vial 16 through the introduction line L14. At this time, the on-off valves 13-8, 13-10, and 13-11 are closed, and the on-off valves 13-9 and 13-13 are opened. And the preset temperature of the heater which is not illustrated shall be 100 degreeC, and it heats in a sealing state and performs hydrolysis. At this time, the on-off valves 13-7, 13-9, 13-10, 13-11 are closed and the on-off valves 13-8, 13-13 are opened, and the reaction vials are passed through the first multipurpose line L7 and the second multipurpose line L8. It is preferable that N ₂ gas is introduced into 16 and bubbled. If it does in this way, an internal liquid will be stirred and a hydrolysis will be accelerated | stimulated. In this way, ¹⁸ F-FDG is synthesized in the reaction vial 16.

Then, N ₂ gas is introduced into the reaction vial 16 through the first multipurpose line L7, and ¹⁸ F-FDG is discharged through the second multipurpose line L8 and the drainage line L15. At this time, the on-off valves 13-4, 13-5, 13-6, 13-8, 13-9, 13-10 are closed, and the on-off valves 13-7, 13-11, 13-12, 13-13 are opened. Keep it. Then, impurities are removed through the purification column 50, and pure ¹⁸ F-FDG is taken out and supplied to the product vial through the product supply line L16.

Thereafter, about 5 cc of water is introduced from the water reservoir 22 into the reaction vial 16 through the water introduction line L13. At this time, the on-off valves 13-8, 13-9, and 13-11 are closed, and the on-off valves 13-10 and 13-13 are opened. Then, N ₂ gas is introduced into the reaction vial 16 through the first multipurpose line L7, and with the water introduced with ¹⁸ F-FDG remaining in the reaction vial 16 through the second multipurpose line L8 and the drainage line L15. Discharge. At this time, the on-off valves 13-4, 13-5, 13-6, 13-8, 13-9, 13-10 are closed, and the on-off valves 13-7, 13-11, 13-12, 13-13 are opened. Keep it. Then, impurities are removed through the purification column 50, and pure ¹⁸ F-FDG is taken out and supplied to the product vial through the product supply line L16.

Synthesis of ¹⁸ F-FDG by the above-described radioactive chemical synthesizing apparatus 10 with a cleaning function is performed in a radiation shield (hot cell) (not shown). Then, after one synthesis is completed, the removal module 12 is replaced.

  When replacing the removal module 12, the radiation shield (not shown) is not opened. Therefore, the removal module 12 is left installed in the fixed module 14, and about 5 cc of the cleaning liquid is stored in the reaction vial 16 through the water introduction line L13. Is introduced. At this time, the on-off valves 13-8, 13-9, and 13-11 are closed, and the on-off valves 13-10 and 13-13 are opened. As the cleaning solution, water, acetonitrile, an organic solvent, or the like can be used.

Next, the on-off valves 13-7, 13-9, 13-10, 13-11 are closed and the on-off valves 13-8, 13-13 are opened, and the reaction vials are passed through the first multipurpose line L7 and the second multipurpose line L8. N ₂ gas is introduced into 16 and the cleaning liquid is bubbled. Further, the reaction vial 16 is heated by a heater (not shown) to boil the cleaning liquid. Thereby, ¹⁸ F-FDG stuck in the reaction vial 16 is dissolved, and the inside of the reaction vial 16 is washed. This reduces the radioactivity level in the reaction vial 16 to 5 mSv / year or less.

Then, N ₂ gas is introduced into the reaction vial 16 through the first multipurpose line L7, and the cleaning liquid is discharged from the reaction vial 16 through the second multipurpose line L8 and the drainage line L15.

  Thereafter, the radiation shield (not shown) is opened, the door 34 of the radiochemical solution synthesizing apparatus 10 with the cleaning function is opened, the used removal module 12 is removed from the main body 32 of the fixed module 14 and replaced with a new one.

  As described above in detail, in the maintenance method of the radioactive chemical synthesizing apparatus 10 according to the present embodiment, the removal module 12 is replaced after the inside of the reaction vial 16 is washed and the washing liquid is discharged, so that the level of residual radioactivity is low. In this state, the removal module 12 can be replaced, and the exposure amount of the handler can be kept low. Moreover, although a part of radioactive substance remains in the purification column 50, since the purification column 50 is shielded by the shielding material, the exposure amount of the handler can be kept lower. And since it can move to the next synthesis | combination without waiting for the level of residual radioactivity fully falling, a radioactive chemical | medical solution can be synthesize | combined efficiently. According to the calculation of the present inventor, under the condition that the synthesis is performed twice a day for 300 days, the reaction vial 16 is washed and the purification column 50 is shielded, and no washing and the purification column 50 are not shielded. In this case, the annual exposure amount of the operator can be reduced from 1/6 to about 1/7.

In addition, since the cleaning liquid is bubbled with N ₂ gas when the inside of the reaction vial 16 is cleaned with the cleaning liquid, the cleaning effect of the radioactive chemical remaining in the reaction vial 16 can be enhanced.

  Further, since the cleaning liquid is boiled when the reaction vial 16 is cleaned with the cleaning liquid, the cleaning effect of the radioactive chemical remaining in the reaction vial 16 can be further enhanced.

  Further, by introducing the washing liquid into the reaction vial 16 through the water introduction line L13, the water introduction line L13 can be used both for the introduction of water and the introduction of the washing liquid, and the configuration of the radioactive chemical synthesizing apparatus 10 is complicated. Can be avoided.

  The present invention is not limited to the above-described embodiment, and various modifications can be made. For example, in the above embodiment, sodium hydroxide is introduced into the reaction vial 16 for hydrolysis, but hydrochloric acid may be introduced.

Moreover, although the said embodiment demonstrated the case where ¹⁸ F-FDG was synthesize | combined as a radioactive chemical | medical solution, you may synthesize | combine another radioactive chemical | medical solution.

It is a perspective view which shows the structure of the radioactive chemical solution synthesizer with a washing function which concerns on this embodiment. It is a front view which shows the structure of the removal module with which the synthesizing | combining apparatus of FIG. 1 is provided.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 10 ... Radiochemical solution synthesizer with a cleaning function, 12 ... Removal module, 14 ... Fixed module, 15 ... Target collection vial, 16 ... Reaction vial, 18 ... Plate, 24 ... Cleaning liquid storage part, 32 ... Main part, 34 ... Door Part, L13 ... water introduction line, L15 ... drainage line, L1-L16 ... line.

Claims (5)

A removal method including a reaction vessel for synthesizing a radiochemical solution, and a fixed module on which the removal module is installed, and a maintenance method for a radiochemical solution synthesizer comprising:
After discharging the synthesized radiochemical solution from the reaction vessel, the cleaning solution is introduced into the reaction vessel while the removal module is installed in the fixed module.
The inside of the reaction vessel is washed with the introduced washing liquid,
After removing the cleaning liquid from the reaction vessel, the removal module is replaced.
The maintenance method of the radioactive chemical | medical solution synthesizer characterized by the above-mentioned.   The method for maintaining a radioactive chemical solution synthesizer according to claim 1, wherein when the inside of the reaction vessel is cleaned with the cleaning liquid, the cleaning liquid is bubbled with an inert gas.   The method for maintaining a radioactive chemical solution synthesizer according to claim 1 or 2, wherein the cleaning solution is boiled when the inside of the reaction vessel is cleaned with the cleaning solution. The removal module includes a water introduction path for introducing water used for discharging the radioactive chemical liquid from the reaction vessel into the reaction vessel,
The maintenance method for a radioactive chemical solution synthesizer according to any one of claims 1 to 3, wherein the cleaning liquid is introduced into the reaction vessel through the water introduction path. A fixed module on which a removal module including a reaction vessel for synthesizing a radiochemical solution is installed;
A cleaning liquid reservoir for storing a cleaning liquid for cleaning the inside of the reaction vessel;
A cleaning liquid introduction path for introducing the cleaning liquid into the reaction vessel;
A cleaning liquid discharge passage for discharging the cleaning liquid from the reaction vessel;
An apparatus for synthesizing radioactive chemicals with a cleaning function.

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