WO2012157920A2 - Radioactive compound synthesis system having temperature-control unit - Google Patents

Abstract

There is a need for the development of an apparatus for synthesis of radioactive compounds with high reaction efficiency. More specifically, there is a need for the miniaturization of an apparatus for synthesis, which can also heat and cool the reaction chamber therein. According to the present invention, which is to solve these technical problems, a radioactive compound synthesis system comprises: a radioactive compound synthesis module for synthesizing radioactive compounds therein; and a base unit which is detachably attached to the radioactive compound synthesis module, wherein the radioactive compound synthesis module comprises: a main body provided with a fluid passageway, in the interior, through which a fluid comprising a radioactive isotope, or a substance necessary for synthesis of a radioactive compound is transported, and having a reaction chamber above the fluid passageway; and at least one valve, disposed on the main body, for closing or opening the fluid passageway. The radioactive compound synthesis module is discarded after being used for one round of synthesis, and the base unit comprises a temperature control unit for controlling the temperature of the main body.

Description

Radioactive Compound Synthesis System Including Temperature Control Unit

The present invention relates to a radioactive compound synthesis system, and more particularly to a radiopharmaceutical synthesis system that can be used in PET.

A proton beam of dozens of MeV from the cyclocron is irradiated to the target H ₂ ¹⁸ 0 to produce a radioisotope, ¹⁸ F ion. When the generated ¹⁸ F ion is attached to position 2 of the glucose molecule, it becomes FDG. FDG is a glucose analog (2-deoxy-2- ( ¹⁸ F) fluoro-D-glucose). FDG can be used for proton emission tomography (PET).

According to the prior art (Korean Patent No. 10-1001300), the FDG is produced in a place installed at a remote place or in a hot cell so as to shield radiation from the target of the cyclotron. In general, the distance from the cyclotron target to the hot cell reaches tens of meters. Further, as the pipe is within 1 mm diameter and the ¹⁸ F is transferred to the mixed _{^{H 2 18 0, H 2 18}} 0 being transferred is only 1 ~ 2cc. In many cases, H ₂ ¹⁸ 0 mixed with ¹⁸ F is lost at the connecting portion or the bending portion of the pipe line.

Since high radiation of about 2 Ci or more is detected in 1 to 2 cc of H ₂ ¹⁸ 0, radioactive material leakage and environmental pollution are raised during transfer to the hot cell. Extreme care should be taken because ¹⁸ F is a radionuclide that emits a high energy of 1.2 MeV.

On the other hand, must be transferred to ¹⁸ F is a distance for mixing the H ₂ 0 and ¹⁸ must produce ¹⁸ F having a high radiation keotgi because the risk of loss. Thus, there is a problem that the proton beam must be continuously irradiated for 1 to 2 hours to produce ¹⁸ F having high radioactivity.

On the other hand, in the synthesis of the radioactive compound, the reaction efficiency has a close relationship with the temperature inside the reaction chamber. In general, the reaction chamber is maintained at a temperature of 105 degrees Celsius, and then reacted quickly to obtain a high reaction efficiency. According to the prior art, a heating method using a heating wire or a high frequency heating method is applied to heat the reaction chamber. According to this prior art, a separate cooling means must be added. Then, there is a problem that the configuration becomes more complicated, larger, and the manufacturing cost increases.

There is a need to develop a radioactive compound synthesizing apparatus having high reaction efficiency. More specifically, miniaturization of the synthesis apparatus is required while heating and cooling the reaction chamber of the radioactive compound synthesis apparatus.

Technical problems of the present invention are not limited to the above-mentioned technical problems, and other technical problems that are not mentioned will be clearly understood by those skilled in the art from the following description.

Radioactive compound synthesis system according to the present invention for solving the above technical problem, Radioactive compound synthesis module is synthesized radioactive compound therein; And a base unit detachably coupled to the radioactive compound synthesizing module, wherein the radioactive compound synthesizing module has a flow path that is a fluid passage including a radioisotope or a material required for synthesizing a radioactive compound and is formed therein; A main body having a reaction chamber formed on the flow path; And at least one valve installed in the main body to block or open the flow path, wherein the radioactive compound synthesizing module is used for discarding after synthesizing the radioactive compound once. It includes a temperature control unit for controlling the temperature of.

In addition, the radioisotope may comprise ¹⁸ F.

In addition, the temperature control unit may be configured to heat or cool the inside of the reaction chamber.

In addition, the temperature control unit is configured to heat the inside of the reaction chamber when a current is applied in a first direction, and to cool the inside of the reaction chamber when a current is applied in a second direction opposite to the first direction. Can be.

In addition, the temperature control unit may include a thermoelectric element capable of performing both heating and cooling without a separate cooling device.

In addition, the temperature control unit may include a Peltier element.

In addition, a recess is formed on a lower surface of the main body facing the base unit, and when the radioactive compound synthesizing module and the base unit are coupled, the temperature control unit may be configured to be inserted into the recess.

The concave portion may be formed at a position corresponding to a lower portion of the reaction chamber in the radioactive compound synthesis module.

Since one component enables heating and cooling of the radioactive compound synthesis module, miniaturization is possible, manufacturing costs are low, and reaction efficiency is improved.

The technical effects of the present invention are not limited to the above-mentioned effects, and other technical effects not mentioned will be clearly understood by those skilled in the art from the following description.

1 is a schematic diagram of a radioactive compound synthesis system according to an embodiment of the present invention.

FIG. 2 is a partial cross-sectional view briefly illustrating a process in which ¹⁸ F generated from a target is loaded into an FDG synthesis module.

Figure 3 is a perspective view of the FDG synthesis module and the base unit of the radioactive compound synthesis system according to an embodiment of the present invention.

4 is an exploded perspective view of a radioactive compound synthesis system according to an embodiment of the present invention.

5 is a plan view of a first module of an FDG synthesis module according to an embodiment of the present invention.

6a to 6d are simplified views for explaining the temperature control process of the radioactive compound synthesis system by the temperature control unit.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, the present embodiment is not limited to the embodiments disclosed below, but can be implemented in various forms, and only this embodiment makes the disclosure of the present invention complete, and the scope of the invention to those skilled in the art. It is provided for complete information. Shapes of the elements in the drawings may be exaggerated parts for a more clear description, elements denoted by the same reference numerals in the drawings means the same element.

FDG can be used for proton emission tomography. Isotopes for proton emission tomography include ¹⁸ F, ¹¹ C, ¹⁵ O and ¹³ N. The following describes an example targeting ¹⁸ F. However, the present invention is not limited thereto, and the present invention may also be applied to a radioactive material synthesis module that applies other isotope for tomography.

1 is a schematic configuration diagram of an apparatus for synthesizing a radioactive compound according to an embodiment of the present invention.

The proton beam B accelerated by the cyclotron 100 is irradiated to the target (target apparatus) through the guide tube. The target is filled with H ₂ ¹⁸ 0, and the proton beam B collides with the target to generate ¹⁸ F.

H ₂ ¹⁸ 0 mixed with ¹⁸ F is carried directly into the FDG synthesis module 200 without using a separate intermediate carrier, and FDG is generated through several steps of chemical reactions inside the FDG synthesis module 200. In this regard, in the related art, H ₂ ¹⁸ 0 in which ¹⁸ F is mixed is transported to a synthesis apparatus through a thin long pipe or stored in a separate container to be directly transported by a person. However, the cyclotron 100 and FDG synthesis module 200 for generating a ¹⁸ F a mix of H ₂ ¹⁸ 0 In accordance with the present invention is in one piece.

Accordingly, since H ₂ ¹⁸ 0 may be produced in which ¹⁸ F is mixed to have a relatively weak radioactivity of about 100 to 200 mCi, there is an effect of reducing the risk of radiation exposure. In addition, since the time for irradiating the proton beam can be reduced by that much, productivity is improved.

In addition, since the transport time of the compound is saved, the radioactive compound synthesis time is also reduced to about 15 minutes. Accordingly, there is an effect that can quickly cope with various situations that may occur in the radioactive compound synthesis process.

The base unit 300 may be combined with the FDG synthesis module 200, and may heat or cool the FDG synthesis module 200 to a predetermined temperature.

The control unit 400 may control the base unit 300. In addition, a valve or the like installed in the FDG synthesis module 200 may be controlled.

The control unit 400 may be controlled from a wireless terminal (smartphone, tablet PC, laptop PC) remotely via a wireless communication network.

FIG. 2 is a partial cross-sectional view briefly illustrating a process in which ¹⁸ F generated from a target is loaded into an FDG synthesis module.

Proton beam (B) is a ¹⁸ F is generated and irradiated to the target contained in the target chamber 124 through the inner introducer sheath (110). In this embodiment, the target may be H ₂ ¹⁸ 0. Both sides of the foil block 123 are provided with a first foil 121 and a second foil 122. One side of the target chamber 124 is provided with a cooling chamber 125 for cooling.

An inert gas helium (He) is introduced through the gas inflow passage 126 to push H ₂ ¹⁸ 0 mixed with ¹⁸ F through the discharge passage 127. Then, H ₂ ¹⁸ 0 mixed with ¹⁸ F is loaded into the FDG synthesis module 200 directly connected to the carrying out passage 127. The distance from the end of the discharge passage 127 to the FDG synthesis module 200 is only a few millimeters or a few centimeters. In some cases, even if a connection pipe is installed between the end of the discharge passage 127 and the FDG synthesis module 200, the separation distance may be less than 1 meter.

According to the prior art, a separate compressed air pump or the like is required for the radioactive compound synthesizing apparatus. However, according to the present invention, only one helium supply (not shown) connected to the gas inlet 126 is sufficient for the synthesis and transport of the compound. That is, the flow rate of the compound may be controlled by adjusting the gas pressure using a micro gas flow controller of the synthesis apparatus connected to the compressed helium gas cylinder. Accordingly, there is no need to attach a large-capacity syringe pump, which makes it possible to miniaturize the synthesis apparatus.

The high energy neutron beam may be shielded by installing a plastic body including boron around the target chamber 124. Accordingly, to minimize the neutrons react with H ₂ 0 and ¹⁸ is possible to increase the probability of nuclear reaction between H ₂ 0 and ¹⁸ protons.

The first hole 221a (see FIG. 5) of the FDG synthesis module 200 is detachably installed at the end of the carrying out passage 127, and when coupled, various coupling structures for maintaining watertightness may be applied. . The FDG synthesis module 200 has a width, height, and height of 20 centimeters or less, and in this embodiment, 13 centimeters in width and 11 centimeters in length are manufactured.

3 is a perspective view illustrating a FDG synthesis module and a base unit of a radioactive compound synthesizing apparatus according to an embodiment of the present invention.

As shown in FIG. 3, the FDG synthesis module 200 may be detachably coupled to the base 310 of the base unit 300. The temperature control unit 320 may heat or cool the reaction chambers 229 and 239 of the FDG synthesis module 200 from the outside. The portions of the reaction chambers 229 and 239 of the FDG synthesis module 200 are formed to be thinner than other portions so that the effect of heating or cooling by the temperature control unit 320 may be directly inside the reaction chambers 229.239. Alternatively, the bottom of the FDG synthesis module 200 is formed with a recess in contact with the temperature control unit 320, the temperature control unit 320 may be configured to be inserted into the recess.

4 is an exploded perspective view of a radioactive compound synthesizing apparatus according to an embodiment of the present invention.

As shown in FIG. 4, a radiation detection unit 330 may be installed on an upper surface of the base 310. The through hole 331 may be formed in the radiation detection unit 330 so that the temperature control unit 320 may be exposed upward.

The FDG synthesis module 200 may be detachably installed on the upper surface of the radiation detection unit 330.

The FDG synthesis module 200 includes a lower cover 210, a first module 220, a second module 230, an upper cover 240, a first filter 251, and first to seventh valves 261 to 267. It includes.

The lower cover 210 may have a through hole 211 to allow the temperature control unit 320 to directly contact the bottom surfaces of the reaction chambers 229 and 239 of the first module 220.

The first module 220 is formed with a flow path through which H ₂ ¹⁸ 0 mixed with ¹⁸ F and other samples required for FDG generation can flow, and an insertion groove through which a valve can be installed. In other words, the flow path is a movement path of the material required for synthesizing the radioactive compound.

The lower surface of the second module 230 may be formed in a horizontal plane without concave grooves, or concave grooves may be formed in a shape corresponding to the flow path formed in the first module 220. The first to seventh valve installation grooves 231 to 237 may be formed in the second module 230 such that the first to seventh valves 261 to 267 (thermal melting valves) are installed. The first module 220 and the second module 230 may be formed of a Teflon material or by coating Teflon on an aluminum frame.

First to seventh valve installation grooves 241 to 247 such that the first filter installation grooves 248a and 248b and the first to seventh valves 261 to 267 are installed on the upper cover 240 so that the first filter 251 is installed. ) May be formed.

The first to seventh valves 261 to 267 (thermal melting valves) may be electronic valves controlled electronically by the control unit 400.

As another embodiment, the first to seventh valves may be provided to include a filling part made of a resin weak in heat, and a heater coil surrounding the filling part or inserted into the filling part. Accordingly, in the case of forming a shut-off valve, when the current flows in the heater coil, the filling part may melt and may function as a shut-off valve blocking the flow path. On the other hand, in the case of forming an open valve, the filling part is closed before the current is applied, and when the current is applied to the heater coil, the filling part may be melted to open the flow path.

5 is a plan view of a first module of an FDG generation module according to an embodiment of the present invention.

As shown in FIG. 5, a first hole 221a is formed at one side such that H ₂ ¹⁸ 0 mixed with ¹⁸ F is introduced. H ₂ ¹⁸ 0 ¹⁸ F is mixed may be introduced into the approximately 1 ml is for about 10-15 seconds the first hole (221a). H ₂ ¹⁸ 0 mixed with ¹⁸ F flows to the end of the first flow path 222a formed in the first module 220 and then opens the first hole 238a (see FIG. 4) formed in the second module 230. Through the first filter 251 through.

The first filter 251 fixes ¹⁸ F, while passing the H ₂ ¹⁸ 0. As the first filter 251, AG1-X8 or an anion exchange resin cartridge may be used.

In another embodiment, the first filter may be integrally inserted into the second module.

H ₂ ¹⁸ 0 filtered by ¹⁸ F is carried into the second hole 238b of the second module 230 and flows into the third channel 222c formed in the first module 220. The H ₂ ¹⁸ 0 enters flow into three euros (222c) of the first through the first valve 261 is inserted into the valve mounting groove (223a), and flow to the fourth flow path (222d), the third hole (221c) Can be discharged to the outside.

Further, as the control unit 400 controls the first valve 261 to be switched to the closed state, the third passage 222c and the fourth passage 222d are blocked from each other. Subsequently, the control unit 400 controls the second valve 262 to be switched to the open state so that the third passage 222c and the fifth passage 222e are connected to each other.

^{After 18} F filtered H ₂ ¹⁸ 0 is discharged, TBAHCO 3 (50-100 microliters) and MeOH (about 700 microliters) are introduced into the second passage 222b through the second hole 221b. Accordingly, ¹⁸ F fixed to the first filter 251 flows to the third passage 222c together with TBAHCO 3 and MeOH.

Since the first valve 261 is in a blocked state and the second valve 262 is in an open state, ¹⁸ F flows through the fifth flow path 222e together with TBAHCO 3 and MeOH to reach the reaction chambers 229 and 239. As the control unit 400 controls the third valve 263 to be switched to the closed state, the fifth passage 222e and the reaction chambers 229 and 239 are blocked from each other.

In addition, the control unit 400 controls the temperature control unit 320 to evaporate the remaining amount of H ₂ ¹⁸ 0 by allowing the reaction chambers 229 and 239 to reach 90 degrees Celsius.

Next, mannosetriflate and acetonitril (700 microliters) are introduced into the seventh channel 222g through the fourth hole 221d for about 5 to 10 seconds. When mannosetriflate and acetonitril reach the reaction chambers 229 and 239, the control unit 400 controls the temperature control unit 320 to heat the reaction chambers 229 and 239 to 70 to 80 degrees Celsius. Furthermore, as the control unit 400 controls the fifth valve 265 to be switched to the closed state, the seventh flow path 222g and the reaction chambers 229 and 239 are blocked from each other.

Next, the control unit 400 controls the temperature control unit 320 to cool the reaction chambers 229 and 239 to reach room temperature.

Next, HCl (700 microliters) is introduced into the sixth channel 222f through the fifth hole 221e. When HCl reaches the reaction chambers 229 and 239, the control unit 400 controls the temperature control unit 320 to heat the reaction chambers 229 and 239 to reach 70 to 80 degrees, and then cools them again.

Furthermore, as the control unit 400 controls the fourth valve 264 to be switched to the closed state, the sixth flow path 222f and the reaction chambers 229 and 239 are blocked from each other.

Next, the control unit 400 controls the seventh valve 267 to be switched to the open state, so that the ninth flow path 222i and the reaction chambers 229 and 239 are opened to each other.

Next, the nitrogen gas is introduced into the eighth flow path 222h through the sixth hole 221f to pass through the seventh valve 267 in which the reactants located in the reaction chambers 229 and 239 are opened. It is carried out to 7 holes (221g).

The reactants carried out in the seventh hole (221 g) are transferred to a vial containing KHCO ₃ + H ₂ O and subjected to neutralization. The remaining ¹⁸ F filtered FDG is passed through alumina cartridge to a vial containing saline.

6a to 6d are simplified views for explaining the temperature control process of the radioactive compound synthesis apparatus by the temperature control unit.

Temperature control unit 320 is a component for heating or cooling the FDG synthesis module 200. More specifically, the temperature control unit 320 heats or cools the inside of the reaction chambers 229 and 239 of the FDG synthesis module 200.

The temperature control unit 320 may include a thermoelectric element, in particular a Peltier device using a Peltier effect. A Peltier device is an element that uses the effect of transferring heat from one metal to another when a current flows through two kinds of metal joints. In other words, an exothermic phenomenon occurs in one metal, and an endothermic (cooling) phenomenon occurs in another metal.

FIG. 6A illustrates a process in which the FDG synthesis module 200 and the base unit 300 are coupled to each other. Reaction chambers 229 and 239 are formed in the FDG synthesis module 200 to generate radioactive compounds. Concave portions 200a are formed in portions of the FDG synthesis module 200 corresponding to the lower portions of the reaction chambers 229 and 239.

The temperature control unit 320 may be installed on the upper surface of the base 310. When the FDG synthesis module 200 and the base unit 300 are coupled to each other, the temperature control unit 320 may be inserted into the recess 200a.

6B illustrates a process of heating the interior of the reaction chambers 229 and 239 in a state in which the FDG synthesis module 200 and the base unit 300 are coupled to each other. That is, when the current i flows through the terminal 321 of the temperature control unit 320 in a predetermined direction, an exothermic reaction occurs on the upper surface of the temperature control unit 320. Accordingly, the interior of the reaction chambers 229 and 239 is heated.

6C illustrates a process of cooling the inside of the reaction chambers 229 and 239 in a state in which the FDG synthesis module 200 and the base unit 300 are coupled to each other. That is, when the current i flows in the opposite direction through the terminal 321 of the temperature control unit 320, a cooling reaction (endothermic reaction) occurs on the upper surface of the temperature control unit 320. As a result, the internal temperatures of the reaction chambers 229 and 239 are lowered.

According to the present invention it is possible to switch quickly from the heating mode to the cooling mode only by switching the flow direction of the current has the effect of improving the reaction efficiency. The area of the temperature control unit 320 used in this embodiment is relatively small, about 20 mm 2. Therefore, when the separate heating device and the cooling device are provided respectively, the size of the device becomes very large. However, applying the same temperature control unit 320 as the embodiment of the present invention can significantly reduce the size of the device.

6D illustrates a process in which the FDG synthesis module 200 and the base unit 300 are separated from each other. That is, the FDG synthesis module 200, which has been used after the synthesis reaction is completed, is separated from the base unit 300 for use in subsequent work or for disposal.

An embodiment of the present invention described above and illustrated in the drawings should not be construed as limiting the technical idea of the present invention. The protection scope of the present invention is limited only by the matters described in the claims, and those skilled in the art can change and change the technical idea of the present invention in various forms. Therefore, such improvements and modifications will fall within the protection scope of the present invention as long as it will be apparent to those skilled in the art.

Claims (8)

1. A radioactive compound synthesis module for synthesizing a radioactive compound therein; And

   And a base unit detachably coupled to the radioactive compound synthesis module, wherein the radioactive compound synthesis module includes:

   A body in which a flow path, which is a movement path of a material required for synthesizing a fluid or a radioactive compound including a radioisotope, is formed therein and a reaction chamber is formed on the flow path; And

   And at least one valve installed in the body to block or open the flow path.

   The radioactive compound synthesis module is used for the purpose of discarding after synthesizing the radioactive compound once,

   The base unit is a radioactive compound synthesis system comprising a temperature control unit for controlling the temperature of the body.
2. The method of claim 1,

   The radioisotope comprises ¹⁸ F radioactive compound synthesis system.
3. The method of claim 1,

   Wherein said temperature control unit is configured to heat or cool the interior of said reaction chamber.
4. The method of claim 3,

   The temperature control unit is configured to heat the inside of the reaction chamber when a current is applied in a first direction, and to cool the inside of the reaction chamber when a current is applied in a second direction opposite to the first direction. Radioactive compound synthesis system.
5. The method of claim 3,

   The temperature control unit is a radioactive compound synthesis system, characterized in that it comprises a thermoelectric element capable of performing both heating and cooling without a separate cooling device.
6. The method of claim 3,

   The temperature control unit is a radioactive compound synthesis system, characterized in that it comprises a Peltier element.
7. The method of claim 1,

   A concave portion is formed on a lower surface of the main body facing the base unit, and when the radioactive compound synthesizing module and the base unit are combined, the temperature adjusting unit is configured to be inserted into the concave portion. system.
8. The method of claim 7, wherein

   The recess is a radioactive compound synthesis system, characterized in that formed in a position corresponding to the lower portion of the reaction chamber in the radioactive compound synthesis module.

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