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WO2012157920A2 - Système de synthèse de composés radioactifs comprenant une unité de régulation de température - Google Patents

Système de synthèse de composés radioactifs comprenant une unité de régulation de température Download PDF

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Publication number
WO2012157920A2
WO2012157920A2 PCT/KR2012/003748 KR2012003748W WO2012157920A2 WO 2012157920 A2 WO2012157920 A2 WO 2012157920A2 KR 2012003748 W KR2012003748 W KR 2012003748W WO 2012157920 A2 WO2012157920 A2 WO 2012157920A2
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WO
WIPO (PCT)
Prior art keywords
radioactive compound
control unit
compound synthesis
temperature control
module
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2012/003748
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English (en)
Korean (ko)
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WO2012157920A3 (fr
Inventor
채종서
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sungkyunkwan University
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Sungkyunkwan University
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Filing date
Publication date
Application filed by Sungkyunkwan University filed Critical Sungkyunkwan University
Priority claimed from KR1020120050660A external-priority patent/KR101288867B1/ko
Publication of WO2012157920A2 publication Critical patent/WO2012157920A2/fr
Publication of WO2012157920A3 publication Critical patent/WO2012157920A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G1/00—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
    • G21G1/04—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes outside nuclear reactors or particle accelerators
    • G21G1/10—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes outside nuclear reactors or particle accelerators by bombardment with electrically charged particles

Definitions

  • 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.
  • 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).
  • 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.
  • the distance from the cyclotron target to the hot cell reaches tens of meters.
  • H 2 18 0 being transferred is only 1 ⁇ 2cc.
  • H 2 18 0 mixed with 18 F is lost at the connecting portion or the bending portion of the pipe line.
  • the reaction efficiency has a close relationship with the temperature inside the reaction chamber.
  • the reaction chamber is maintained at a temperature of 105 degrees Celsius, and then reacted quickly to obtain a high reaction efficiency.
  • a heating method using a heating wire or a high frequency heating method is applied to heat the reaction chamber.
  • a separate cooling means must be added. Then, there is a problem that the configuration becomes more complicated, larger, and the manufacturing cost increases.
  • Radioactive compound synthesis system 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.
  • the radioisotope may comprise 18 F.
  • the temperature control unit may be configured to heat or cool the inside of the reaction chamber.
  • 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.
  • the temperature control unit may include a thermoelectric element capable of performing both heating and cooling without a separate cooling device.
  • the temperature control unit may include a Peltier element.
  • 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.
  • FIG. 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.
  • FIG. 4 is an exploded perspective view of a radioactive compound synthesis system according to an embodiment of the present invention.
  • FIG. 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.
  • 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.
  • 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.
  • FIG. 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.
  • 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.
  • 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.
  • 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.
  • the time for irradiating the proton beam can be reduced by that much, productivity is improved.
  • 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.
  • 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.
  • a wireless terminal smart phone, tablet PC, laptop PC
  • 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).
  • 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.
  • a separate compressed air pump or the like is required for the radioactive compound synthesizing apparatus.
  • 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.
  • FIG. 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.
  • 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.
  • 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.
  • FIG. 4 is an exploded perspective view of a radioactive compound synthesizing apparatus according to an embodiment of the present invention.
  • 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.
  • 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.
  • the first to seventh valves 261 to 267 may be electronic valves controlled electronically by the control unit 400.
  • 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.
  • FIG 5 is a plan view of a first module of an FDG generation module according to an embodiment of the present invention.
  • 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.
  • AG1-X8 or an anion exchange resin cartridge may be used as the first filter 251, AG1-X8 or an anion exchange resin cartridge.
  • 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.
  • 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.
  • 18 F flows through the fifth flow path 222e together with TBAHCO 3 and MeOH to reach the reaction chambers 229 and 239.
  • 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.
  • 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.
  • mannosetriflate and acetonitril (700 microliters) are introduced into the seventh channel 222g through the fourth hole 221d for about 5 to 10 seconds.
  • 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.
  • control unit 400 controls the temperature control unit 320 to cool the reaction chambers 229 and 239 to reach room temperature.
  • HCl 700 microliters
  • 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.
  • 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.
  • 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.
  • 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.
  • FIG. 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.
  • 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.
  • FIG. 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.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Nuclear Medicine (AREA)

Abstract

Il existe un besoin de le développement d'un appareil de synthèse de composés radioactifs avec une grande efficacité de réaction, et notamment de miniaturisation d'un appareil de synthèse, qui peut également chauffer et refroidir la chambre de réaction qu'il contient. Selon l'invention, qui vise à résoudre ces problèmes techniques, un système de synthèse de composés radioactifs comprend : un module de synthèse de composés radioactifs pour la synthèse des composés radioactifs qu'il contient; et une unité de base qui est fixée amovible au module de synthèse de composés radioactifs, module comprenant : un corps principal contenant un passage de fluide par lequel un fluide comprenant un isotope radioactif, ou une substance nécessaire à la synthèse d'un composé radioactif, est transporté(e), et possédant une chambre de réaction au-dessus dudit passage de fluide; et au moins une valve, placée sur le corps principal, pour fermer et ouvrir le passage de fluide. Le module de synthèse de composés radioactifs est mis au rebut après avoir été utilisé pour un cycle de synthèse, et l'unité de base comprend une unité de régulation de température pour réguler la température du corps principal.
PCT/KR2012/003748 2011-05-13 2012-05-14 Système de synthèse de composés radioactifs comprenant une unité de régulation de température Ceased WO2012157920A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20110045244 2011-05-13
KR10-2011-0045244 2011-05-13
KR1020120050660A KR101288867B1 (ko) 2011-05-13 2012-05-14 온도조절유닛을 포함하는 방사성 화합물 합성 시스템
KR10-2012-0050660 2012-05-14

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WO2012157920A2 true WO2012157920A2 (fr) 2012-11-22
WO2012157920A3 WO2012157920A3 (fr) 2013-01-24

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Publication number Priority date Publication date Assignee Title
KR101130997B1 (ko) * 2002-12-10 2012-03-28 이온빔 어플리케이션스 에스.에이. 방사성 동위 원소를 생산하기 위한 장치 및 방법
JP4410716B2 (ja) * 2005-03-31 2010-02-03 株式会社日立製作所 放射性同位元素製造装置
US7829032B2 (en) * 2007-01-23 2010-11-09 Siemens Medical Solutions Usa, Inc. Fully-automated microfluidic system for the synthesis of radiolabeled biomarkers for positron emission tomography
WO2008128201A1 (fr) * 2007-04-12 2008-10-23 Siemens Medical Solutions Usa, Inc. Système de radiosynthèse microfluidique pour biomarqueurs de tomographie par émission de positrons
JP2009047454A (ja) * 2007-08-14 2009-03-05 Sumitomo Heavy Ind Ltd Ｒｉ化合物合成装置

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