TWI597259B - Device for preparing 18f-labelled glutamate derivatives and the preparation thereof - Google Patents

Description

Apparatus for manufacturing tumor contrast agent of 18 F positron radioisotope marker glutamic acid derivative and preparation method thereof

The present invention relates to a device for manufacturing a tumor contrast agent, and more particularly to a device for automatically synthesizing a tumor contrast agent of a ¹⁸ F positron radioisotope marker glutamic acid derivative, and an automatic synthesis method using the device.

In addition to glucose, tumor cells also highly ingest amino acids, such as glutamine, because of their cellular synthesis needs. The amino acid is generally introduced into the cell by a transporter located on the cell membrane, and includes LAT1 (L-type Amino Acid Transporter 1), ASCT (Alanine Serine Cysteine Transporter) or xCT (Cytine/Glutamate Exchange Transporter). The increase in the performance of these transporters also reflects the deterioration of some cancers and their poor prognosis, such as glioma, lung, prostate and rectum and other organ-related cancers.

Among them, xCT is known to be involved in the biosynthetic pathway of glutathione, and is generally not abundantly expressed in organs except the brain, pancreas, gallbladder and thymus. The performance of xCT is different in different tumor cells, and even has a certain relationship with the degree of tumor cell metastasis and chemical resistance (Chemoresistance) in cancer treatment. In addition, xCT is also thought to have a certain correlation with many oxidative stresses associated with chronic diseases or cancer.

On the other hand, glutaminolysis has recently been recognized as an important target for cancer treatment, and glutathione, which is a precursor of glutamic acid (Glutamate), is more known as cell survival and growth. One of the important factors. Therefore, the fluoro 18-labeled glutamic acid derivative, such as (4S)-4-(3-18Ffluoropropyl)-L-glutamate ([ ¹⁸ F]FSPG, as shown in Figure 1), has also been used as a potential tumor. Positive contrast agents may even serve as a non-invasive prognostic indicator for future malignancies. [ ¹⁸ F]FSPG is not only known to be associated with xCT, but has also been successfully used in clinical practice. According to the current research results, [18F]FSPG is not only well tolerated in patients, but also has excellent tumor detection effect and relatively high TB ratio (Tumor-to-Background Ratios) in clinical diagnosis of liver cancer and lung cancer. ).

The synthesis of [ ¹⁸ F]FSPG is a one-step reaction. First, K ₂₂₂ /K[ ¹⁸ F]F and its precursor (di-tert-butyl(4S)-N-(tert-butoxycarbonyl)-4-(3-{[(4-nitrophenyl)sulfonyl]oxy}propyl )-- L- glutamate) is subjected to a fluorination reaction. Thereafter, hydrolysis reaction was carried out with an appropriate amount of hydrochloric acid to obtain a crude product of [ ¹⁸ F]FSPG (Fig. 2). Finally, after being diluted with water and uniformly mixed, it is purified by a series of solid phase extraction hydrazine to obtain a clinically applicable [ ¹⁸ F]FSPG injection. Among them, purification is often a factor that is difficult to control. In addition, ¹⁸ F for the radiation matter, if the manual were prepared, not only operational problems, less weight once made, can not be mass-produced, and that the personnel need long-term exposure to radiation, their health will be adversely affected. Therefore, in order to reduce the operator dose, an automatic synthesizing device is often used to prepare a large number of ¹⁸ F-labeled positron contrast agents. Among the automatic synthesizers, GE TRACERlab FX has many series, including Fx _FN and Fx _FDG . Among them, the only one that can synthesize [ ¹⁸ F]FSPG is a part of a synthesizer, such as Fx _FN , which has a formulation device. The Fx _FDG synthesizer cannot be directly used to synthesize [ ¹⁸ F]FSPG because it has no relevant equipment (such as a round bottom flask or a magnetic stirring device). Moreover, the radiochemical yield of the [ ¹⁸ F]FSPG synthesis process is unstable (≦1%), so the promotion of the use of [ ¹⁸ F]FSPG in the future will be a very large limitation.

Therefore, in view of the difficulties and limitations derived from the past methods, the inventors have improved and innovated, and after painstaking research, they have successfully developed and manufactured the ¹⁸ F-positive radioisotope-labeled glutamic acid derivative. Synthetic device, successfully improved the existing TracerLab Fx _FDG automatic synthesizer and completed the manufacturing method of the ¹⁸ F positron radioisotope label glutamic acid derivative.

The present invention provides a positive sub ¹⁸ F radioisotope automated synthesis apparatus flag flag of glutamic acid derivative (FIG. 3) may be applied to producing ¹⁸ F flag glutamic acid derivative tumor contrast agent contrast, the manufacturing process is simplified to Meet the needs of clinical research. The invention also provides a method for manufacturing a tumor contrast agent of a marker glutamic acid derivative of the ¹⁸ F positron radioisotope marker by using the device, which is an automated device for manufacturing an ¹⁸ F-mark glutamic acid derivative which can be applied to tumor imaging. To reduce the opportunity for operators to be exposed to radiation.

An apparatus for producing a ¹⁸ F positron radioisotope-labeled glutamic acid derivative, comprising a control device 1 and a reaction system 2; the control device is for automatically controlling a switch of each pipeline in the reaction system; The reaction system comprises a vacuum device 8, a first reagent access device 21, a second reagent access device 22, a third reagent access device 23, a fourth reagent access device 24, and a fifth reagent access. The device 25, a sixth reagent access device 26, a seventh reagent access device 27, an eighth reagent access device 28, a ninth reagent access device 29, a first separating device 31, and a second separation The device 32, a third separating device 33, a fourth separating device 34, a fifth separating device 35, a reaction device 41, a first collector 51, a second collector 52, a third collector 53, a fourth collector 54, and one or more waste storage devices 61, 62; the first separation device 31 is coupled to the first reagent access device 21 for receiving and separating the first reagent access device for storage Solution and place the unwanted solution in a waste The device 61 is stored, and the required reagent is sent to the reaction device 41, and the reaction device is connected to the second to sixth reagent access devices 22, 23, 24, 25, 26 to receive the second to sixth reagents. The solution stored in the device is accessed and reacted, and the radioactive liquid obtained after the reaction is sent to the second collector 52, which is connected to the second and third separating devices 32, 33, and the second collector The solution in 52 will be sent to the second and third separation devices 32, 33 for separation, and the unwanted solution will be placed in a waste storage device 62, which is also identical to the seventh, eighth, and ninth The reagent access devices 27, 28, 29 are connected, and the required reagents are sent to the third collector 53, and the unnecessary solution is also placed in the waste liquid storage device 62, and the third collector 53 is combined with The fourth and fifth separating devices 34, 35 are connected, and the solution in the third collector 53 is sent to the fourth and fifth separating devices 34, 35 for purification and sterilization, and the prepared product is sent to the fourth collector. 54 in standby.

The vacuum device 8 described above includes liquid nitrogen and a vacuum pump.

The first separating device is a QMA column, the second separating device is an HR-P Sep-Pak column, the third separating device is an MCX Sep-Pak column, and the fourth separating device is an Alumina-N Sep-Pak column. The fifth separation device is a microporous membrane.

The second collector described above is a flask, particularly a round bottom flask.

The apparatus further includes at least one helium gas supply means 71, 72, 73, or 74 for generating bubbles for liquid perturbation, in the form of agitation. It can also be used to assist in evaporating the solvent and pushing the liquid. The helium gas supply device 71, 72, 73, or 74 is connected to the first to ninth reagent access devices 21-29, the reaction device 41, the second collector 52, and the third collector 53 through a pipeline, and then transmitted through The switching valve 122, 117, 120, or 121 controls the supply of helium.

The above apparatus additionally includes a cyclotron (not shown).

The apparatus of the present invention differs from prior art apparatus in that a round bottom flask is added and agitation is carried out by means of a bubble to solve the problem of no magnetic stirring. The bubble agitation is a bubble generated by a helium gas blowing method to perform liquid perturbation, and is stirred in the same manner.

The invention further provides an automated synthesis method of a marker glutamic acid derivative of the ¹⁸ F positron radioisotope marker, comprising the steps of: Step 1: transferring a mixed solution of [ ¹⁸ F]fluoride/[ ¹⁸ O]water to a first Collector; Step 2: The mixed solution in the first collector is passed through a first separation device to adsorb the [ ¹⁸ F] fluoride ion, and the [ ¹⁸ O] water is collected into a waste liquid storage device; : passing a solution of K ₂ CO ₃ /aminopolyether _2.2.2 (Kryptofix _2.2.2 ) through the first separation device to bring out the [18F] fluoride ion into a reaction device, and pass it at an appropriate temperature and time Drying with a blunt gas; Step 4: Adding an anhydrous acetonitrile (Acetontrile) solution to the reaction apparatus and drying it at a suitable temperature and time by blunt gas; Step 5: adding a [ ¹⁸ F]FSPG precursor solution to the reaction After the fluorination reaction is carried out in the apparatus at a suitable temperature; after a period of reaction, it is cooled to room temperature; Step 6: the HCl solution is added to the reaction apparatus, and the hydrolysis reaction is carried out at a suitable temperature for a period of time. Then cool to room temperature again; Step 7: Adding water to the reaction device, and collecting the solution in the reaction device into a second collector containing water, and passing nitrogen gas to make the mixing uniform by bubble stirring; Step 8: adding water to the reaction device And collecting the residual product in the reaction device into the second collector; Step 9: passing the solution in the second collector through a second and a third separation device to remove unreacted [ ¹⁸ F] fluorine Ion and precursor and other by-products; Step 10: Washing the third separation device with physiological saline to remove residual organic solvent and impurities in the column; Step 11: Washing the physiological saline again to the third separation device to remove the residual organic solvent; step 12: the phosphate buffer solution through the third separation apparatus, in order to bring out the ^[18 F] FSPG a third product to the collector; and step 13: the product was purified by a fourth And a fifth separating device to bring out the sterilized product to a fourth collector for use.

1‧‧‧Control device

2‧‧‧Reaction system

8‧‧‧vacuum system

21‧‧‧First reagent access device

22‧‧‧Second reagent access device

23‧‧‧ Third reagent access device

24‧‧‧fourth reagent access device

25‧‧‧ fifth reagent access device

26‧‧‧ sixth reagent access device

27‧‧‧ seventh reagent access device

28‧‧‧The eighth reagent access device

29‧‧‧Ninth Reagent Access Device

31‧‧‧First separation device (QMA column)

32‧‧‧Second separation device (HR-P Sep-Pak pipe column)

33‧‧‧The third separation device (MCX Sep-Pak pipe column)

34‧‧‧Four separation device (Alumina-N Sep-Pak pipe column)

35‧‧‧ fifth separation device (microporous membrane)

41‧‧‧Reaction device

51‧‧‧First Collector

52‧‧‧Second collector (round bottom flask)

53‧‧‧ third collector

54‧‧‧fourth collector

61‧‧‧ Waste storage device

62‧‧‧ Waste storage device

71‧‧‧氦 gas supply device

72‧‧‧氦 gas supply device

73‧‧‧氦 gas supply device

74‧‧‧氦 gas supply device

101‧‧‧ switch valve

102‧‧‧ switch valve

103‧‧‧ switch valve

104‧‧‧ switch valve

105‧‧‧Switching valve

106‧‧‧Switching valve

107‧‧‧ switch valve

108‧‧‧Three-way on-off valve

109‧‧‧Three-way on-off valve

110‧‧‧Three-way on-off valve

111‧‧‧Three-way on-off valve

112‧‧‧ switch valve

113‧‧‧ switch valve

114‧‧‧Three-way on-off valve

115‧‧‧Three-way on-off valve

116‧‧‧Switching valve

117‧‧‧ switch valve

118‧‧‧ switch valve

119‧‧‧ switch valve

120‧‧‧Three-way on-off valve

121‧‧‧Three-way switch valve

122‧‧‧Switching valve

Figure 1 is a structural diagram of [ ¹⁸ F]FSPG.

Figure 2 is a two-step reaction formula for [ ¹⁸ F]FSPG synthesis.

Figure 3 is a structural diagram of an automated synthesis apparatus for the marker glutamate derivative of the ¹⁸ F positron radioisotope marker.

Referring to FIG. 3, the device of the present invention comprises a control device 1 and a reaction system 2; the control device is used for automatically controlling the switches of the pipelines in the reaction system; the reaction system comprises a vacuum device 8, a first a reagent access device 21, a second reagent access device 22, a third reagent access device 23, a fourth reagent access device 24, a fifth reagent access device 25, and a sixth reagent access device 26, a seventh reagent access device 27, an eighth reagent access device 28, a ninth reagent access device 29, a first separating device 31, a second separating device 32, a third separating device 33, a fourth separating device 34, a fifth separating device 35, a reaction device 41, a first a collector 51, a second collector 52, a third collector 53, a fourth collector 54, and one or more waste storage devices 61, 62; the first separation device 31 is coupled to the first reagent The access device 21 is connected to receive and separate the solution stored in the first reagent access device, and place the undesired solution in a waste liquid storage device 61, and the required reagent is sent to the reaction device 41, The reaction device is connected to the second to sixth reagent access devices 22, 23, 24, 25, 26 to receive the solution stored in the second to sixth reagent access device and react, and the radioactive liquid obtained after the reaction And being sent to the second collector 52, the second collector 52 is connected to the second and third separating devices 32, 33, and the solution in the second collector 52 is sent to the second and third separating devices 32, 33 for separation, the undesired solution will be placed in a waste storage device 62, which is also connected to the seventh, eighth, and nine reagent access devices 27, 28, 29, and the required reagents are And sent to the third collector 53, the unnecessary solution is also placed in the waste storage device 62, the third collector 53 is connected to the fourth and fifth separating devices 34, 35, and the solution in the third collector 53 is sent to the fourth and fifth separating devices 34, 35 for purification and sterilization. The finished product is sent to the fourth collector 54 for use.

The vacuum device 8 described above includes liquid nitrogen and a vacuum pump.

In a preferred embodiment, the first separating device is a QMA column, the second separating device is a HR-P Sep-Pak column, the third separating device is a MCX Sep-Pak column, and the fourth separating device is Alumina. -N Sep-Pak column, the fifth separation device is a microporous membrane.

The apparatus further comprises at least one helium supply means 71, 72, 73, or 74 for generating bubbles for liquid perturbation, in the form of agitation. It can also be used to assist in evaporating the solvent and pushing the liquid. The helium gas supply device 71, 72, 73, or 74 is connected to the first to ninth reagent access devices 21-29, the reaction device 41, the second collector 52, and the third collector 53 through a pipeline, and The supply of helium is controlled by the on-off valves 122, 117, 120, or 121.

In a preferred embodiment, the helium gas supply device 71 is coupled to the first through ninth reagent access devices 21-29 and controls the helium supply through the switching valve 122. The helium gas supply device 72 is connected to the reaction device 41, and controls the helium gas supply through the switching valve 117. The helium gas supply device 73 is connected to the second collector 52 and controls the helium gas supply through the switching valve 120. The helium gas supply device 74 is connected to the third collector 53 and controls the helium gas supply through the switching valve 121.

In an embodiment, the second collector 52 is a flask. In a preferred embodiment, the flask is a round bottom flask.

The apparatus of the present invention further includes a plurality of on-off valves for controlling the various components. The switching valves 101 to 109 control the first to ninth reagent accessing devices, respectively. In a preferred embodiment, the switching valves 108 and 109 are three-way switching valves.

The number, type, and positional design of the on-off valves can be set as desired and are not limited by the embodiments of the present invention. The on-off valve of the present invention is merely an illustrative example.

In a preferred embodiment, the method for automated synthesis of the glutamate derivative of the ¹⁸ F positron isotope signature of the present invention comprises the steps of: Step 1: Mixing a solution of [ ¹⁸ F]fluoride/[ ¹⁸ O]water Transfer to a first collector; step 2: pass the mixed solution in the first collector through a first separation device to adsorb the [ ¹⁸ F] fluoride ion, and [ ¹⁸ O] water collects a waste liquid a storage device; step 3: passing a solution of K ₂ CO ₃ /aminopolyether _2.2.2 (Kryptofix _2.2.2 ) through the first separation device to bring out the [18F] fluoride ion into a reaction device, and Drying at a suitable temperature and time with an blunt gas; Step 4: drying an anhydrous acetonitrile (Acetontrile) solution into the reaction device and drying it at a suitable temperature and time; Step 5: Adding the precursor solution to the reaction device After the fluorination reaction is carried out at a suitable temperature and time for a period of time, the solution is cooled to room temperature; Step 6: the HCl solution is added to the reaction device, and the hydrolysis reaction is carried out at a suitable temperature for a period of time after the reaction. Cool to room temperature again; Step 7: Will Adding to the reaction device, collecting the product-containing solution into a second collector containing water, and uniformly mixing the mixture by using nitrogen gas; Step 8: adding water to the reaction device, and Collecting residual product in the reaction device into the second collector; Step 9: passing the solution in the second collector through a second and a third separation device to remove unreacted [ ¹⁸ F] fluoride ions and precursors And other by-products; Step 10: washing the third separation device with physiological saline to remove residual organic solvent and impurities in the column; Step 11: washing the physiological saline again to the third separation device to remove a residual organic solvent; step 12: passing the phosphate buffer solution through the third separation device to carry the product into a third collector; and step 13: passing the product through a fourth and a fifth separation device Bring the sterilized product out to a fourth collector for use.

In a preferred embodiment, the appropriate temperature for step 3 is 110 ° C; the appropriate time refers to the point at which all of the solvent is completely evaporated, which may vary depending on the difference between the synthesizer and the supply of the blunt gas, wherein the step The blunt gas is helium or other blunt gas acceptable in the art.

In a preferred embodiment, the appropriate time for step 4 means that all solvents are completely steamed. When to do it.

In a preferred embodiment, the appropriate temperature for step 5 is 70 ° C and the fluorination reaction time is ten minutes.

In a preferred embodiment, the hydrolysis reaction time of the step 6 is ten minutes; the appropriate temperature is 120 °C.

Referring to FIG. 2 and FIG. 3, in a preferred embodiment, the automatic synthesis of [ ¹⁸ F]FSPG includes the following steps: (1) [ ¹⁸ F produced by ¹⁸ O(p,n) ¹⁸ F nuclear reaction An aqueous ion solution, moved from a cyclotron (not shown) to a first collector 51 and filled with helium; (2) vacuuming with a vacuum pump and opening the switch 118 in a vacuum environment, The [ ¹⁸ F] aqueous ion solution is sucked out of the first collector and passed through the three-way switch 110 and the QMA column 31, and then through the three-way switch 111. Finally, the H ₂ ¹⁸ O is recovered to the waste storage device (61). ), while [ ¹⁸ F] ions remain in the QMA column 31; (3) vacuum is applied by a vacuum pump, and the switch 118 is opened in a vacuum environment, and the solution containing K ₂ CO ₃ and Kryptofix _2.2.2 is opened. The first reagent accessor 21 is sucked out, and the [ ¹⁸ F] ions remaining in the QMA column 31 are passed through the three-way switch 110, the QMA column 31, and the three-way switch 111. Putting it out together, flowing into the reaction device 41; (4) evaporating the solution in the reaction device 41 at 110 ° C for 2 minutes, and assisting the solvent drying by flowing helium gas; 5) adding anhydrous acetonitrile in the second reagent accessor 22 to the reaction device 41 under helium gas filling; (6) opening the switch 118 in an evacuated environment, and evaporating the solution at 110 ° C for 2 minutes. And drying with flowing helium; (7) The precursor in the third reagent accessor 23 (di-tert-butyl(4S)-N-(tert-butoxycarbonyl)-4-(3-{[ (4-nitrophenyl)sulfonyl]oxy}propyl)-L-glutamate) (this precursor is dissolved in anhydrous acetonitrile) is added to the reaction containing K[ ¹⁸ F]/Kryptofix _2.2.2 residue by indirect filling of helium. In the apparatus 41; (8) the solution is subjected to a first step of fluorination at 70 ° C; (9) the HCl solution in the fourth reagent accessor 24 is added to the reaction device 41; (10) the solution is The second hydrolysis reaction is carried out at 120 ° C; (11) the H ₂ O in the fifth reagent accessor 25 is added to the reaction device 41; (12) the on-off valve 112 is opened, and the solution in the reactor 41 is The helium gas is filled into the second collector 52 and continuously blown with helium for several minutes; (13) the H ₂ O in the sixth reagent accessor 26 is added to the reaction device 41; (14) Adjusting the switching valve 112 to dissolve the reaction device 41 The helium gas is filled into the second collector 52; (15) the three-way switching valve 120 is turned to the helium source, and the switching valve 113 is adjusted, and the solution at the second collector 52 passes through the HR-P Sep-Pak. The column 32 and the MCX Sep-Pak column 33 are then passed into the waste storage device 62; (16) the three-way switch 114 is adjusted to pass the physiological saline in the seventh reagent accessor 27 through the helium filling through the MCX. a Sep-Pak column 33, and then into the waste storage device 62; (17) passing the physiological saline in the eighth reagent accessor 28 through the MCX Sep-Pak column 33 under helium gas, and then to the waste liquid In the storage device 62; (18) the phosphate buffer in the ninth reagent accessor 29 is passed through the MCX Sep-Pak column 33 and the three-way switch 115 under helium gas filling, and then into the third collector 53, leaving The [ ¹⁸ F]FSPG of the MCX Sep-Pak column 33 is flushed with the phosphate buffer into the third collection device 53; (19) the three-way switch 121 is turned to the helium source, and the on-off valve is adjusted. 116, [ ¹⁸ F]FSPG in physiological saline will pass through the Alumina-N Sep-Pak column 34 and a microporous membrane 35, and then flow to the fourth collector 54 for use.

The stirring time described in the step (12) was 5 minutes.

The cyclotron is an instrument that provides 18F-Fluoride, the front end of device 51 (not shown).

The above-described exemplary embodiments are provided to provide a description of specific aspects of the invention to those skilled in the art. The dosages or operating times described in these examples are not intended to limit the scope of the invention. Without departing from the detailed description, those skilled in the art will be able to utilize the present invention to the extent possible. All published publications cited herein are hereby incorporated by reference in their entirety.

1‧‧‧Control device

2‧‧‧Reaction system

8‧‧‧vacuum system

21‧‧‧First reagent access device

22‧‧‧Second reagent access device

23‧‧‧ Third reagent access device

24‧‧‧fourth reagent access device

25‧‧‧ fifth reagent access device

26‧‧‧ sixth reagent access device

27‧‧‧ seventh reagent access device

28‧‧‧The eighth reagent access device

29‧‧‧Ninth Reagent Access Device

31‧‧‧First separation device (QMA column)

32‧‧‧Second separation device (HR-P Sep-Pak pipe column)

33‧‧‧The third separation device (MCX Sep-Pak pipe column)

34‧‧‧Four separation device (Alumina-N Sep-Pak pipe column)

35‧‧‧ fifth separation device (microporous membrane)

41‧‧‧Reaction device

51‧‧‧First Collector

52‧‧‧Second collector (round bottom flask)

53‧‧‧ third collector

54‧‧‧fourth collector

61‧‧‧ Waste storage device

62‧‧‧ Waste storage device

71‧‧‧氦 gas supply device

72‧‧‧氦 gas supply device

73‧‧‧氦 gas supply device

74‧‧‧氦 gas supply device

101‧‧‧ switch valve

102‧‧‧ switch valve

103‧‧‧ switch valve

104‧‧‧ switch valve

105‧‧‧Switching valve

106‧‧‧Switching valve

107‧‧‧ switch valve

108‧‧‧Three-way on-off valve

109‧‧‧Three-way on-off valve

110‧‧‧Three-way on-off valve

111‧‧‧Three-way on-off valve

112‧‧‧ switch valve

113‧‧‧ switch valve

114‧‧‧Three-way on-off valve

115‧‧‧Three-way on-off valve

116‧‧‧Switching valve

117‧‧‧ switch valve

118‧‧‧ switch valve

119‧‧‧ switch valve

120‧‧‧Three-way on-off valve

121‧‧‧Three-way switch valve

122‧‧‧Switching valve

Claims (8)

The invention relates to a device for manufacturing a tumor contrast agent of a ¹⁸ F positron radioisotope marker glutamic acid derivative, comprising a control device 1 and a reaction system 2; the control device is for automatically controlling a switch of each pipeline in the reaction system; The reaction system comprises a vacuum device 8, a first reagent access device 21, a second reagent access device 22, a third reagent access device 23, a fourth reagent access device 24, and a fifth reagent access. The device 25, a sixth reagent access device 26, a seventh reagent access device 27, an eighth reagent access device 28, a ninth reagent access device 29, a first separating device 31, and a second separation The device 32, a third separating device 33, a fourth separating device 34, a fifth separating device 35, a reaction device 41, a first collector 51, a second collector 52, a third collector 53, a fourth collector 54, and one or more waste storage devices 61, 62; the first separation device 31 is coupled to the first reagent access device 21 for receiving and separating the first reagent access device for storage Solution and place the unwanted solution in one The liquid storage device 61, and the required reagent is sent to the reaction device 41, and the reaction device is connected to the second to sixth reagent access devices 22, 23, 24, 25, 26 to receive the second to sixth The reagent is stored in the solution and reacted, and the radioactive liquid obtained after the reaction is sent to the second collector 52, which is connected to the second and third separating devices 32, 33, and the second collection The solution in the vessel 52 will be sent to the second and third separation devices 32, 33 for separation, and the unwanted solution will be placed in a waste storage device 62, which is also associated with the seventh, eighth, The nine reagent access devices 27, 28, 29 are connected, and the required reagents are sent to the third collector 53, and the unnecessary solution is also placed in the waste storage device 62, and the third collector 53 is The fourth and fifth separating devices 34, 35 are connected, and the solution in the third collector 53 is sent to the fourth and fifth separating devices 34, 35 for purification and sterilization, and the prepared product is sent to the fourth collection. The device 54 is reserved. The apparatus of claim 1, wherein the first separating device is a QMA pipe string, the second separating device is a HR-P Sep-Pak pipe string, and the third separating device is a MCX Sep-Pak pipe string, The fourth separation device is an Alumina-N Sep-Pak column, and the fifth separation device is a microporous membrane. The device of claim 1, wherein the second collector is a flask. The apparatus of claim 3, wherein the flask is a round bottom flask. The apparatus of claim 1, further comprising at least one helium supply device. The device of claim 1, wherein the vacuum device 8 comprises liquid nitrogen and a vacuum pump. For example, the device of claim 1 of the patent scope includes a cyclotron. A method for preparing a tumor contrast agent of ¹⁸ F positron radioisotope marker glutamic acid derivative by using the device of Patent No. 1, comprising the steps of: Step 1: transferring a mixed solution of [ ¹⁸ F] fluoride ion / [ ¹⁸ O] water Up to a first collector; step 2: passing the mixed solution in the first collector through a first separating device to adsorb the [ ¹⁸ F] fluoride ion, and collecting [ ¹⁸ O] water to collect a waste liquid Apparatus; Step 3: passing a solution of K ₂ CO ₃ /aminopolyether _2.2.2 (Kryptofix _2.2.2 ) through the first separation device to carry out the [18F] fluoride ion into a reaction apparatus at a temperature And drying with an blunt gas; Step 4: drying the anhydrous acetonitrile (Acetontrile) solution into the reaction device and drying it at a temperature and time; step 5: adding the precursor solution to the reaction device, and After the fluorination reaction is carried out at a temperature and for a period of time, the solution is cooled to room temperature; Step 6: the HCl solution is added to the reaction device, and the hydrolysis reaction is carried out at a temperature, and then cooled to room temperature after a certain reaction. Step 7: Add water to the reaction pack Putting the solution containing the product into a second collector containing water, and passing the nitrogen gas to make the mixing uniform by bubbles; Step 8: adding water to the reaction device, and the reaction device The internal residual product is collected into the second collector; Step 9: The solution in the second collector is passed through a second and a third separation device to remove unreacted [ ¹⁸ F] fluoride ions and precursors and others By-product; Step 10: Washing the third separation device with physiological saline to remove residual organic solvent and impurities in the column; Step 11: Washing the physiological saline again to the third separation device to remove residual organic a solvent; step 12: passing the phosphate buffer solution through the third separation device to carry the product into a third collector; and step 13: passing the product through a fourth and a fifth separation device to bring out sterilization The product is placed in a fourth collector for later use.