CN110938041A

CN110938041A - Al (aluminum)18Preparation system and preparation method of F-PSMA-BCH

Info

Publication number: CN110938041A
Application number: CN201911006691.5A
Authority: CN
Inventors: 杨志; 刘特立; 朱华; 杨建华
Original assignee: Beijing Cancer Hospital
Current assignee: Beijing Cancer Hospital
Priority date: 2019-10-22
Filing date: 2019-10-22
Publication date: 2020-03-31

Abstract

The invention relates to the technical field of medicinal chemistry, and provides Al¹⁸The preparation system and the preparation method of the F-PSMA-BCH comprise a first washing unit, an anion exchange column, a fluorination reaction bottle and a purification unit; the first flushing unit is communicated with the anion exchange column; the anion exchange column is communicated with the fluorination reaction bottle through a first pipeline; loading of fluorination reaction vials with a solution containing a precursor compound, AlCl₃And the aqueous solution of a pH buffer agent, and the fluorination reaction bottle outputs the produced Al through a second pipeline¹⁸A purification unit is arranged on a second pipeline of the F-PSMA-BCH aqueous solution; the invention aims at the target aqueous solution through an anion exchange column¹⁸F^‑The product water solution output by the reaction is removed from the free¹⁸F^‑The yield and specific activity of the marked product are improved, the purity of the obtained product water solution is high, and the free product is correspondingly reduced¹⁸F^‑The effect on the diagnostic outcome of the patient.

Description

Al (aluminum)18Preparation system and preparation method of F-PSMA-BCH

Technical Field

The invention relates to the technical field of medicinal chemistry, in particular to Al¹⁸A preparation system and a preparation method of F-PSMA-BCH.

Background

Prostate cancer is currently one of the major diseases threatening the health of men. In China, the incidence of prostate cancer is rising year by year, and most patients are advanced prostate cancer when diagnosed. Early diagnosis and early treatment are always important means for improving the cure rate of tumors and the survival rate of patients.

The Prostate Specific Membrane Antigen (PSMA) is specifically and highly expressed in prostate cancer and metastatic focus cells thereof, and is obviously related to the malignant condition of tumors. In recent years, small molecule probes targeting PSMA have been extensively studied⁶⁸Ga and¹⁸the F-labeled molecular probe is mainly used. Relative to⁶⁸In the case of Ga, the molecular weight of the alloy,¹⁸f has its unique advantages, such as moderate half-life (109.7 min); prepared by an accelerator and has large yield (>4 Ci); high spatial resolution (being the highest of all positron species), etc., which results in¹⁸F-labeled molecular probes have been a feature of research. But are relative to⁶⁸Ga labels, conventional¹⁸The F labeling method has the defects of long labeling time, high reaction temperature, strict requirement on no water, low labeling rate and the like.

"Al" as described in patent application No. 201710368982.3¹⁸F-labeled PSMA (PSMA) targeted inhibitor, preparation method and application thereof ", Al¹⁸The F-PSMA-BCH is marked mainly by adopting a manual marking method because¹⁸F manual labeling has a limited yield, while the concentration has a large influence on the labeling rate, and a large amount of carrier-free material is usually loaded and eluted in the labeling process¹⁸F-, and actually only one fourth to one fifth of the amount of the Al is needed to be used in the marking process, so that Al is prepared¹⁸F-PSMA-BCH may require removal of large amounts of free carrier-free material¹⁸F-, which greatly increases the radioactivity to which the operator is exposed directly, and the operator is often exposed to radiation damage due to unnecessary overexposure.

Disclosure of Invention

Technical problem to be solved

The invention aims to provide Al¹⁸A preparation system and a preparation method of F-PSMA-BCH, which are used for solving the problem of Al in the prior art¹⁸F-PSMA-BCH manual operation¹⁸The F labeling method has the problems of limited yield, high radioactivity of operators in contact with the F labeling method, high radiation dose received by the F labeling method and radiation damage to human bodies.

(II) technical scheme

In order to solve the technical problem, the invention provides Al¹⁸The preparation system of the F-PSMA-BCH comprises a first washing unit, an anion exchange column, a fluorination reaction bottle and a purification unit;

the first flushing unit is communicated with the anion exchange column;

the anion exchange column is used for capturing target aqueous solution¹⁸F^-The anion exchange column is communicated with the fluorination reaction bottle through a first pipeline;

the fluorination reaction bottle is internally provided with a precursor compound and AlCl₃And a pH buffer solution, wherein the fluorination reaction bottle outputs the produced Al through a second pipeline¹⁸The F-PSMA-BCH aqueous solution is arranged on the second pipeline, and the purification unit is arranged on the second pipeline;

the purification unit is used for removing Al output by reaction¹⁸Free in F-PSMA-BCH aqueous solution¹⁸F^-。

Preferably, the purification unit of the present invention comprises a solid phase extraction column and a second washing unit, wherein the solid phase extraction column is installed on the second pipeline; the second washing unit comprises a first penicillin bottle and a third pipeline, and elution solution is arranged in the first penicillin bottle; one end of the third pipeline is communicated with the first penicillin bottle, and the other end of the third pipeline is communicated with the second pipeline between the fluorination reaction bottle and the solid-phase extraction column.

Preferably, the purification unit further comprises an aseptic filter membrane, the aseptic filter membrane is installed on the second pipeline and located between the solid phase extraction column and the output end of the second pipeline, and the output end of the second pipeline is connected with a product bottle.

Preferably, the first washing unit comprises a second penicillin bottle and a fourth pipeline, wherein the second penicillin bottle is loaded with physiological saline and is communicated with the anion exchange column through the fourth pipeline.

Preferably, a six-way valve is arranged between the first flushing unit and the anion exchange column; the first valve port of the six-way valve is communicated with an O18 water recovery bottle through a fifth pipeline, the second valve port of the six-way valve is used for introducing the target water solution, the anion exchange column is connected in series between the third valve port and the sixth valve port of the six-way valve through a pipeline, the fourth valve port of the six-way valve is communicated with one end, far away from the second penicillin bottle, of the fourth pipeline, the fifth valve port of the six-way valve is communicated with one end of the first pipeline, and the other end of the first pipeline is communicated with the fluorination reaction bottle.

Preferably, in the invention, the middle part of the first pipeline is respectively communicated with a first branch pipe and at least one second branch pipe, one end of the first branch pipe, which is far away from the first pipeline, is communicated with a third cillin bottle, one end of the second branch pipe, which is far away from the first pipeline, is communicated with a fourth cillin bottle, and the third cillin bottle and the fourth cillin bottle are loaded with purified water.

Preferably, the invention also comprises a fifth penicillin bottle and a waste liquid bottle; the fifth penicillin bottle is communicated with the first penicillin bottle through a sixth pipeline and is loaded with physiological saline; the second pipeline between the solid-phase extraction column and the sterile filter membrane is communicated with one end of a seventh pipeline, and the other end of the seventh pipeline is communicated with the waste liquid bottle; the waste liquid bottle is also communicated with the fluorination reaction bottle through an eighth pipeline.

Preferably, the invention further comprises an inert gas feeding system, wherein the inert gas feeding system comprises a gas inlet pipe, a gas cavity and a plurality of gas outlet pipes, the gas inlet pipe is communicated with the gas cavity, the gas cavity is communicated with one ends of the plurality of gas outlet pipes, and the other ends of the plurality of gas outlet pipes are respectively communicated with the first penicillin bottle, the second penicillin bottle, the third penicillin bottle, the fourth penicillin bottle and the fifth penicillin bottle which are provided with pressing covers.

Preferably, the tube body of the air inlet tube close to the air inlet end of the air inlet tube is connected with one end of a bronchus, and the other end of the bronchus is communicated with the second pipeline between the fluorination reaction bottle and the solid-phase extraction column; the butt joint part of the air inlet pipe and the bronchus is provided with an air flow meter, the bronchus is provided with a one-way valve, and the butt joint part of the bronchus and the second pipeline is provided with a three-way valve.

The invention also provides Al based on the preparation system¹⁸The preparation method of the F-PSMA-BCH comprises the following steps:

s1, capturing¹⁸F^-To be captured¹⁸F^-Adding to a fluorination reaction flask loaded with an aqueous solution of a precursor compound, AlCl3, and a pH buffer to perform the fluorination reaction;

s2, removing Al output after the reaction of the fluorination reaction bottle¹⁸Free in F-PSMA-BCH aqueous solution¹⁸F^-。

Preferably, the present invention comprises capturing H using an anion exchange column in step S1¹⁸In aqueous solution of F target¹⁸F^-And washing the captured on the anion exchange column with physiological saline¹⁸F^-To be captured¹⁸F^-Adding into a fluorination reaction bottle.

Preferably, the present invention comprises capturing Al in the reaction output solution from the fluorination reaction flask by using a solid phase extraction column in step S2¹⁸F-PSMA-BCH for discharging free substances in output solution¹⁸F^-Then, the second washing unit extracts Al captured on the solid phase extraction column through the elution solution¹⁸F-PSMA-BCH is flushed to obtain free¹⁸F^-Al of (2)¹⁸F-PSMA-BCH aqueous solution.

Preferably, the chemical structure of the precursor compound in the present invention is:

the pH buffering agent is potassium hydrogen phthalate; the precursor compound and AlCl in the fluorination reaction bottle₃And the mol ratio of the pH buffering agent is 1: 0.6: 22.

(III) technical effects

Al provided by the invention¹⁸The preparation system and the preparation method of the F-PSMA-BCH capture target aqueous solution by adopting an anion exchange column¹⁸F^-After the first washing unit washes the anion exchange column, the first washing unit comprises¹⁸F^-Is delivered into the fluorination reaction bottle and is mixed with the precursor compound and AlCl loaded in the fluorination reaction bottle₃Are subjected to fluorination reaction together with the aqueous solution of (a) to obtain the produced Al¹⁸F-PSMA-BCH aqueous solution, and meanwhile, when the product is output, Al output by the reaction is further removed through a purification unit¹⁸Free in F-PSMA-BCH aqueous solution¹⁸F^-。

As can be seen from the above, the present invention ensures the targeting of an aqueous solution in which the target is present through an anion exchange column¹⁸F^-Thereby ensuring Al in the fluorination reaction¹⁸The labeling rate of F-PSMA-BCH is increased, and Al output by the reaction is removed by a purification unit¹⁸Free in F-PSMA-BCH aqueous solution¹⁸F^-The yield and specific activity of the marked product are improved, the purity of the obtained product aqueous solution is high, the radioactivity of the operator in contact with the product in the whole preparation process is greatly reduced, and the free radioactivity is correspondingly reduced¹⁸F^-The imaging is influenced, so that the accuracy of the diagnosis result of the patient is ensured.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.

FIG. 1 shows Al in example 1 of the present invention¹⁸The structure schematic diagram of the F-PSMA-BCH preparation system;

FIG. 2 shows Al in example 2 of the present invention¹⁸A structural block diagram of a preparation method of F-PSMA-BCH;

FIG. 3 is a drawing showingAl prepared in inventive example 2¹⁸And (3) a high performance liquid chromatography radioactive component result chart of the F-PSMA-BCH solution.

In the figure: 1-a first penicillin bottle, 2-a second penicillin bottle, 3-a third penicillin bottle, 4-a fourth penicillin bottle, 5-a fifth penicillin bottle, 6-a fluorination reaction bottle, 7-a product bottle, 8-O18 water recovery bottle, 9-a waste liquid bottle, 10-a first pipeline, 11-a second pipeline, 12-a third pipeline, 13-a fourth pipeline, 14-a fifth pipeline, 15-a sixth pipeline, 16-a seventh pipeline, 17-an eighth pipeline, 18-a first branch pipe, 19-a second branch pipe, 20-an anion exchange column, 21-a six-way valve, 22-a solid phase extraction column, 23-a sterile filter membrane, 24-an air inlet pipe, 25-an air cavity, 26-an air outlet pipe, 27-a branch pipe and 28-an air flow meter.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

In the description of the present invention, it should be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral connection; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meanings of the above terms in the present invention can be understood in specific cases to those skilled in the art.

In the case of the example 1, the following examples are given,

referring to fig. 1, the present embodiment provides an Al¹⁸The preparation system of the F-PSMA-BCH comprises a first washing unit, an anion exchange column 20, a fluorination reaction bottle 6 and a purification unit;

the first flushing unit is communicated with the anion exchange column 20;

the anion exchange column 20 is used for trapping target aqueous solution¹⁸F^-The anion exchange column 20 is communicated with the fluorination reaction bottle 6 through a first pipeline 10;

the fluorination reaction bottle 6 is internally provided with a precursor compound and AlCl₃And pH buffer, the fluorination reaction bottle 6 outputs the produced Al through a second pipeline 11¹⁸A purification unit is arranged on the second pipeline 11 of the F-PSMA-BCH aqueous solution;

As is clear from the structure shown in FIG. 1, this example realizes the effect of the anion exchange column 20 on the target aqueous solution¹⁸F^-After the first washing unit washes the anion exchange column, the capture solution will contain¹⁸F^-Is delivered into the fluorination reaction flask 6 and reacts with the precursor compound and AlCl loaded in the fluorination reaction flask₃Are subjected to fluorination reaction together with the aqueous solution of (a) to obtain the produced Al¹⁸F-PSMA-BCH aqueous solution, and meanwhile, Al output by reaction is further removed through a purification unit when products are output¹⁸Free in F-PSMA-BCH aqueous solution¹⁸F^-。

Through the preparation system shown in the embodiment, the yield and specific activity of the marked product are effectively improved, and the purity of the obtained product water solution is high. In addition, in the whole preparation process, operators are not required to contact all links of the whole preparation operation basically (or contact less), so that the contact radioactivity of the operators is greatly reduced, the radiation damage of the operators due to unnecessary overexposure is effectively prevented, and the personal safety of the operators is ensured.

At the same time, the obtained product is free in aqueous solution¹⁸F^-Is smaller, thereby reducing the free¹⁸F^-The influence on the imaging is further ensured, and the accuracy of the diagnosis result of the patient is further ensured.

Further, the purification unit in this embodiment includes a solid phase extraction column 22 and a second washing unit, the solid phase extraction column 22 is installed on the second pipeline 11; the second washing unit comprises a first penicillin bottle 1 and a third pipeline 12, wherein the first penicillin bottle 1 is loaded with an elution solution, and the elution solution is an 80% ethanol solution for eluting products; one end of the third pipeline 12 is communicated with the first penicillin bottle 1, and the other end is communicated with the second pipeline 11 between the fluorination reaction bottle 6 and the solid phase extraction column 22.

From this, it can be seen that the purification unit is on Al output to the reaction¹⁸When the F-PSMA-BCH aqueous solution is purified, the solid phase extraction column 22 is firstly adopted to capture Al in the reaction output solution¹⁸F-PSMA-BCH for discharging free substances in output solution¹⁸F^-Then the elution solution loaded by the first penicillin bottle 1 is used for extracting Al captured on the solid phase extraction column 22¹⁸F-PSMA-BCH is flushed to obtain free¹⁸F^-Al of (2)¹⁸F-PSMA-BCH aqueous solution.

Further, to realize elution of the obtained Al¹⁸The crude product of F-PSMA-BCH is further filtered, in this embodiment, a sterile filter membrane 23 is further disposed in the purification unit, the sterile filter membrane 23 is mounted on the second pipeline 11 and is located between the solid-phase extraction column 22 and the output end of the second pipeline 11, the output end of the second pipeline 11 is connected to the product bottle 7, and the finally obtained product bottle 7 without containing F is collected¹⁸F^-Al of (2)¹⁸F-PSMA-BCH aqueous solution.

Further, in the present embodiment, the first washing unit includes a second vial 2 and a fourth pipeline 13, the second vial 2 is loaded with physiological saline and is communicated with the anion exchange column 20 through the fourth pipeline 13, so that the physiological saline loaded by the second vial 2 can be used to capture the saline on the anion exchange column 20¹⁸F^-Rinsing, and after rinsing, adding¹⁸F^-Is fed to the fluorination reaction vessel 6 through a first line 10.

Further, in this embodiment, a six-way valve 21 is disposed between the first flushing unit and the anion exchange column 20; the first valve port of the six-way valve 21 is communicated with the O18 water recovery bottle 8 through a fifth pipeline 14, the second valve port of the six-way valve 21 is used for introducing the target water solution, an anion exchange column 20 is connected between the third valve port and the sixth valve port of the six-way valve 21 in series through a pipeline, the fourth valve port of the six-way valve is communicated with one end of the fourth pipeline 13 far away from the second penicillin bottle 2, the fifth valve port of the six-way valve 21 is communicated with one end of the first pipeline 10, and the other end of the first pipeline 10 is communicated with the fluorination reaction bottle 6.

Specifically, in actual practice, the H-containing material prepared from SUMITOMO HM20 medical cyclotron¹⁸F, the target water solution (with the radioactivity of 37GBq) is introduced into the six-way valve 21 through the second valve port, and is captured by the anion exchange column 20 when flowing through the pipeline between the third valve port and the sixth valve port¹⁸F^-And the physiological saline is introduced into the six-way valve 21 through the fourth valve port, so that the physiological saline can be captured on the anion exchange column 20¹⁸F^-Washing off the components, the obtained product contains¹⁸F^-The water solution is conveyed to the fluorination reaction bottle 6 through a first pipeline 10, and O18 water generated in the process enters an O18 water recovery bottle 8 through a fifth pipeline 14 for unified recovery.

Further, in this embodiment, the middle portion of the first pipeline 10 is respectively communicated with a first branch pipe 18 and at least one second branch pipe 19 (specifically, two second branch pipes 19 may be provided), one end of the first branch pipe 18, which is far away from the first pipeline 10, is communicated with the third penicillin bottle 3, one end of the second branch pipe 19, which is far away from the first pipeline 10, is communicated with the fourth penicillin bottle 4, and the third penicillin bottle 3 and the fourth penicillin bottle 4 are loaded with purified water.

Specifically, after the fluorination reaction is completed in the fluorination reaction bottle 6, the reaction product in the fluorination reaction bottle 6 can be diluted through the third penicillin bottle 3, the first branch pipe 18 and the first pipeline 10. At the same time, Al is produced in the reaction¹⁸When the F-PSMA-BCH aqueous solution is purified, Al trapped in the solution can be respectively conveyed by the purified water in a plurality of (specifically two) fourth penicillin bottles 4 through corresponding pipelines¹⁸The solid phase extraction column 22 of F-PSMA-BCH is washed several times (twice), so that the unreacted components can be effectively removed¹⁸F^-And completely washing the product, so that the radiochemical purity of the product is improved, wherein the radiochemical purity of the product is more than 99 percent and meets the injection standard.

Further, the embodiment also comprises a fifth penicillin bottle 5 and a waste liquid bottle 9; the fifth penicillin bottle 5 is communicated with the first penicillin bottle 1 through a sixth pipeline 15, a one-way valve is arranged on the sixth pipeline 15, and the fifth penicillin bottle 5 is loaded with physiological saline; a second pipeline 11 between the solid-phase extraction column 22 and the sterile filter membrane 23 is communicated with one end of a seventh pipeline 16, and the other end of the seventh pipeline 16 is communicated with a waste liquid bottle 9; the waste liquid bottle 9 is also communicated with the fluorination reaction bottle 6 through an eighth pipeline 17.

Therefore, Al is captured by the pure water¹⁸When the solid phase extraction column 22 of F-PSMA-BCH is washed for a plurality of times, the obtained solution contains¹⁸F^-Can be collected in the waste bottle 9 through a seventh line 16.

Washing the solid phase extraction column 22 by the elution solution loaded in the first penicillin bottle 1 to obtain Al¹⁸The F-PSMA-BCH aqueous solution is finally collected in the product bottle 7 after being filtered by the sterile filter membrane 23.

Further, after the physiological saline in the fifth penicillin bottle 5 is transferred to the first penicillin bottle 1 through the sixth pipeline 15, the physiological saline is transferred to the product bottle 7 through the third pipeline 12 and the second pipeline 11 again to carry out Al treatment on the product bottle 7¹⁸Diluting the F-PSMA-BCH aqueous solution.

Further, the embodiment further comprises an inert gas feeding system, wherein the inert gas fed into the inert gas feeding system is N₂The inert gas feeding system comprises an air inlet pipe 24, an air cavity 25 and a plurality of air outlet pipes 26, the air inlet pipe 24 is communicated with the air cavity 25, the air cavity 25 is communicated with one ends of the air outlet pipes 26, and the other ends of the air outlet pipes 26 are respectively communicated with a first penicillin bottle 1, a second penicillin bottle 2, a third penicillin bottle 3, a fourth penicillin bottle 4 and a fifth penicillin bottle 5 which are provided with pressing covers.

Specifically, the inert gas feed system employs N₂The driving force for outputting the liquid in each penicillin bottle is realized, and the influence on the chemical reaction of the whole preparation system is prevented.

Further, in this embodiment, the tube body of the air inlet tube 24 near the air inlet end thereof is connected to one end of the bronchus 27, and the other end of the bronchus 27 is communicated with the second pipeline 11 between the fluorination reaction bottle 6 and the solid-phase extraction column 22; an airflow meter 28 is arranged at the butt joint part of the air inlet pipe 24 and the branch pipe 27, a one-way valve is arranged on the branch pipe 27, and a three-way valve is arranged at the butt joint part of the branch pipe 27 and the second pipeline 11.

Specifically, the flow of the supplied gas is monitored by the airflow meter 28, so that the inert gas satisfying the air pressure can be supplied to the whole preparation system, and the branch gas pipe 27 is arranged between the gas inlet pipe 24 and the second pipeline 11, so that the residual waste liquid in the fluorination reaction bottle 6 can be discharged to the waste liquid bottle 9 through the eighth pipeline 17 by supplying the gas to the fluorination reaction bottle 6 after the fluorination reaction is completed in the fluorination reaction bottle 6.

In addition, it should be noted here that in this example, the anion exchange column 20 used was a Sep Pak QMA column, the solid phase extraction column 22 used was a Sep Pak C18 column manufactured by BIO-RAD, and the sterile filtration membrane 23 used was a sterile filtration membrane manufactured by Merck Millipore.

Electromagnetic valves are respectively arranged at the head end and the tail end of the first pipeline 10, the first branch pipe 18, the second branch pipe 19, one end of the second pipeline 11 close to the fluorination reaction bottle 6 and the eighth pipeline 17; corresponding air valves are arranged on the air inlet pipe 24 and the air outlet pipe 26, and three-way valves are arranged at the butt joint part of the third pipeline 12 and the second pipeline 11 and the butt joint part of the seventh pipeline 16 and the second pipeline 11.

In the case of the example 2, the following examples are given,

this example is based on Al described in example 1¹⁸A preparation system of F-PSMA-BCH, in particular to Al¹⁸The preparation method of the F-PSMA-BCH, as shown in FIG. 2, comprises the following steps:

Further, this embodiment includes capturing H using the anion exchange column 20 in step S1¹⁸In aqueous solution of F target¹⁸F^-And will beThe second penicillin bottle 2 is loaded with 0.4mL of physiological saline to wash the captured on the anion exchange column 20¹⁸F^-To be captured¹⁸F^-Adding into a fluorination reaction bottle 6, wherein the elution efficiency can reach more than 90 percent by using 0.4mL of physiological saline under the condition of ensuring the minimum volume, thereby not only improving¹⁸F^-The elution efficiency and the volume of the solution for the fluorination reaction are effectively reduced, so that the higher marking rate is ensured, the temperature for the fluorination reaction in the fluorination reaction bottle 6 is 110 ℃, and the reaction time is 15 min.

Further, between the step S1 and the step S2, 5mL of purified water loaded in the third penicillin bottle 3 is added into the fluorination reaction bottle 6 through a corresponding pipeline to dilute the solution after the fluorination reaction.

Further, in step S2, this embodiment further includes the following steps:

first, the solid phase extraction column 22 is used to capture Al in the reaction output solution from the fluorination reaction flask 6¹⁸F-PSMA-BCH for discharging free substances in output solution¹⁸F^-Wherein the free in the output solution is discharged¹⁸F^-The operation of (1) is to drip wash the solid phase extraction column 22 one by one through the corresponding pipeline by 5mL of purified water loaded by each fourth penicillin bottle 4, and the drip wash is carried out for two times, so that unreacted pure water can be used for washing the solid phase extraction column 22 for two times¹⁸F^-Discharging;

secondly, the solid phase extraction column 22 is eluted by 1.5mL of 80% ethanol solution loaded in the first penicillin bottle 1, so as to capture Al on the solid phase extraction column 22¹⁸F-PSMA-BCH is flushed to obtain free¹⁸F^-Al of (2)¹⁸F-PSMA-BCH aqueous solution.

Further, after the step S2, the method further includes the step of adding Al loaded in the product bottle 7 in the step S2¹⁸Diluting an aqueous solution of F-PSMA-BCH:

the 5mL of physiological saline loaded in the fifth vial 5 is transferred into the first vial 1 and transferred to the product vial 7 through the third line 12 and the second pipe 11.

Further, the fluorination reaction flask in this embodiment6 internal precursor Compound, AlCl₃And the mol ratio of the pH buffering agent is 1: 0.6: 22, the concentration of the precursor compound can be set to be 4mmol/L, and AlCl can be set to be specific₃The concentration of the solution (2) and the concentration of the pH buffer (0.5 mol/L) were determined. By directly reacting a precursor compound with AlCl during the fluorination reaction₃The pH buffer is added into the fluorination reaction bottle 6, so that the precursor compound and the AlCl can be ensured while the volume of the reaction solution is reduced₃The ratio of (a) is unchanged, the labeling rate can be effectively ensured, and the labeling rate can be further ensured by controlling the pH value of the reaction solution in the fluorination reaction flask 6 to be about 4.0 by a pH buffer, wherein the chemical structure of the precursor compound is as follows:

the pH buffering agent is potassium hydrogen phthalate.

After the reaction is finished, identifying the Al18F-PSMA-BCH product solution by adopting a high performance liquid chromatography, wherein the chromatographic conditions are as follows: the stationary phase adopts a ZORBAX eclipse C18 column (4.6X 250 mm); the mobile phase adopts water (phase A) containing 0.1 percent of trifluoroacetic acid and acetonitrile (phase B) containing 0.1 percent of trifluoroacetic acid respectively, and gradient elution is carried out (0-10 min: 5-60 percent of B, 10-15 min: 60-5 percent of B); the flow rate is 1 mL/min; the analysis result is shown in figure 3, the retention time of the main radioactive component in the product solution is 9.834 minutes, thereby showing that the Al18F-PSMA-BCH solution obtained by the reaction meets the injection requirement.

The above-described embodiments of the apparatus are merely illustrative, and the units described as separate parts may or may not be physically separate, and parts displayed as units may or may not be physical units, may be located in one place, or may be distributed on a plurality of network units. Some or all of the modules may be selected according to actual needs to achieve the purpose of the solution of the present embodiment. One of ordinary skill in the art can understand and implement it without inventive effort.

Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.

Claims

1. Al (aluminum)¹⁸The preparation system of F-PSMA-BCH is characterized by comprising a first washing unit, an anion exchange column, a fluorination reaction bottle and a purification unit;

the first flushing unit is communicated with the anion exchange column;

2. Al according to claim 1¹⁸The preparation system of F-PSMA-BCH is characterized in that the purification unit comprises a solid phase extraction column and a second washing unit, and the solid phase extraction column is arranged on the second pipeline; the second washing unit comprises a first penicillin bottle and a third pipeline, and elution solution is arranged in the first penicillin bottle; one end of the third pipeline is communicated with the first penicillin bottle, and the other end of the third pipeline is communicated with the second pipeline between the fluorination reaction bottle and the solid-phase extraction column.

3. Al according to claim 2¹⁸The preparation system of F-PSMA-BCH, characterized in that, purification unit still includes aseptic filter membrane, aseptic filter membrane install in the second pipeline to be located the solid phase extraction post with between the output of second pipeline, the output of second pipeline is connected the product bottle.

4. Al according to claim 2¹⁸The preparation system of the F-PSMA-BCH is characterized in that the first flushing unit comprises a second penicillin bottle and a fourth pipeline, wherein the second penicillin bottle is loaded with physiological saline and is communicated with the anion exchange column through the fourth pipeline.

5. Al according to claim 4¹⁸The preparation system of F-PSMA-BCH is characterized in that a six-way valve is arranged between the first flushing unit and the anion exchange column; the first valve port of the six-way valve is communicated with an O18 water recovery bottle through a fifth pipeline, the second valve port of the six-way valve is used for introducing the target water solution, the anion exchange column is connected in series between the third valve port and the sixth valve port of the six-way valve through a pipeline, the fourth valve port of the six-way valve is communicated with one end, far away from the second penicillin bottle, of the fourth pipeline, the fifth valve port of the six-way valve is communicated with one end of the first pipeline, and the other end of the first pipeline is communicated with the fluorination reaction bottle.

6. Al according to claim 5¹⁸The preparation system of F-PSMA-BCH is characterized in that the middle of the first pipeline is respectively communicated with a first branch pipe and at least one second branch pipe, one end, far away from the first pipeline, of the first branch pipe is communicated with a third Xilin bottle, one end, far away from the first pipeline, of the second branch pipe is communicated with a fourth Xilin bottle, and the third Xilin bottle and the fourth Xilin bottle are loaded with purified water.

7. Al according to claim 6¹⁸The preparation system of the F-PSMA-BCH is characterized by further comprising a fifth penicillin bottle and a waste liquid bottle; the fifth penicillin bottle is communicated with the sixth penicillin bottle through a sixth pipelineA penicillin bottle, wherein the fifth penicillin bottle is loaded with physiological saline; the second pipeline between the solid-phase extraction column and the sterile filter membrane is communicated with one end of a seventh pipeline, and the other end of the seventh pipeline is communicated with the waste liquid bottle; the waste liquid bottle is also communicated with the fluorination reaction bottle through an eighth pipeline.

8. Al according to claim 7¹⁸The preparation system of the F-PSMA-BCH is characterized by further comprising an inert gas feeding system, wherein the inert gas feeding system comprises a gas inlet pipe, a gas cavity and a plurality of gas outlet pipes, the gas inlet pipe is communicated with the gas cavity, the gas cavity is communicated with one ends of the plurality of gas outlet pipes, and the other ends of the plurality of gas outlet pipes are respectively communicated with the first penicillin bottle, the second penicillin bottle, the third penicillin bottle, the fourth penicillin bottle and the fifth penicillin bottle which are provided with pressing covers.

9. Al according to claim 8¹⁸The preparation system of the F-PSMA-BCH is characterized in that a pipe body of the air inlet pipe, which is close to the air inlet end of the air inlet pipe, is connected with one end of a bronchus, and the other end of the bronchus is communicated with the second pipeline between the fluorination reaction bottle and the solid-phase extraction column; the butt joint part of the air inlet pipe and the bronchus is provided with an air flow meter, the bronchus is provided with a one-way valve, and the butt joint part of the bronchus and the second pipeline is provided with a three-way valve.

10. Al according to any of claims 1 to 9¹⁸Al of F-PSMA-BCH preparation system¹⁸The preparation method of the F-PSMA-BCH is characterized by comprising the following steps:

s1, capturing¹⁸F^-To be captured¹⁸F^-Added to the precursor compound, AlCl₃And an aqueous solution of a pH buffer in a fluorination reaction flask to perform a fluorination reaction;

11. The method of claim 10, wherein step S1 includes trapping H with an anion exchange column¹⁸In aqueous solution of F target¹⁸F^-And washing the captured on the anion exchange column with physiological saline¹⁸F^-To be captured¹⁸F^-Adding into a fluorination reaction bottle.

12. The method of claim 10, wherein step S2 comprises capturing Al in the reaction output solution from the fluorination reaction vessel by using a solid phase extraction column¹⁸F-PSMA-BCH for discharging free substances in output solution¹⁸F^-Then, the second washing unit extracts Al captured on the solid phase extraction column through the elution solution¹⁸F-PSMA-BCH is flushed to obtain free¹⁸F^-Al of (2)¹⁸F-PSMA-BCH aqueous solution.

13. The method of any one of claims 10-12, wherein the precursor compound has the chemical structure: