CN208877367U - A kind of positron emitting tracer Fully automated synthesis module based on 18F-BF3 label - Google Patents
A kind of positron emitting tracer Fully automated synthesis module based on 18F-BF3 label Download PDFInfo
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Abstract
The utility model discloses a kind of positron emitting tracer Fully automated synthesis modules based on 18F-BF3 label, belong to nuclear medicine and molecular imaging field.The synthesis module includes 18F‑Ionic adsorption, purifying, elution circuit, heated reaction system, synthesizing and purifying system and the processing of product sterilization and transfer system, 18F‑Ionic adsorption, purifying, elution circuit and synthesizing and purifying system pass through pipeline respectively and connect with heated reaction system, and the processing of product sterilization and transfer system are connect by pipeline with synthesizing and purifying system, the 18F‑Ionic adsorption, purifying, elution circuit realize the 18F of micro-scale volume using syringe pump Z2, two six logical proportional valve F2, quantitative loop‑Ion leacheate precisely measures and lossless transfer.Compared with prior art, the features such as Fully automated synthesis module described in the utility model has novel design, and performance is stablized, and using flexible is convenient for safeguarding, easy to spread, is particularly suitable for the synthesis of the polypeptide positron medicine based on 18F-BF3 labelling strategies under aqueous environment.
Description
Technical field
The utility model relates to nuclear medicine and molecular imaging field, it is specifically a kind of based on 18F-BF3 label
Positron emitting tracer Fully automated synthesis module.
Background technique
Currently, clinically the most widely used PET positron medicine is 18F-FDG, but the imaging agent can only observe it is swollen
The exception of tumor glycometabolism, and there is also certain problem (cannot effectively distinguish inflammation and tumor tissues) for specificity, it is also uncomfortable
The imaging of syncerebrum portion is come out one after another to make up these insufficient many imaging agents with different role target spot, such as based on proliferation
The 18F-FLT of imaging, for the 18F-FMISO of hypoxia imaging, the 18F- ethyl tyrosine of amino acid metabolism class etc., and these
Imaging agent may be by full-automatic synthesizer (such as Tracer Lab of General Electric Company (medical system) of commercialization
FX F-N series；The Syn Chrom R&D of German Raytest company；The fluorine multifunctional synthesis module PET- of Beijing Paite Co., Ltd.
MF-2V-IV-I the preparation and its purifying of entire molecular probe) are completed, but these commercializations at present to be automatically synthesized instrument main
For be based under water-less environment 18F label.Therefore, the 18F positive electron that the automatic synthesizer of these commercializations can be prepared
Medicament categories are limited.
With the rapid development of molecular biology, tumour is in its occurrence and development process, relevant albumen, and polypeptide etc. is raw
The change of specificity can all occur for object macromolecular, these large biological molecules are compared with conventional small-molecule drug target spot to be had specifically
Strong, the high advantage of biological safety of property, for tumour early detection provide advantageous target molecule library (Jackson I M,
Scott P J H,Thompson S.Clinical Applications of Radiolabeled Peptides for PET
[C]//Seminars in Nuclear Medicine.WB Saunders,2017.).Obviously, to the 18F of these biomolecule
Label cannot directly be marked by above-mentioned labeling method, the usual method is that preparing first with automation equipment
The small molecule linking arm of 18F label contains the active function groups that can be coupled with large biological molecule on these linking arms；Secondly will
Biomolecule and these small molecule linking arms carry out secondary coupling, finally finally prepare target-probe point using HPLC purifying
Son (Richter S, Wuest F.18F-labeled peptides:the future is bright [J] .Molecules,
2014,19(12):20536-20556.).But there are the following problems for this 18F labelling strategies: 1. labeling process are cumbersome, when
Journey is longer；2. marking in two steps, overall labeling yield is lower；3. having to pass through HPLC purifying could be effectively by target-probe point
Son separation, takes time and effort.
But with the appearance of novel 18F labeling method, so as to large biological molecule, the especially probe molecule of polypeptide
18F " Last-Stage " label be possibly realized, such as 18F-BF3 labelling strategies, the 18F labeling method based on B-F key, by from
The mode of son exchange realizes 18F-The exchange of 19F in ion and boron trifluoride functional group (BF3), to complete the labeled of 18F
Journey (Liu Z, Pourghiasian M, Radtke M A, et al.An Organotrifluoroborate for Broadly
Applicable One‐Step 18F‐Labeling[J].Angewandte Chemie International Edition,
2014,53(44):11876-11880.).Such 18F labeling method has the advantage that 1. labeling process can be in aqueous solution
It carries out, is handled without stringent dried over anhydrous；2. marked product is theoretically not in the by-product of other chemical molecular forms,
" Last Stage " labelling strategies may be implemented, because label system contains only two kinds of isotope probe molecular forms of F, they it
Between chemical property, targeting potency is equivalent；3. with the signal amplification in Chemical Measurement, each BF3 has three
A F atom can theoretically obtain the 18F marked product of more high specific activity；4, flag condition it is mild (80 DEG C, pH 2-3,10-
15min), it is not necessarily to any catalyst, purification process is simple.Common label process is: first by labelled precursor solution (10-
20uL) as in reaction tube, pH value is adjusted to 2-3, secondly by micro-scale volume (50-70uL) with corresponding buffer salt solution
18F-Ion species aqueous solution moves in reaction tube, heats 15-20min, and last quenching reaction is diluted with water, product is adsorbed in
On solid-phase extraction column, finally by product ethanol elution, add normal saline dilution, crosses the positive electron that sterilised membrane filter obtains 18F label
Medicaments injection.It can be seen that the key point of such label reaction is how to realize the 18F of micro-scale volume-Ion leacheate essence
Standard measures and lossless transfer.
Currently, utilizing micropipettor hand mainly by staff based on this kind of " Last-Stage " 18F label of 18F-BF3
The dynamic 18F for completing micro-scale volume-Ion leacheate is precisely measured and is pipetted.In the case where current medication increase in demand, manual operation
The occupational exposure of staff is not only increased, and increases the risk of human error in pharmacy procedure.And existing commodity
Changing multifunction automatic synthesizer can be only used for the preparation of limited kinds 18F positron medicine, and commercialization module liquid at present
Body transfer scheme mainly passes through positive pressure of nitrogen and shifts liquid in reagent bottle, can not achieve the accurate measurement and nothing of micro-scale volume
Damage transfer, therefore be not suitable for the preparation of the novel 18F-BF3 positron medicine.
Summary of the invention
The technical assignment of the utility model is in view of the above shortcomings of the prior art, to provide a kind of based on 18F-BF3 label
Positron emitting tracer Fully automated synthesis module.The characteristics of module is for such label reaction, may be implemented to 18F-
Quick, the efficient Fully automated synthesis of BF3 polypeptide positron medicine is particularly suitable for marking under aqueous environment based on 18F-BF3
The polypeptide positron medicine of strategy, a kind of soluble small molecular amino acids and polypeptide positive electricity including the functional group containing BF3
The synthesis of sub- drug.
The technical assignment of the utility model is realized in the following manner: it is a kind of based on 18F-BF3 label positive electron put
Penetrating property drug Fully automated synthesis module, its main feature is that including 18F-Ionic adsorption, purifying, elution circuit, heated reaction system, conjunction
At purification system and the processing of product sterilization and transfer system, 18F-Ionic adsorption, purifying, elution circuit and synthesizing and purifying system
It is connect respectively by pipeline with heated reaction system, the processing of product sterilization and transfer system pass through pipeline and synthesizing and purifying system
Connection,
The 18F-Ionic adsorption, purifying, elution circuit are real using syringe pump Z2, two six logical proportional valve F2, quantitative loop
The 18F of existing micro-scale volume-Ion leacheate precisely measures and lossless transfer.
Preferably, the 18F-Ionic adsorption, purifying, elution circuit is mainly by syringe pump Z2, two six logical proportional valves
F2, quantitative loop, two-bit triplet solenoid valve V21, two-bit triplet solenoid valve V22, two-bit triplet solenoid valve V23, two-bit triplet electromagnetism
Valve V24, miniature QMA column, H2 18O returnable bottle, 18F-Ion leacheate bottle is constituted, and syringe pump Z2, two six logical proportional valve F2, is determined
Amount ring, two-bit triplet solenoid valve V21, two-bit triplet solenoid valve V22 are connected, for drawing the 18F of fixed body accumulated amount-Ion leaching
Washing lotion；Syringe pump Z2, two-bit triplet solenoid valve V21, two-bit triplet solenoid valve V22, two six logical proportional valve F2, quantitative loop, two
Position-3-way solenoid valve V23, miniature QMA column, two-bit triplet solenoid valve V24 are connected, and are used for 18F-Ion elution is anti-to heating
It answers in system；H2 18O returnable bottle is connected to two-bit triplet solenoid valve V23, for recycling H2 18O；18F-Ion leacheate bottle and two
The logical proportional valve F2 connection in position six, for providing leacheate；Two-bit triplet solenoid valve V24 meets target water inlet pipe pipeline connector G1.
The synthesizing and purifying system is mainly by syringe pump Z1, a logical N switching valve F1, solid-phase extraction column 52, two-bit triplet electricity
Magnet valve V11, two-bit triplet solenoid valve V12, several reagent bottles 1 and waste liquid bottle are constituted, and N is oneself more than or equal to 6, less than or equal to 10
So number, preferably 6,8 or 10, syringe pump Z1 by a logical N switching valve F1 and each reagent bottle 1, heated reaction system, product without
Bacteriumization processing and transfer system connection, syringe pump Z1 also passes through a logical N switching valve F1, two-bit triplet solenoid valve V11 connects solid phase extraction
Column one end is taken, the solid-phase extraction column other end connects waste liquid bottle by two-bit triplet solenoid valve V12 and product sterilization handles and transfer
System.
In order to preferably adapt to the Fully automated synthesis based on the 18F-BF3 positron emitting tracer marked, a logical N
Switching valve F1 is connected by pipeline with 2-5 reagent bottle, and each reagent bottle is respectively used to hold medicinal alcohol, water for injection, production
Product leacheate and/or physiological saline etc..
The filler of solid-phase extraction column is preferably C18, HLB or neutral alumina.
Preferably, the heated reaction system is mainly made of reaction tube, temperature control heating device, reaction tube and 18F-From
Son absorption, purifies, and the two-bit triplet solenoid valve V24 in elution circuit, the logical N switching valve F1 in synthesizing and purifying system are connected
Logical, temperature control heating device is used to heat the reaction medium in reaction tube.
For the ease of controlling heating time, the heated reaction system can also include elevating mechanism, the elevating mechanism
For driving temperature control heating device to go up and down, to change reaction tube at a distance from temperature control heating device heating region.
The reaction tube is preferably able to bear the plastic material of 150 DEG C of high temperature, and bottom is preferably taper.
The heating device preferably uses the temperature control system based on pid algorithm, and temperature control precision is less than or equal to ± 1
℃。
The elevating mechanism can be used in the prior art any one can be realized temperature control heating device lifting machinery, gas
Dynamic, electric structure, for example, entire temperature control heating device is recycled the bands such as stepper motor, screw rod as on stepper motor slide unit
Dynamic stepper motor slide unit moves up and down.
Preferably, the product sterilization processing and transfer system are mainly by rolling bottle, production in negative pressure control, product
Product receiving flask and sterilised membrane filter are constituted, and negative pressure control is used to provide negative pressure for product receiving flask, and product receiving flask passes through nothing
Bacterium filter membrane is practiced midwifery rolling bottle in product, and rolling bottle passes through a logical N switching valve F1, the two-bit triplet in pipeline and synthesizing and purifying system in product
Solenoid valve V12 is connected.
Waste liquid bottle of the negative pressure control also for synthesizing and purifying system provides negative pressure, in order to pass through negative pressure for Solid Phase Extraction
Remaining waste liquid is transferred in waste liquid bottle in column.
Negative pressure control described in the utility model can be made of vacuum diaphragm pump and draft regulator, by receiving product
Collect bottle and maintains constant negative pressure.
The control mode of the utility model Fully automated synthesis module includes by the complete of programmable logic controller (PLC) (PLC) control
Automatic control mode, segmented semiautomatic control mode and MANUAL CONTROL mode.
The positron emitting tracer Fully automated synthesis module and the prior art based on 18F-BF3 label of the utility model
Compared to following prominent the utility model has the advantages that
(1) liquid quantifies, and constant speed transfer is realized mainly by syringe pump driven by stepper motors, by with it is corresponding
Valve combine, accurate quantitative, constant speed of the liquid in respective line, orientation transfer may be implemented, more conventional positive pressure of nitrogen shifts
The scheme controllability of liquid is good；
(2) innovative that two six logical proportional valves are utilized, different volumes can be replaced according to specific embodiment
Quantitative loop may be implemented to 18F-Ion elution volume is precisely controlled, the label system particularly suitable for micro-scale volume；
(3) flowing of liquid in the module is mainly by stepper motor driven syringe pump, and by vacuum diaphragm pump and negative pressure
The negative pressure control of adjuster composition, thus eliminates the use of high-pressure nitrogen bottle, eliminates the fiber crops of nitrogen pipeline wiring
It is tired；
(4) it is the temperature control system based on pid algorithm that heating device is adoptable, has the advantages that temperature control is accurate；And it is entire
Heating device is fixed on elevating mechanism, can be by up and down adjustment position, whether realizing the heating to reaction tube.
It can first heat up to it before reaction tube heats, when reaction tube needs to heat, directly rise to corresponding positions
It sets and reaction tube is heated, the time of heat temperature raising can be saved, shorten the generated time of positron medicine；
(5) reaction tube is the plastic material that can bear 150 DEG C of high temperature, and bottom is taper.More typical glass material
Reaction tube chemical inertness is high, can reduce in acid condition reaction tube to 18F-The absorption of ion.
Detailed description of the invention
Attached drawing 1 is the structure of the positron emitting tracer Fully automated synthesis module based on 18F-BF3 label in embodiment
Schematic diagram.
In figure, 11, reagent bottle (spare)；12, reagent bottle (0.9% physiological saline)；13, reagent bottle (product leacheate)；
14, reagent bottle (75% medicinal alcohol)；15, reagent bottle (sterile water for injection)；21,18F-(0.9% is raw for ion leacheate bottle
Manage salt water, pH=2.0)；22,H2 18O returnable bottle；23, reaction tube；24, quantitative loop；31, waste liquid bottle；32, rolling bottle in product；33,
Product receiving flask；34,0.22uM sterilised membrane filter；41, stepper motor；42, temperature control heating device；43, negative pressure adjusting controller；
44, vacuum diaphragm pump；45, slide unit；51, miniature QMA column；52, C18 solid-phase extraction column；Z1 is syringe pump, range 20mL；Z2
For syringe pump, range 5mL；F1 is logical ten switching valves；F2 is two six logical proportional valves；V11,V12,V21,V22,V23,
V24 is two-bit triplet solenoid valve；V31, V32, V34 are 2/2-way solenoid valve.
Attached drawing 2 is that the radioactivity of positron medicine prepared by module before purification is automatically synthesized with drug described in embodiment one
HPLC chromatogram.
Attached drawing 3 is that the sterile product after purification of positron medicine prepared by module is automatically synthesized with drug described in embodiment one
The radioactivity HPLC chromatogram of liquid.
Attached drawing 4 is the 19F reference substance purple that positron medicine prepared by module is automatically synthesized with drug described in embodiment one
Outer visible HPLC chromatogram.
Specific embodiment
Referring to Figure of description with specific embodiment to the positron radioactivity based on 18F-BF3 label of the utility model
Drug Fully automated synthesis module is described in detail below.
Unless otherwise instructed, the content of following each ingredients used is weight percentage content.
Embodiment:
As shown in Fig. 1, the positron emitting tracer Fully automated synthesis mould based on 18F-BF3 label of the utility model
Block is mainly by 18F-Ionic adsorption, purifying, elution circuit, heated reaction system, synthesizing and purifying system and the processing of product sterilization
And transfer system composition.
The 18F-Ionic adsorption, purifying, elution circuit is mainly by syringe pump Z2, two six logical proportional valve F2, quantitative loop
24, two-bit triplet solenoid valve V21, two-bit triplet solenoid valve V22, two-bit triplet solenoid valve V23, two-bit triplet solenoid valve V24, micro-
Type QMA column 51,18F-Ion leacheate bottle 21, H2 18O returnable bottle 22 is constituted.
The upper and lower ends of quantitative loop 24 are connect with 1, No. 4 channel of two six logical proportional valve F2 respectively.Two six logical quantitative
No. 2 channels of valve F2 meet syringe pump Z2 by two-bit triplet solenoid valve V22, two-bit triplet solenoid valve V21, and No. 2 channels also pass through
Two-bit triplet solenoid valve V22 connects No. 6 channels.No. 3 channels of two six logical proportional valve F2 meet 18F by pipeline-Ion leacheate
Bottle 21；No. 5 channels connect reaction tube 23 by two-bit triplet solenoid valve V23, miniature QMA column 51, two-bit triplet solenoid valve V24.Two
Position-3-way solenoid valve V24 also passes through pipeline and meets target water inlet pipe pipeline connector G1.Two-bit triplet solenoid valve V23 meets H by pipeline2 18O
Returnable bottle 22.The vacant end channel of two-bit triplet solenoid valve V21 connects atmosphere.
Draw 18F-When ion leacheate, by two-bit triplet solenoid valve V21, two-bit triplet solenoid valve V22, two six logical fixed
Measure No. 2 channels of valve F2 (being now in 1), No. 1 channel, quantitative loop 24, two six logical proportional valve F2 (being now in 1)
No. 4 channels, No. 3 channels, 18F-Ion leacheate bottle 21 is connected, and quantitative loop 24 is full of leacheate using syringe pump Z2.It draws
After the completion of operation, two-bit triplet solenoid valve V22 is opened, successively by two-bit triplet solenoid valve V21, two-bit triplet solenoid valve V22, two
No. 6 channels of six logical proportional valve F2 (being now in 2) of position, No. 1 channel, quantitative loop 24, two six logical proportional valve F2 (locate at this time
In 2) No. 4 channels, No. 5 channels, two-bit triplet solenoid valve V23, miniature QMA column 51, two-bit triplet solenoid valve V24, reaction
Pipe 23 is connected, and leacheate in quantitative loop 24 can be made to slow transit through miniature QMA column 51, and final elution is into reaction tube 23.
The synthesizing and purifying system is mainly by syringe pump Z1, a logical ten switching valve F1, C18 solid-phase extraction column 52, two three
Three-way electromagnetic valve V11, two-bit triplet solenoid valve V12, reagent bottle 11, reagent bottle 12, reagent bottle 13, reagent bottle 14, reagent bottle 15 and
Waste liquid bottle 31 is constituted.No. 1 channel of one logical ten switching valve F1 connects atmosphere；No. 2 channels connect reaction tube 23；No. 3 channels pass through two
Three-way magnetic valve V11, C18 solid-phase extraction column 52, two-bit triplet solenoid valve V12 connect waste liquid bottle 31, rolling bottle 32 in product；No. 5 logical
Road is practiced midwifery rolling bottle 32 in product；No. 6 channels, No. 7 channels, No. 8 channels, No. 9 channels, No. 10 channels pass through pipeline and reagent bottle respectively
11, reagent bottle 12, reagent bottle 13, reagent bottle 14, reagent bottle 15 connect.The vacant end channel of two-bit triplet solenoid valve V11 connects greatly
Gas.
The product leacheate in a certain amount of reagent bottle 13 is drawn by syringe pump Z1, then passes through a logical ten switching valve F1's
No. 3 channels, through two-bit triplet solenoid valve V11 by product from being eluted on C18 solid-phase extraction column 52 in product in rolling bottle 32.Then
The physiological saline in a certain amount of reagent bottle 12 is drawn by syringe pump Z1, No. 5 channels of ten switching valve F1 of Jing Yitong will be in product
Product liquid in rolling bottle 32 is diluted.
The heated reaction system is mainly by reaction tube 23, stepper motor 41, temperature control heating device 42, stepper motor slide unit
45 are constituted.Reaction tube 23 is made of the plastic material for being able to bear 150 DEG C of high temperature, and bottom is taper.Temperature control heating device
The shape of 42 heating regions can be adapted with reaction tube 23, and using the temperature control system based on pid algorithm, temperature-controlled precision is small
In equal to ± 1 DEG C.Temperature control heating device 42 is fixed on stepper motor slide unit 45, and drives stepper motor using stepper motor 41
Slide unit 45 moves up and down.
Preferably, the product liquid sterilization processing and transfer system are mainly by vacuum diaphragm pump 44, draft regulator
43, rolling bottle 32, product receiving flask 33 and sterilised membrane filter 34 are constituted in product.Negative pressure control be used for for product receiving flask 33,
Waste liquid bottle 31 provides negative pressure.Product receiving flask 33 is practiced midwifery rolling bottle 32 in product by sterilised membrane filter 34.
The control program of above-mentioned Fully automated synthesis module can be write based on programmable logic controller (PLC) (PLC).It prepares each
Kind of positron medicine have one it is specific execute file, and the execution file can by encryption to program carry out protection and
The opening of editing authority.After the program editted is written to PLC, full automatic control, hand can be realized by outer button
Dynamic control, segmented semiautomatic control.
For synthesizing 18F-AMBF3-C (RGDfK) drug, radioactivity medicine is prepared to using above-mentioned Fully automated synthesis module
The operating process of object provides following explanation:
Need to be put into sterile water for injection 30mL before the synthesis in reagent bottle 15, reagent bottle 14 is put into 75% medical wine
Smart 40mL is put into 80% ethanol water 10mL in reagent bottle 13,0.9% physiological saline is put into reagent bottle 12 (for diluting
Product liquid) 20mL, 0.9% physiological saline (pH=2.0, for eluting 18F is put into reagent bottle 21-Ion is to reaction tube)
10mL activates C18 solid-phase extraction column 52, activates miniature QMA column 51.A certain amount of labelled precursor solution is added in reaction tube 23 in advance
The buffer salt solution (1M, 5uL, pH=2.0) of (10mM, 10uL), certain volume amount are spare.
1. detergent line: before formally starting synthesis, needing all pipelines to equipment, rolling bottle 32 in product, reaction tube
23 are cleaned.
1.1 75% medicinal alcohol: a logical ten switching valve F1 are switched into No. 9 channels, syringe pump Z1 is with 20mL/min's
Speed is drawn the medicinal alcohol of 16mL 75% by bottle 14, and a logical ten switching valve F1 are switched to No. 2 channels, inject 4mL to reaction
Pipe 23；A logical ten switching valve F1 are then switched into No. 3 positions, inject 4mL to waste liquid bottle 31；Then two-bit triplet solenoid valve is opened
V12 injects rolling bottle 32 into product 4mL；One logical ten switching valve F1 are switched into No. 5 channels, inject 4mL rolling bottle into product
32。
The cleaning of 1.2 waters for injection: logical ten switching valves are then switched into No. 10 channels, syringe pump Z1 is with 20mL/min's
Speed draws 16mL water for injection, similarly to elute sequence, cleans to pipeline.
1.3 all pipelines of drying: logical ten switching valves are then switched into No. 1 channel (and atmosphere communicates), syringe pump Z1
16mL air is drawn with the speed of 20mL/min, similarly to elute sequence, dries up all pipelines.
1.4 installation purification columns, reaction tube: miniature QMA column 51 is connected to two-bit triplet solenoid valve V23, two-bit triplet electromagnetism
Between valve V24；By C18 solid-phase extraction column 52 connect with two-bit triplet solenoid valve V11, between two-bit triplet solenoid valve V12；It will be equipped with
Reaction tube used in detergent line on the reaction tube replacement equipment of precursor.
2. 18F-The production of ion: 18O (p, n) 18F nuclear reaction, GE Minitrace medical cyclotron are used
(30uA, 20-40min) bombardment is equipped with H2 18The target body of O (97%, 2.0mL), then will contain 18F with He gas-The target water of ion
It is transferred to through target water inlet pipe pipeline connector G1, two-bit triplet solenoid valve V24, miniature QMA column 51, two-bit triplet solenoid valve V23
H2 18In O returnable bottle 22, entire pipeline and miniature QMA column 51 persistently are done with He air-blowing.
3. 18F-Elution and transfer: first by two six logical proportional valve F2 be placed in 1 (channel 1-2 connect, channel 3-4
Connect, channel 5-6 is connected), with syringe pump Z2 by 18F-18F is drawn in ion leacheate bottle 21-Ion leacheate is by quantitative loop 24
(50uL) is full of；Then two six logical proportional valve F2 being placed in 2, (channel 6-1 is connected, and channel 2-3 is connected, and channel 4-5 connects
It is logical), extra leacheate is returned into 18F-In ion leacheate bottle 21；Two-bit triplet solenoid valve V21 is then turned on to draw centainly
The air of amount closes two-bit triplet solenoid valve V21, opens two-bit triplet solenoid valve V22, two six logical proportional valves are placed in 2,
Two-bit triplet solenoid valve V23, two-bit triplet solenoid valve V24 are opened simultaneously, Z2 is pumped with 4mL/min speed bolus infusion, it is quantitative
Channel 5 of the leacheate through two six logical proportional valve F2 in ring 24, two-bit triplet solenoid valve V23, miniature QMA column 51, two three
Three-way electromagnetic valve V24, eventually enters into reaction tube.
4. 18F-Ion is marked with precursor 19F-AMBF3-C (RGDfK): will have been heated to preset temperature in advance
The temperature control heating device 42 of (85 DEG C) is risen at reaction tube 23 using stepper motor 41, begins to warm up 15min, after heating,
Temperature control heating device 42 declines, the cooling 5min of reaction tube 23.
5. purifying products:
5.1 product hanging columns: cutting F1 for logical ten switching valves and shift to No. 10 channels, syringe pump Z1 with the speed of 20mL/min from
15mL water for injection is drawn in bottle 15, is then switched to No. 2 positions, 15mL water for injection is transferred to reaction tube with identical speed
In 23, reaction system is diluted, dilution will be then drawn in syringe pump Z1 with the speed communicated.By logical ten switching valves
It cuts F1 and shifts to No. 3 channels, by the reaction solution after dilution through two-bit triplet solenoid valve V11, C18 solid-phase extraction column 52, two-bit triplet
Solenoid valve V12 is injected in waste liquid bottle 31 with the speed of 7mL/min, and finally product is adsorbed on C18 solid-phase extraction column 52.
5.2 flushing C18 solid-phase extraction columns 52: a logical ten switching valve F1 are switched into No. 10 channels, syringe pump Z1 is with 20mL/
The speed of min draws 5mL water for injection from reagent bottle 15, is then switched to No. 3 positions, through two-bit triplet solenoid valve V11, C18
Solid-phase extraction column 52, two-bit triplet solenoid valve V12 rinse C18 solid-phase extraction column 52 with the speed water for injection of 7mL/min and arrive
In waste liquid bottle 31, by 18F unlabelled on C18 solid-phase extraction column 52-Ion washes away.
5.3 drying C18 solid-phase extraction columns 52: open two-bit triplet solenoid valve V11, make 52 one end of C18 solid-phase extraction column with
Atmosphere communicates, and the other end is connected by two-bit triplet solenoid valve V12 with waste liquid bottle 31, opens two-bit triplet solenoid valve V32, starting
Vacuum pump 44 and draft regulator 43 make the negative pressure a that -70Kpa is formed in waste liquid bottle 31, by negative pressure by C18 Solid Phase Extraction
Remaining water is transferred in waste liquid bottle 31 in column 52.
6. product is eluted to middle rolling bottle 32: a logical ten switching valve F1 being switched to No. 8 channels, syringe pump Z1 is with 4mL/min
Speed by drawing 1mL product leacheate in bottle 13, a logical ten switching valve F1 are then switched into No. 3 positions, open two-bit triplet
Solenoid valve V12, through two-bit triplet solenoid valve V11, C18 solid-phase extraction column 52, two-bit triplet solenoid valve V12, with product leacheate
The product adsorbed on solid-phase extraction column 52 is eluted into (elution speed 4mL/min), product is finally transferred to rolling bottle in product
In 32.
7. cut-back product liquid: a logical ten switching valve F1 are switched into No. 7 channels, syringe pump Z1 with the speed of 20mL/min by
0.9% physiological saline of 5mL is drawn in bottle 12, a logical ten switching valve F1 are then switched into No. 5 positions, with identical speed by 0.9%
Physiological saline is injected in product in rolling bottle 32.
8. being transferred to product receiving flask 33: after mixing to liquid in rolling bottle in product, opening two-bit triplet solenoid valve
V31 starts vacuum pump 44 and draft regulator 43, makes the negative pressure that will form-a 40Kpa in product receiving flask 33, product liquid
It will be transferred to by sterilised membrane filter 34 by rolling bottle 32 in product spare in product receiving flask 33.
Obviously, the above embodiments are merely examples for clarifying the description, and does not limit the embodiments.It is right
For those of ordinary skill in the art, can also make on the basis of the above description other it is various forms of variation or
Person changes.There is no necessity and possibility to exhaust all the enbodiments.And thus amplify out it is obvious variation or
Person changes among the protection scope created still in the utility model.
Claims (9)
1. a kind of positron emitting tracer Fully automated synthesis module based on 18F-BF3 label, it is characterised in that: including 18F-
Ionic adsorption, purifying, elution circuit, heated reaction system, synthesizing and purifying system and the processing of product sterilization and transfer system,
18F-Ionic adsorption, purifying, elution circuit and synthesizing and purifying system pass through pipeline respectively and connect with heated reaction system, product without
Bacteriumization processing and transfer system are connect by pipeline with synthesizing and purifying system,
The 18F-Ionic adsorption, purifying, elution circuit are realized micro using syringe pump Z2, two six logical proportional valve F2, quantitative loop
The 18F of volume-Ion leacheate precisely measures and lossless transfer.
2. the positron emitting tracer Fully automated synthesis module according to claim 1 based on 18F-BF3 label, special
Sign is: the 18F-Ionic adsorption, purifying, elution circuit mainly by syringe pump Z2, two six logical proportional valve F2, quantitative loop,
It is two-bit triplet solenoid valve V21, two-bit triplet solenoid valve V22, two-bit triplet solenoid valve V23, two-bit triplet solenoid valve V24, miniature
QMA column, H2 18O returnable bottle, 18F-Ion leacheate bottle is constituted, syringe pump Z2, two six logical proportional valve F2, quantitative loop, two three
Three-way electromagnetic valve V21, two-bit triplet solenoid valve V22 are connected, for drawing the 18F of fixed body accumulated amount-Ion leacheate；Syringe pump
Z2, two-bit triplet solenoid valve V21, two-bit triplet solenoid valve V22, two six logical proportional valve F2, quantitative loop, two-bit triplet solenoid valve
V23, miniature QMA column, two-bit triplet solenoid valve V24 are connected, and are used for 18F-Ion is eluted into heated reaction system；H2 18O
Returnable bottle is connected to two-bit triplet solenoid valve V23, for recycling H2 18O；18F-Ion leacheate bottle and two six logical proportional valve F2
Connection, for providing leacheate；Two-bit triplet solenoid valve V24 meets target water inlet pipe pipeline connector G1.
3. the positron emitting tracer Fully automated synthesis module according to claim 1 or 2 based on 18F-BF3 label,
It is characterized by: the synthesizing and purifying system is mainly by syringe pump Z1, a logical N switching valve F1, solid-phase extraction column, two-bit triplet electricity
Magnet valve V11, two-bit triplet solenoid valve V12, several reagent bottles and waste liquid bottle are constituted, and N is oneself more than or equal to 6, less than or equal to 10
So number,
Syringe pump Z1 passes through a logical N switching valve F1 and each reagent bottle, heated reaction system, the processing of product sterilization and transfer system
Connection, syringe pump Z1 also passes through a logical N switching valve F1, two-bit triplet solenoid valve V11 connects solid-phase extraction column one end, solid-phase extraction column
The other end connects waste liquid bottle and the processing of product sterilization and transfer system by two-bit triplet solenoid valve V12.
4. the positron emitting tracer Fully automated synthesis module according to claim 3 based on 18F-BF3 label, special
Sign is: a logical N switching valve F1 is connected by pipeline with 2-5 reagent bottle.
5. the positron emitting tracer Fully automated synthesis module according to claim 3 based on 18F-BF3 label, special
Sign is: the filler of solid-phase extraction column is C18, HLB or neutral alumina.
6. the positron emitting tracer Fully automated synthesis module according to claim 3 based on 18F-BF3 label, special
Sign is: the heated reaction system is mainly made of reaction tube, temperature control heating device, reaction tube and 18F-Ionic adsorption, it is pure
Change, two-bit triplet solenoid valve V24, the logical N switching valve F1 in synthesizing and purifying system in elution circuit are connected, temperature control heating
Device is used to heat the reaction medium in reaction tube.
7. the positron emitting tracer Fully automated synthesis module according to claim 6 based on 18F-BF3 label, special
Sign is: the heated reaction system further includes elevating mechanism, and the elevating mechanism is used to that temperature control heating device to be driven to go up and down, with
Change reaction tube at a distance from temperature control heating device heating region.
8. the positron emitting tracer Fully automated synthesis module according to claim 6 based on 18F-BF3 label, special
Sign is: product sterilization processing and transfer system mainly by rolling bottle in negative pressure control, product, product receiving flask and
Sterilised membrane filter is constituted, and negative pressure control is used to provide negative pressure for product receiving flask, and product receiving flask is practiced midwifery by sterilised membrane filter
Rolling bottle in product, rolling bottle passes through a logical N switching valve F1, the two-bit triplet solenoid valve V12 in pipeline and synthesizing and purifying system in product
It is connected.
9. the positron emitting tracer Fully automated synthesis module according to claim 8 based on 18F-BF3 label, special
Sign is: waste liquid bottle of the negative pressure control also for synthesizing and purifying system provides negative pressure.
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| CN113019279A (en) * | 2021-03-11 | 2021-06-25 | 山西医科大学第一医院 | Automatic synthesis device for preparing radiopharmaceuticals and using method thereof |
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