CN106749435A - A kind of Novel PET probe synthesis system - Google Patents
A kind of Novel PET probe synthesis system Download PDFInfo
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- CN106749435A CN106749435A CN201611088904.XA CN201611088904A CN106749435A CN 106749435 A CN106749435 A CN 106749435A CN 201611088904 A CN201611088904 A CN 201611088904A CN 106749435 A CN106749435 A CN 106749435A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0491—Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
Abstract
The invention discloses a kind of Novel PET probe synthesis system, the system includes that some PET probes synthetic towers, half prepare HPLC, Rotary Evaporators, and wash-out magnetic valve and some solid-phase extraction columns, isotopic ion enters solid-phase extraction column through eluting magnetic valve, SPE column outlet is connected with synthetic tower, the product synthesized in PET probe synthetic towers enters half preparation HPLC after solid-phase extraction column preliminary purification and is further purified, and Rotary Evaporators evaporation solution concentration is entered afterwards and obtains PET probes.The system can be according to the number and connected mode of PET probe synthetic towers in synthesis purpose voluntarily selection system, it is possible to achieve be related to the probe of a step or multistep reaction to synthesize, highly versatile.
Description
Technical field
The present invention relates to a kind of probe synthesizer, more particularly to a kind of Novel PET probe synthesis system, the system can be square
Just various PET probes are synthesized.
Background technology
PET is the New video that biomolecule metabolism, acceptor and neurotransmitter activity can be shown on live body only at present
Technology, has been widely used in the Diagnosis and differential diaggnosis of various diseases, state of an illness judgement, therapeutic evaluation, organ function research and new
The aspects such as medicine exploitation.Not only sensitivity is high for PET, and specificity is high, and security is good, and it can be disposably complete with total body opacification, PET
Body imaging checks the image that just can obtain whole body regional.PET is a kind of imaging for reflecting molecule metabolism, at disease early stage
In molecular level changes phase, the morphosis of diseased region is not yet presented exception, when MRI, CT examination can't clarify a diagnosis,
PET is checked can find focus place, and can obtain 3-dimensional image, moreover it is possible to carry out quantitative analysis, reach early diagnosis, this is mesh
Preceding other image checks are incomparable.
PET probes are also referred to as after PET developers are guided in vivo carrying out the radioactivity medicine of internal organs, tissue or molecular imaging
Thing.After radiopharmaceutical is introduced in vivo, dense can gather in target organ or tissue, the ray launched it by imaging instrument is carried out
Detection, so as to obtain medicine distributed image in vivo, is used to diagnose various diseases.The usual type of PET probes has：Glucose
The fluoro- deoxyglucose of class, such as 18- is most common pet imaging agent, accounts for 90%；Blood flow class, such as 13- nitrogen-ammoniacal liquor, 15- oxygen-
Water, 85- rubidiums can be used for regional myocardial blood flow's perfusion imaging；Amino acids such as 11- carbon-methionine, 18- fluoro-2-methyl tyrosine,
The fluoro- ethyl tyrosine of 18-, is mainly used in diagnosing tumor and antidiastole；Nucleotides developer, the fluoro- Brdurds of 18- are used
In study tumor cell division growth, to assess drug effect and antidiastole；Acceptor class etc..Common synthetic instrument is often special synthesis
PET probes are determined, so one can conveniently synthesize various PET probes and have great practical value.
The content of the invention
The purpose of the present invention is to solve the shortcomings of the prior art, there is provided a kind of Novel PET probe synthesis of highly versatile
System, the system can synthesize the PET probes of a step or multistep reaction, and highly versatile can preferably study PET probes and exist
Application in terms of imaging.
Novel PET probe synthesis system of the invention, including some PET probes synthetic towers, half prepare HPLC, rotation and steam
Hair instrument；Every PET probes synthetic tower includes synthetic tower main body and controller, and described synthetic tower main body includes going up from top to bottom
Lower movable upper tray, the fixed plate for fixing reaction bulb and lower tray moving up and down, in synthetic tower master
Some three-way magnetic valves are additionally provided with body, controller is used to control upper tray, the motion of lower tray and three-way magnetic valve
Break-make；Half described preparation HPLC includes a radioactivity seeker, is installed in half preparation HPLC after UV detectors；Should
Synthesis system also includes wash-out magnetic valve and some solid-phase extraction columns, and isotopic ion enters SPE through eluting magnetic valve
Post, SPE column outlet is connected with a certain three-way magnetic valve on synthetic tower, and the product synthesized in PET probe synthetic towers is through solid phase
Enter half preparation HPLC after extraction column preliminary purification to be further purified, Rotary Evaporators evaporation solution concentration is entered afterwards and is obtained
PET probes.
In above-mentioned technical proposal, the up and down motion of described synthetic tower main body middle and upper part column plate, move forward and backward and lower tower
The up and down motion of plate drives screw drive to realize by motor.
Described Rotary Evaporators include external control box, the lifting for controlling direction of rotation and speed and water-bath
And bath temperature.
Can be according to the number and connected mode of PET probe synthetic towers in synthesis purpose voluntarily selection system when using, can
To realize being related to the probe of a step or multistep reaction to synthesize, the present invention is to be capable of achieving the conjunction of various probes using set of system
Into versatility is extremely strong.
Brief description of the drawings
Fig. 1 is the structure annexation schematic diagram of synthesis system of the present invention.
Fig. 2 is the present the most frequently used PET probes of synthesis18The operational flowchart of F-FDG.
Fig. 3 is the PET probes of composite diagnosis senile dementia18The process flow diagram flow chart of F-T807.
Fig. 4 is the structural representation of synthetic tower main body, and 1 is three-way magnetic valve in figure, and 2 is terminal box, and 3 is upper tray, 4
It is fixed plate, 5 is lower tray, and 6 is motor.
Specific embodiment
The present invention will be further described with instantiation below in conjunction with the accompanying drawings.
Novel PET probe synthesis system of the invention, including some PET probes synthetic towers, half prepare HPLC, rotation and steam
Hair instrument；PET probe synthetic towers are mainly used in carrying out synthetic reaction, and half prepares HPLC is used to purify synthetic product, rotates
Evaporimeter is used to concentrate product；Every PET probes synthetic tower includes synthetic tower main body and controller, is illustrated in figure 3 synthesis
The general structure schematic diagram of tower main body, synthetic tower main body from top to bottom include can move forward and backward up and down upper tray 3, for consolidate
Determine the fixed plate 4 and lower tray moving up and down 5 of reaction bulb, some threeway electromagnetism are additionally provided with synthetic tower main body
Valve 1, controller is used to control the break-make of upper tray, the motion of lower tray and three-way magnetic valve；Half described preparation HPLC
Including a radioactivity seeker, it is installed in half preparation HPLC after UV detectors, product preferably can be entered into traveling one
Step purifying；The synthesis system also includes wash-out magnetic valve and some solid-phase extraction columns, and described wash-out magnetic valve can be by 2 groups of pipes
Road is constituted, and 2 enter 2 goes out, and can be entered by isotopic ion by 1 group of pipeline, waste liquid outflow, then by another 1 group of pipeline by drip washing
Liquid enters, and is eluted on anion-exchange column18F ion or other isotopic ions, eluent are imported in reaction bulb, are such as schemed
Shown in 1, isotopic ion enters solid-phase extraction column, a certain three energization with synthetic tower of SPE column outlet through eluting magnetic valve
Magnet valve is connected, and it is further that the product synthesized in PET probe synthetic towers enters half preparation HPLC after solid-phase extraction column preliminary purification
Purifying, enters Rotary Evaporators evaporation solution concentration and obtains PET probes afterwards.
In above-mentioned technical proposal, the up and down motion of described synthetic tower main body middle and upper part column plate, move forward and backward and lower tower
The up and down motion of plate respectively drives screw drive to realize by motor, and screw rod will be driven to rotate when the motor is energized, so that
The movement of control tower can respectively be driven.
Described Rotary Evaporators also include external control box, the liter for controlling direction of rotation and speed and water-bath
Drop and bath temperature, Rotary Evaporators are mainly used in the concentration of product, and the product of subsequent treatment directly enters rotation and revolves by conduit
Turn the revolving bottle in evaporimeter, derived by conduit again after concentration, revolving bottle is 19/24 mouthful of pear-shaped flask of standard, by right
Common Rotary Evaporators are improved, and face is remotely grasped outside thermal synthesis room to add external control box to cause all operations
Make, it is to avoid the influence of radioactive material confrontation health.
The three-way magnetic valve of the control liquid flowing, corresponding interface is all standard interface, so being easy to
It is connected with pipeline.
The system can be real according to the number and connected mode of PET probe synthetic towers in synthesis purpose voluntarily selection system
Now refer to the probe synthesis of a step or multistep reaction.
To synthesize the most frequently used PET probes now18As a example by F-FDG (deoxyribose of fluorine 18)：Because synthesis18F-FDG only needs one
Step substitution reaction (hydrolysis is carried out in solid phase column), so only needing to a synthetic tower, fixed plate is fixed on by reaction bulb
On, heater is located on lower tray, and three-way magnetic valve one end connection SPE column outlet, an one end import on synthetic tower
Reaction bulb, other end connection N2, by solid phase column18The purity of F-FDG has been able to reach requirement, it is possible to without follow-up
Half preparation HPLC purifying and rotary evaporation concentration, as shown in Fig. 2 detailed process can be as follows：Produced by cyclotron18F ion target water customization pig bottle be transferred to synthesis hot cell in, pushing syringe 1 make air will customize pig bottle in18F
Solion is pressed into QMA anion-exchange columns, now18F ion will be adsorbed on QMA anion-exchange columns, and remaining liquid will
Waste liquid bottle can be entered, another road path is opened by eluting magnetic valve V1, promote the syringe 2 of dress eluent, pass through eluent
QMA anion-exchange columns are crossed, above wash-out QMA anion-exchange columns18F ion, into reaction bulb, then by synthetic tower control
Device adjustment heating oil bath processed and the position of reaction bulb, heat, to reaction bulb while being passed through N2Bubbling, in removing reaction bulb
Water, after evaporating water, promotes the syringe 3 equipped with mannose triflate acetonitrile solution liquid is entered reaction bulb, suitable
At a temperature of, nucleophilic fluorination reaction is carried out, after question response terminates, close logical N2Conduit, reacted material is transferred to transfer
Bottle, then promotes the syringe 4 equipped with NaOH solution to make reacted substance undergoes hydrolysis, solution is passed sequentially through oxidation afterwards
Aluminium post and C18 posts, product is purified, and final product is returned in the reaction bulb in pig.
To synthesize18(a kind of probe that can be combined with Tau protein-specifics, can be used for senile dementia to F-T807
Early diagnosis) as a example by：18F-T807 is to be currently used for senile dementia to early diagnose a kind of more popular probe, with reference to Fig. 3,
Synthesize with apparatus of the present invention18F-T807.In Fig. 3, the SPE of first time is completed with wash-out magnetic valve, azeotropic drying
Completed on synthetic tower with Radio-synthesis, second and third SPE is completed with three-way magnetic valve, purifying is prepared with half
HPLC is completed, and concentration is completed with Rotary Evaporators, and the addition of solution and reactant is completed with similar to the syringe in Fig. 2,
And bubbling and add the liquid drained with nitrogen after solution in pipeline in the reaction with nitrogen.Specifically synthesize：18F from
Son absorption after first solid-phase extraction column (QMA posts), with A1 leacheate drip washing solid-phase extraction columns after,18F ion is with pouring
In the reaction bulb that washing lotion enters above synthetic tower；Respectively twice plus A2 anhydrous acetonitriles and A4 anhydrous acetonitriles are in reaction bulb, carry out
Azeotropic drying, it is ensured that water is thoroughly gone out；Being subsequently adding A3DMSO+NPPI (precursor of T807) carries out Radio-synthesis, now
Temperature and reaction time are controlled by the oil bath above synthetic tower；After the completion of radioactivity necleophilic reaction, A5 water is added to carry out
After dilution, by solid-phase extraction column (C18), reacted product is allowed to adsorb face on a cl 8 column；A6 absolute ethyl alcohols are subsequently adding,
Allow absorption material to be on a cl 8 column desorbed, then purified through more than half preparation HPLC, then again pass by C18 posts and be further purified,
C18 posts are eluted with C3 absolute ethyl alcohols, then entered Rotary Evaporators concentration, then enter piping to enter into pig bottle.
Summary18F-FDG、18The synthesis of F-T807, this set system, can be with synthesis mode and associated conduit connection
According to related synthesis step, it is modified, very flexibly, remaining PET probe can also be synthesized with said apparatus certainly, only needs
Synthesis flow and corresponding pipeline connected mode are designed according to synthesis mode.
More than be exemplified as specific embodiment of the invention, it is clear that the present invention is not limited to above example, this area it is general
Logical technical staff directly derives from present disclosure or the deformation associated all should belong to protection scope of the present invention.
Claims (3)
1. a kind of Novel PET probe synthesis system, it is characterised in that including some PET probes synthetic towers, half prepare HPLC,
Rotary Evaporators；
Every PET probes synthetic tower includes synthetic tower main body and controller, and described synthetic tower main body includes going up from top to bottom
Lower movable upper tray, the fixed plate for fixing reaction bulb and lower tray moving up and down, in synthetic tower master
Some three-way magnetic valves are additionally provided with body, controller is used to control upper tray, the motion of lower tray and three-way magnetic valve
Break-make；
Described half preparation HPLC includes a radioactivity seeker, is installed in half preparation HPLC after UV detectors；
The synthesis system also includes wash-out magnetic valve and some solid-phase extraction columns, and isotopic ion is attracted to through eluting magnetic valve
On solid-phase extraction column, then the ion on solid-phase extraction column, solid-phase extraction column are eluted with corresponding isotopic ion eluent
Outlet is connected with a three-way magnetic valve on synthetic tower, and the product synthesized in PET probe synthetic towers is tentatively pure through solid-phase extraction column
Enter half preparation HPLC after change to be further purified, Rotary Evaporators evaporation solution concentration is entered afterwards and obtains PET probes.
2. Novel PET probe synthesis system as claimed in claim 1, it is characterised in that described synthetic tower main body middle and upper part
The up and down motion of column plate, move forward and backward and lower tray up and down motion by motor drive screw drive realize.
3. Novel PET probe synthesis system as claimed in claim 1, it is characterised in that described Rotary Evaporators include outer
Portion's control box, lifting and bath temperature for controlling direction of rotation and speed and water-bath.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201611088904.XA CN106749435A (en) | 2016-12-01 | 2016-12-01 | A kind of Novel PET probe synthesis system |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201611088904.XA CN106749435A (en) | 2016-12-01 | 2016-12-01 | A kind of Novel PET probe synthesis system |
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| CN106749435A true CN106749435A (en) | 2017-05-31 |
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| CN201611088904.XA Pending CN106749435A (en) | 2016-12-01 | 2016-12-01 | A kind of Novel PET probe synthesis system |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109806822A (en) * | 2019-01-30 | 2019-05-28 | 杭州吉蕊科技有限公司 | A kind of modularization, multi-functional PET probe Fully automated synthesis system |
Citations (5)
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|---|---|---|---|---|
| CN2468490Y (en) * | 2000-09-25 | 2002-01-02 | 杜宜奎 | Installation for prodn. of fluorine-18 making drug |
| CN101104627A (en) * | 2007-07-20 | 2008-01-16 | 张锦明 | 18F-FDG automatization synthetic method and device |
| CN202346771U (en) * | 2011-11-02 | 2012-07-25 | 张锦明 | Fluorine-18 and carbon-11 multifunctional synthesis module integrated device |
| CN102867559A (en) * | 2011-07-08 | 2013-01-09 | 复旦大学附属肿瘤医院 | Automated synthesizer of <18>F-marked PET (positron emission tomograph)/CT (computerized tomograph) molecular image probe |
| CN105031675A (en) * | 2015-07-22 | 2015-11-11 | 周彤 | Process and module capable of continuously synthesizing fluorine-18 radiopharmaceuticals at two times |
-
2016
- 2016-12-01 CN CN201611088904.XA patent/CN106749435A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN2468490Y (en) * | 2000-09-25 | 2002-01-02 | 杜宜奎 | Installation for prodn. of fluorine-18 making drug |
| CN101104627A (en) * | 2007-07-20 | 2008-01-16 | 张锦明 | 18F-FDG automatization synthetic method and device |
| CN102867559A (en) * | 2011-07-08 | 2013-01-09 | 复旦大学附属肿瘤医院 | Automated synthesizer of <18>F-marked PET (positron emission tomograph)/CT (computerized tomograph) molecular image probe |
| CN202346771U (en) * | 2011-11-02 | 2012-07-25 | 张锦明 | Fluorine-18 and carbon-11 multifunctional synthesis module integrated device |
| CN105031675A (en) * | 2015-07-22 | 2015-11-11 | 周彤 | Process and module capable of continuously synthesizing fluorine-18 radiopharmaceuticals at two times |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109806822A (en) * | 2019-01-30 | 2019-05-28 | 杭州吉蕊科技有限公司 | A kind of modularization, multi-functional PET probe Fully automated synthesis system |
| CN109806822B (en) * | 2019-01-30 | 2021-07-30 | 杭州吉蕊科技有限公司 | Modularized and multifunctional PET probe automatic synthesis system |
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