CN104262073A - Small modular multifunctional automatic 18F labelling PET (positron emission tomography) drug synthesizer - Google Patents
Small modular multifunctional automatic 18F labelling PET (positron emission tomography) drug synthesizer Download PDFInfo
- Publication number
- CN104262073A CN104262073A CN201410521021.8A CN201410521021A CN104262073A CN 104262073 A CN104262073 A CN 104262073A CN 201410521021 A CN201410521021 A CN 201410521021A CN 104262073 A CN104262073 A CN 104262073A
- Authority
- CN
- China
- Prior art keywords
- module
- fdg
- valve
- synthesis
- pet
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Abstract
The invention provides a small modular multifunctional automatic 18F labelling PET (positron emission tomography) drug synthesizer and relates to an automatic PET drug synthesizer. The small modular multifunctional automatic 18F labelling PET drug synthesizer comprises a single FDG (fluorodeoxyglucose) synthesis module or two FDG synthesis modules which are connected in series, namely a module FDG1 and a module FDG2, a PET drug product separating system and a control system, wherein the single FDG synthesis module or the two FDG synthesis modules which are connected in series are used for independently completing FDG synthesis or continuously completing double-batch FDG synthesis in a combined manner; the PET drug product separating system is connected with the single FDG synthesis module or a second module, namely the module FDG2, in the two FDG synthesis modules which are connected in series; and the control system is used for connecting and controlling the FDG synthesis module and the PET drug product separating system. The small modular multifunctional automatic PET drug synthesizer has the characteristics of ingenious structure, small size, simple mounting, friendly interface, simple operation, safety, stability, reliability, convenience in maintenance, powerful function and flexibility, is simple to mount and operate, and convenient to maintain, and the production requirement of 18F labelling PET drugs for the current market and scientific research can be met.
Description
Technical field
The present invention relates to pharmaceutical preparation facilities, particularly relate to a kind of PET (positron emission fault) medicine Fully automated synthesis instrument.
Background technology
2-
18f-2-DDG (FDG) is the most frequently used positron emission fault (PET) radiopharmaceuticals (also known as developer), has been widely used in PET clinical diagnosis and the curative effect evaluation of tumour, cardiovascular disorder and neuropsychiatric disease.But FDG also there will be false positive and false negative result when clinical examination, thus need imitated or develop multiple PET medicine, to improve the sensitivity of PET diagnosis, accuracy and specificity.FDG produces with specificity Fully automated synthesis instrument usually, could meet clinical PET needs.But along with continuous introduction and the development of PET technology, need clinically to produce multiple PET medicine, specificity Fully automated synthesis instrument can not meet the needs of increasing clinical PET drug manufacture.Thus, research and development multifunction automatic synthesizer is needed, for the production of various PET medicine, such as
11the various PET medicines of C mark,
18the various PET medicines of F mark.
PET medicine Fully automated synthesis instrument is primarily of reacting by heating synthesis system and high performance liquid chromatography (HPLC) separation system composition.At present, commercial multi-functional PET medicine Fully automated synthesis instrument mainly relies on import, and domestic multifunction automatic synthesizer is succeeded in developing and is converted into clinical application in recent years.But the multifunction automatic synthesizer of these commercial domestic and importeds all has larger limitation.The Tracerlab FX FN that import multifunction automatic synthesizer has General Electric Apparatus Co.'s (medical system) (GE company) to research and develop
18the Synthera system of F-multifunction automatic synthesizer, the Syn Chrom R & D multifunction automatic synthesizer of German Raytest company research and development, the research and development of Belgian IBA company and the multifunction automatic synthesizer etc. of Japanese strain friend company research and development.Although these companies have have researched and developed and have possessed two-tube heated reaction system in recent years, but the multifunction automatic synthesizer of domestic introduction only has single tube reacting by heating synthesis system mostly, the need of production of some complicated PET medicine cannot be met, and prices are rather stiff, volume is also comparatively large, is not easy to keep in repair (as the multifunction automatic synthesizer that GE company, Raytest company and Zhu You company research and develop); Or level of automation is too high, uses and lack handiness, the needs (IBA company Synthera system) of some PET drug manufacture can not be met.The production domesticization that Beijing PET company produces
18f multifunction automatic synthesizer, has two-tube heated reaction system and relatively cheap advantage.But synthesizer volume is greatly numerous, maintenance is inconvenient; Use coupling cock, maintenance warranty charges is higher.In addition, production domesticization and import multifunction automatic synthesizer all do not have product HPLC separation and purification post-heating to desolventize system, are thus unsuitable for some PET drug manufacture, are unsuitable for yet
11c marks the production of PET medicine.
Summary of the invention
For the shortcoming of prior art, the object of this invention is to provide a kind of small modules formula multifunction automatic PET pharmaceutical synthesis instrument, there is delicate structure, volume miniaturization, simple and easy, friendly interface, simple to operate, safe, stable, reliable, easy to maintenance, powerful and flexible and changeable feature are installed, PET medicine main in the market can be met namely
18the production of F-PET medicine.
Small modules formula multifunction automatic PET pharmaceutical synthesis instrument of the present invention, comprise: single FDG synthesis module, or two FDG synthesis modules and FDG1 module and FDG2 module of connecting, for completing separately FDG synthesis or completing two batches of FDG synthesis in combination continuously; PET medicament production separation system, is connected with single FDG synthesis module, or second module in the FDG synthesis module of connecting with two and FDG2 model calling; And Controlling System, for connecting and controlling described FDG synthesis module, described PET medicament production separation system.
According to the further feature of small modules formula multifunction automatic PET pharmaceutical synthesis instrument of the present invention, described single FDG synthesis module comprises: heated reaction system, comprising: round bottom reaction tubes, and the mouth of pipe is equipped with the sealing cover of band octal, and the first to the 6th hole is N
2sample under carrier band adds hand-hole, and seven apertures in the human head is FDG output of products hole, and octal is vacuum pump safety flack access aperture; Aluminium sheet well heater, is placed in the bottom of described round bottom reaction tubes, for heating the bottom conversion zone of described round bottom reaction tubes; N is provided with near conversion zone
2refrigerating unit; Sample adding system, comprising: the first to the 6th application of sample bottle 1-6, connects respectively and is used for input by N
2first group of 6 one-way valve V1 '-V6 ' of the sample of carrier band, and connect second group of 6 the one-way valve V1-V6 being used for sample being outputted to described sealed reaction tube respectively; Wherein, the sample of the first application of sample bottle 1 is at N
2the 12 T-valve (V12) is entered via the first one-way valve V1 of second group, with trapping by accelerator-produced under carrier band
18f
-sep-Pak QMA pillar, then import described round bottom reaction tubes by the 13 T-valve V13, another outlet of the 13 T-valve V13 connects
18o
-useless target Water Sproading bottle; Wherein, the sample of the 6th application of sample bottle 6 is at N
2the tenth T-valve V10 is output under carrier band; N
2or He gas transmission system, comprise the N connected successively
2or He source of the gas, total air valve, reducing valve, gas meter and related valve, N
2or He gas flows through first group of 6 one-way valve V1 '-V6 ' and inputs to the described first to the 6th application of sample bottle 1-6, part N after decompression
2also flow into the 7th T-valve V7 through anemometer and check valve, and enter reaction tubes further by the 8th one-way valve V8, for mixed reaction solution, then export through the 9th one-way valve V9; FDG output of products system, comprises the seven apertures in the human head output tube and the related valve that insert also through sealing cover bottom described round bottom reaction tubes, reacts the FDG product of generation at N in described round bottom reaction tubes
2under carrier band, the 7th T-valve V7 is outputted to through the 8th one-way valve V8, again through the tenth T-valve V10, by two Sep-Pak C-18 pillar guiding the 11 T-valve V11, an outlet of T-valve V11 is connected with waste liquid bottle, another outlet is connected with product-collecting bottle, between T-valve V11 and product-collecting bottle, arrange aseptic filter membrane; Vacuum pump system, comprises the 9th one-way valve V9, safety flack and vacuum pump, is inserted the octal of the sealing cover of described round bottom reaction tubes through the pipeline of safety flack by the 9th one-way valve V9.
According to the further feature of small modules formula multifunction automatic PET pharmaceutical synthesis instrument of the present invention, in the FDG synthesis module of described two series connection, the 11 T-valve V11 be directly connected with product-collecting bottle in first FDG synthesis module (i.e. FDG1 module), connects with the tenth T-valve V10 be connected with two Sep-Pak C18 pillar inlet pipes in second FDG synthesis module and FDG2 module.
According to the further feature of small modules formula multifunction automatic PET pharmaceutical synthesis instrument of the present invention, when described HPLC separation module is connected with FDG synthesis module, the outlet pipe of the 11 T-valve V11 be directly connected with product-collecting bottle of described FDG synthesis module is connected to described PET medicament production separation module.
According to the further feature of small modules formula multifunction automatic PET pharmaceutical synthesis instrument of the present invention, described PET medicament production separation system is HPLC separation system or pillar separation system, wherein, HPLC separation system comprises product HPLC separation and purification post-heating and desolventizes system, can be used for the separation and purification of all PET medicines.
According to the further feature of small modules formula multifunction automatic PET pharmaceutical synthesis instrument of the present invention, change described each FDG synthesis module, HPLC separation system and pipeline connecting mode, automatic production can comprise all of FDG
18f marks PET medicine.
According to the further feature of small modules formula multifunction automatic PET pharmaceutical synthesis instrument of the present invention, change control program, increase and decrease application of sample bottle number and change pipeline connecting mode and radioactive source condition under, described FDG1 module and FDG2 module can upgrade to respectively
11cH
3br synthesis module and
11c-methylates synthesis module, for
11cH
3i or
11cH
3br or
11cH
3-Triflate, conventional
11c-methylate medicine and
11the production of C-acetate.
Compared with prior art, small modules formula multifunction automatic PET pharmaceutical synthesis instrument of the present invention has following characteristics and advantage:
(1) PET pharmaceutical synthesis instrument of the present invention designs based on Good Manufacturing Practice and Quality Control of Drug (GMP) theory, therefore possesses miniaturization, modularization, multi-functional advantage.This PET pharmaceutical synthesis instrument is not only focused on and ensures instrument security, stability, reliability, servicing ease and quality product, and carries out complete monitoring and recording parameters to whole production process, embodies the overall development direction of novel automatic synthesizer.
(2) PET pharmaceutical synthesis instrument of the present invention has delicate structure, volume miniaturization, installs simple and easy, simple to operate, easy to maintenance, powerful and flexible and changeable feature, can be used for the various PET medicine of full-automatic production and microsynthesis.
(3) the optional fully automated of PET drug manufacture whole process controls, and manual mode also can be selected to complete.Simplified cleaning test kit is installed, selects self-check program, after completing automatization self-inspection and cleaning, next step PET medicine automatic production can be carried out.Simple and easy production test kit is installed, selects fully automated sequence of control, the automatic production of PET medicine can be carried out.
(4) single small-sized FDG synthesis module is the elementary cell forming Fully automated synthesis instrument, user can select to install single specificity FDG synthesis module (single module formula FDG Fully automated synthesis instrument) or multiple specificity FDG synthesis module (multi-module type FDG Fully automated synthesis instrument) as required, and single FDG synthesis module is easy to upgrade to multiple FDG synthesis module.
(5) single module formula FDG Fully automated synthesis instrument can realize single batch of FDG production.The upgrading of single module formula FDG Fully automated synthesis instrument is simple, and two single module formula FDG Fully automated synthesis instrument can realize two batches of 18F-FDG automatic productions, also can realize other PET medicine (as
18f-FMISO,
18f-FLT and
18f-FPA etc.) automatic production.
(6) two FDG synthesis module+HPLC separation modules, can upgrade to small modules formula multi-functional PET medicine Fully automated synthesis instrument, can meet the production of all PET medicines in the market and the synthesis of Novel PET medicine.
(7) two single module formula FDG Fully automated synthesis instrument, change control program, increase and decrease application of sample bottle number and change pipeline connecting mode and radioactive source condition under, also can upgrade to respectively
11cH
3br synthesis module and
11c-methylates synthesis module, for
11cH
3i (or
11cH
3br) or
11cH
3-Triflate, conventional
11c-methylate medicine and
11the production of C-acetate.Upgrade to further
11the multi-functional synthesizer of C small modules formula:
11cH
3br synthesis module+
11c-methylates synthesis module+HPLC separation module, can produce all
11c PET medicine.
Accompanying drawing explanation
Below in conjunction with accompanying drawing, the present invention is described in further detail.
Fig. 1 is composition structural representation of the present invention.
Fig. 2 is the composition schematic diagram of FDG1 module.
Fig. 3 is the composition schematic diagram of FDG2 module.
Fig. 4 is the reactor heating system schematic of FDG1 module.
Embodiment
Refer to Fig. 1, PET medicine Fully automated synthesis instrument of the present invention comprises: single FDG synthesis module, or two FDG synthesis modules and FDG1 module and FDG2 module of connecting, for completing separately FDG synthesis or completing two batches of FDG synthesis in combination continuously; PET medicament production separation system, is connected with single FDG synthesis module, or second module in the FDG synthesis module of connecting with two and FDG2 model calling; And Controlling System, for connecting and controlling described FDG synthesis module, described PET medicament production separation system.
Below each integral part is elaborated one by one:
(1) FDG synthesis module
1, heated reaction system, comprising: round bottom reaction tubes, and the mouth of pipe is equipped with the sealing cover of band octal, and the first to the 6th hole is N
2sample under carrier band adds hand-hole, and seven apertures in the human head is FDG output of products hole, and octal is vacuum pump safety flack access aperture; Aluminium sheet well heater, is placed in the bottom of described round bottom reaction tubes, for heating the bottom conversion zone of described round bottom reaction tubes; N is provided with near conversion zone
2refrigerating unit.
2, sample adding system, comprising: the first to the 6th application of sample bottle 1-6, connects respectively and is used for input by N
2first group of 6 one-way valve V1 '-V6 ' of the sample of carrier band, and connect second group of 6 the one-way valve V1-V6 being used for sample being outputted to described sealed reaction tube respectively.
The sample of the first application of sample bottle 1 is at N
2the 12 T-valve (V12) is entered via the first one-way valve V1 of second group, with trapping by accelerator-produced under carrier band
18f
-sep-Pak QMA pillar, then import described round bottom reaction tubes by the 13 T-valve V13, another outlet of the 13 T-valve V13 connects
18o
-useless target Water Sproading bottle.
The sample of the 6th application of sample bottle 6 is at N
2the tenth T-valve V10 is output under carrier band.
3, N
2or He gas transmission system, comprise the N connected successively
2or He source of the gas, total air valve, reducing valve, gas meter and related valve, N
2or He gas flows through first group of 6 one-way valve V1 '-V6 ' and inputs to the described first to the 6th application of sample bottle 1-6, part N after decompression
2also flow into the 7th T-valve V7 through anemometer and check valve, and enter reaction tubes further by the 8th one-way valve V8, for mixed reaction solution, then export through the 9th one-way valve V9.
4, FDG output of products system, comprises the seven apertures in the human head output tube and the related valve that insert also through sealing cover bottom described round bottom reaction tubes, reacts the FDG product of generation at N in described round bottom reaction tubes
2under carrier band, the 7th T-valve V7 is outputted to through the 8th one-way valve V8, again through the tenth T-valve V10, by two Sep-Pak C-18 pillar guiding the 11 T-valve V11, an outlet of T-valve V11 is connected with waste liquid bottle, another outlet is connected with product-collecting bottle, between T-valve V11 and product-collecting bottle, arrange aseptic filter membrane; Vacuum pump system, comprises the 9th one-way valve V9, safety flack and vacuum pump, is inserted the octal of the sealing cover of described round bottom reaction tubes through the pipeline of safety flack by the 9th one-way valve V9.
According to the further feature of small modules formula multifunction automatic PET pharmaceutical synthesis instrument of the present invention, in the FDG synthesis module of described two series connection, the 11 T-valve V11 be directly connected with product-collecting bottle in first FDG synthesis module (i.e. FDG1 module), connects with the tenth T-valve V10 be connected with two Sep-Pak C18 pillar inlet pipes in second FDG synthesis module and FDG2 module.
According to the further feature of small modules formula multifunction automatic PET pharmaceutical synthesis instrument of the present invention, when described HPLC separation module is connected with FDG synthesis module, the outlet pipe of the 11 T-valve V11 be directly connected with product-collecting bottle of described FDG synthesis module is connected to described PET medicament production separation module.
(2) PET medicament production separation module
The PET medicament production separation system that the present invention adopts can be HPLC separation system, or pillar separation system all can adopt existing business-like separation system, or according to the substitute products of identical principle design.
Such as, the HPLC separation system of GE TRACERLab FX FN Fully automated synthesis instrument can be adopted, and the HPLC separation system of SUMITOMO CHEMICAL fluorine-18 multifunctional synthesizer.
1 FDG synthesis module adds 1 HPLC separation module, can be used for one kettle way and completes great majority
18f marks the automatic production of PET medicine.Two FDG synthesis modules add 1 HPLC separation module, can be used for comprising
18f-fluoro DOPA (FDOPA) is interior all
18f marks the automatic production of PET medicine.
For many conventional PET medicines, pillar separation system also can be adopted to replace HPLC separation system to carry out separation and purification.
(3) Controlling System
Controlling System can be joined with existing electronic control unit and computer, electronic control unit is for realizing the control of main frame to Fully automated synthesis system, numerary signal and electrical signal are changed mutually, computer is synthesized by the full-automation of software one-key operation PET medicine, and can show the state of each parts of synthesizer in real time.
Computerized control system comprises electronic control unit and computer.Numerary signal and electrical signal, for realizing the control of main frame to Fully automated synthesis system, are changed mutually by electronic control unit.The electronic control unit be equipped with can not only realize the conversion of signal, and can be shown the working order of synthesizer all parts in real time by hyperchannel.Can be equipped with high-end notebook PC as main control system, operation interface is windows system, has very high compatibility, is convenient to user operation.
Intelligent Control Software is the core technology realizing the automatic production of multiple PET medicine.The design requirements of software is the full-automation synthesis of energy one-key operation PET medicine, and the state of each parts of synthesizer can be shown in real time, as temperature, radioactive counts, ultraviolet absorption peak etc., and parametric line can be generated in real time, as the foundation of production process validity, this is also an important idea of GMP.Not modifiable production report can be generated after production terminates immediately, ensure the true record having production result.The whole process of PET pharmaceutical synthesis is that fully automated controls, and manual mode also can be selected to complete.Control software design comprises the composite software of various PET medicine, is convenient to different user choice for use according to the actual requirements, also can edit different simple sequence of control and carry out new drug synthesis.Synthesis sequence of control comprises: FDG synthesis program, 18F-FMISO synthesis program, 18F-FLT synthesis program, 18F-FCH synthesis program, 18F-FECH synthesis program, 18F-FPA synthesis program, 18F-FAC synthesis program, 18F-FHBG synthesis program, 18F-NFP synthesis program, 18F-SFB synthesis program, 18F-FDOPA synthesis program.
Embodiment 1 FDG Fully automated synthesis
Self-inspection.Steel cylinder pressure valve pressure is regulated to be greater than 0.5MPa, application of sample N
2pressure is 0.2MPa, and blow evaporation N
2flow is 80-100ml/min; Respectively in No. 1, No. 2, No. 3 and kingpin, add water, acetonitrile, acetonitrile and water 2-3ml successively.Connect each pipeline, after refuse bottle and receiving flask are installed, start self-check program.Check heating unit and charge delivery mechanism whether normal.
Prepare before producing.
1. prepare QMA pillar.Get 0.3M NaHCO
3(or Na
2cO
3) 10ml, cross Sep Pak light QMA pillar, get rid of surplus liquid.Get 10ml injection water, cross QMA post, get rid of surplus liquid.Or get 10ml trifluoroacetic acid aqueous solution again, cross QMA post, get rid of surplus liquid.
The process of 2.C-18 pillar.Get 10ml dehydrated alcohol, respectively by two Sep Pak plus C-18 pillars, removing surplus liquid; Use the process of 10ml injection water again, with empty syringe removing surplus liquid.
3.Aluminum-N pillar and the process of SCX pillar.Get 10ml injection water, after Sep Pak plus Aluminum-N pillar and SCX pillar, use the process of 10ml injection water respectively, with empty syringe removing surplus liquid.
4. connect pillar and filter membrane.Sep Pak light QMA pillar is arranged on corresponding position in synthesizer; Two Sep Pak plus C-18 pillars are linked together, is arranged on corresponding position in synthesizer; Together with being linked in sequence with Sep Pak plus Aluminum-N pillar by SCX pillar, be arranged on corresponding position in synthesizer; Whole radiosynthesis system by being correctly sequentially connected on Fully automated synthesis instrument, and is placed in synthesis hot cell by pillar and pipeline.
5. product-collecting bottle is installed.Product-collecting bottle is loaded onto 0.22 μm × 25mm sample introduction sterilised membrane filter and aseptic exhaust filter membrane, be connected in synthesizer on request, and be placed in packing hot cell.
6. application of sample.Following reagent is added on request in each bottle of Fully automated synthesis instrument.
Automatic production.Player's dynamic circuit connector becomes the mode, and after waiting accelerator-produced radionuclides to be all transferred to QMA post, start-up simulation machine synthesizes sequence of control automatically, and whole process about 26 minutes, carries out quality test after synthesis, prints and produces report.
From the menu of software, select FDG Fully automated synthesis program, press " bringing into operation " button, complete FDG Fully automated synthesis under the control of the computer.
(1)
18f-F-traps.Passed through by magnetic resonance acceleator
18o (p, n)
18the 18F-F-that F nuclear reaction is produced, at He or N
2under gas transmission, through being placed in the SEP-PAK QMA pillar of radioactive activity measuring meter,
18f-F-is trapped on post,
18o-water is collected in O-18 Water Sproading bottle 7.
(2) acetonitrile water evaporation.Open valve order: V9 → V13 → V12 → V1 → V1 ', under N2 effect, will containing the acetonitrile solution of K222 in headpin
18f-F-wash-out enters in sealed reaction bottle 10.Start vacuum pump, heating mixing solutions to 60 ~ 95 DEG C, evaporated under reduced pressure, obtain dry [K/K222]+
18f-mixture, waste liquid is absorbed by safety flack cold-trap 8.
(3) fluoridation.At N
2under effect, the precursor mannose triflate acetonitrile solution in No. 3 bottles is pressed in reaction flask 10,85 DEG C of reacting by heating 5min.After fluoridation completes, concentrating under reduced pressure, cooling.
(4) fluorinated intermediates is caught at post.Under N2 airflow function, H in fluorinated intermediates and No. 4 and No. 2 bottles
2o mixture is transmitted through 2 SEP-PAK plus C18 pillars, containing acetonitrile waste collection in refuse bottle 11, and two pillar N
2dry up.
(5) in post basic hydrolysis.At N
2under airflow function, in kingpin, NaOH solution is pressed in reaction flask 10, and is loaded in SEP-PAK C18 pillar, and hydrolysis time is about 2min.
(6) neutralization and separation and purification.Under N2 airflow function, the water in No. 6 bottles is successively by 2 SEP-PAK plus C18 pillars, SEP-PAK Al
2o
3neutral pillar, SCX pillar and sterilised membrane filter, the FDG aqueous solution is collected in sterile product bottle 9, finally,
18f-FDG injection liquid.FDG does not correct putting productive rate >=50%, generated time≤25min, radiochemicsl purity >99%.
2-
18f-fluoropropionic acid salt (18F-FPA) synthesis program and
18f-fluoroacetate (
18f-FAC) synthesis program and FDG Fully automated synthesis program similar, change corresponding reagent, get final product automatic production
18f-FPA and
18f-FAC injection liquid.
18the total generated time of F-FAC is less than 20min, and do not correct putting productive rate and reach 60%, radiochemicsl purity is greater than 95%.
18the total generated time of F-FPA is less than 30min, and not correcting putting productive rate is 46%, and radiochemicsl purity is greater than 95%.
Embodiment 2 18F-FLT Fully automated synthesis
Prepare before producing.In software package inediting 3 '-deoxidation-3 '-
18f-fluoro thymidine (18F-FLT) Fully automated synthesis program (in Fig. 2 FDG1-fluorochemical portion and HPLC part).In appropriate place, Sep Pak Light QMA pillar and Sep Pak Al are installed
2o
3neutral separation pillar.K222 solution is added in headpin, namely add 1.5ml acetonitrile water (volume ratio 10/1) solution, include 15mg phase-transfer catalyst amino-polyether 4,7,13,16,21,24-six oxa--1,10-diazabicyclo [8,8,8] 26 carbon alkane (Kryptofix2.2.2, K222) and 3mg K
2cO
3; The acetonitrile solution (1mL) including 15mg precursor 3-N-t-tertbutyloxycarbonyl-1-[5 '-O-(4,4 '-dimethoxytrityl)-2 '-deoxidation-3 '-O-(4-nitrobenzenesulfonyl)-β-D-threo form Ah furyl glycosyl] thymus pyrimidine is added in No. 3 bottles; No. 4 bottles add 1mol/L hydrochloric acid (1mL); Kingpin adds 1mol/L sodium hydroxide solution (1mL); No. 6 bottles add the alcohol-water leacheate (1mL) that volume ratio is less than 10:90.Close hot cell protective door.
Automatic production.Select in the menu of software
18f-FLT synthesis program, presses " bringing into operation " button, completes 18F-FLT Fully automated synthesis under the control of the computer.
(1) [K/K222]+
18the preparation of F-mixture.Passed through by magnetic resonance acceleator
18o (p, n)
18f nuclear reaction is produced
18f-F-, at N
2by Sep-Pak Light QMA negatively charged ion pillar under gas transmission,
18f-F-is trapped in pillar, H
2 18o is collected in O-
18in Water Sproading bottle.At N
2under effect, containing K in headpin
2cO
3will with the acetonitrile solution of Kryptofix 2.2.2.
18f-F-wash-out enters in sealed reaction bottle, starts vacuum pump, heating mixing solutions to 60 ~ 95 DEG C, and evaporated under reduced pressure, obtain dry [K/K222]+18F-mixture, waste liquid is absorbed by safety flack cold-trap.
(2) fluoridation.At N
2under effect, the precursor solution in No. 3 bottles is pressed in reaction flask, 110 DEG C of heated sealed reaction 5min.
(3) hydrolysis reaction.After fluoridation completes, cooling, in No. 4 bottles, HCl solution is pressed in reaction flask, 105 DEG C of reacting by heating 5min, cooling.
(4) neutralization and separation and purification.After hydrolysis, reaction flask is cooled to 50 DEG C, and in kingpin, sodium hydroxide solution is pressed in reaction flask, neutralizing acid solution.Thick product is by Sep-Pak Al
2o
3pillar, unreacted
18f-F-is adsorbed.In No. 6 bottles, HPLC leacheate is at N
2by Sep-Pak Al under pressure effect
2o
3pillar, is collected in the transfer bottle of HPLC part.Transfer bottle in thick product through the further separation and purification of HPLC C18 post,
18f-FLT is collected in intermediate collection bottle.Finally by N
2effect,
18f-FLT solution is transferred in heated sealed bottle, through heating under reduced pressure is concentrated remove ethanol after, use normal saline dilution.
18after F-FLT diluent crosses sterilised membrane filter, be collected in sterile product bottle,
18f-FLT injection liquid.HPLC separation condition: moving phase is water-ethanol solution (volume ratio 90:10), flow velocity 8mL/min, and ultraviolet (UV) determined wavelength is 254nm.
18the total generated time of F-FLT is about 60min, and uncorrected putting productive rate is greater than 20%, and radiochemicsl purity is greater than 95%.
1-H-1-(3-
18f-2-hydroxypropyl)-2-nitroimidazole (
18f-FMISO), O-(2-
18f-fluoroethyl groups)-TYR (
18and 9-(4-F-FET)
18f-3-methylol-butyl) guanine (
18f-FHBG) synthesis program and 18F-FLT Fully automated synthesis program similar, change corresponding reagent, get final product automatic production
18f-FMISO,
18f-FET and
18f-FHBG injection liquid.
18the total generated time of F-FMISO is about 60min, and putting productive rate is greater than 60%, radiochemicsl purity difference 99%.
18the total generated time of F-FET is about 50min respectively, and uncorrected putting productive rate is all greater than 20%, and radiochemicsl purity is all greater than 95%.
18the total generated time of F-FHBG is about 60min respectively, and uncorrected putting productive rate is all greater than 10%, and radiochemicsl purity is all greater than 95%.
Embodiment 3
18f-FCH Fully automated synthesis
Prepare before producing.Software package inediting (N-18F-fluoromethyl) choline (
18f-FCH) Fully automated synthesis program (in Fig. 2 FDG1-fluorochemical portion and FDG2-transform portion).At correct position, 1 Sep Pak Light QMA pillar, 3 Sep Pak plus SiO2 pillars, 1 Sep Pak plus tC18 pillar and Sep Pak CM pillars are installed.FDG1-fluorochemical portion: add 1.5mL K222 solution in headpin; Acetonitrile (2mL) solution containing methylene bromide (300 μ L) is added in No. 3 bottles.FDG2-transform portion: load N, N-dimethylethanolamine 0.4mL in Sep Pak plus tC18 pillar; Headpin adds 10mL ethanol; No. 2 bottles add 10mL water; No. 3 bottles add 3mL physiological saline.Close hot cell protective door.
Automatic production.In the menu of software, select 18F-FCH synthesis program, press " bringing into operation " button, complete under the control of the computer
18f-FCH Fully automated synthesis.
(1) [K/K222]+
18the preparation of F-mixture.Passed through by magnetic resonance acceleator
18o (p, n)
18f nuclear reaction is produced
18f-F-, at N
2by Sep-Pak Light QMA negatively charged ion pillar under gas transmission, 18F-F-is trapped in pillar, H
2 18o is collected in O-18 Water Sproading bottle.At N
2under effect, in headpin, K222 acetonitrile solution will
18f-F-wash-out enters in sealed reaction bottle, starts vacuum pump, heating mixing solutions to 60 ~ 95 DEG C, evaporated under reduced pressure, obtain dry [K/K222]+
18f-mixture, waste liquid is absorbed by safety flack cold-trap.
(2) fluoridation.At N
2under effect, the precursor methylene bromide solution in No. 3 bottles is pressed in reaction flask, 80 DEG C of heated sealed reaction 1min.
(3) alkylated reaction.After fluoridation completes, at N
2under effect, heating evaporation
18fCH2Br is about 10min.Produce
18three the Sep Pak plus SiOs of FCH2Br by being connected successively
2after pillar, react with precursor N, N-dimethylethanolamine in Sep Pak plus tC18 pillar.
18fCH2Br is captured in Sep Pak CM pillar, and after reaction, waste liquid enters into waste liquid bottle.
(4) separation and purification.With ethanol and water drip washing Sep Pak plus tC18 pillar and Sep Pak CM pillar respectively, leacheate enters into waste liquid bottle.With physiological saline wash-out 18F-FCH from Sep Pak plus tC18 pillar and Sep Pak CM pillar, be collected in sterile product bottle,
18f-FCH injection liquid.
18the total generated time of F-FCH is about 35min, and uncorrected putting productive rate is greater than 10%, and radiochemicsl purity is greater than 95%.
Embodiment 4
18f-FECH Fully automated synthesis
Prepare before producing.At software package inediting (N-
18f-fluoroethyl groups) choline (
18f-FECH) Fully automated synthesis program (in Fig. 2 FDG1-fluorochemical portion and FDG2-transform portion).At FDG1-fluorochemical portion correct position, 1 Sep Pak Light QMA pillar is installed, install 1 Sep Pak plus tC18 pillar, 1 Sep Pak CM pillar and 2 Sep Pak plus Silica pillars at FDG2-transform portion correct position, rear both use water 10mL process respectively.FDG1-fluorochemical portion: add 1.5mL K222 solution in headpin; 96% ethanol 4mL in No. 2 bottles; Add in No. 3 bottles acetonitrile (1mL) solution added containing precursor 1，2-ethandiol two p-toluenesulfonic esters (15mg); N is added, N-dimethylethanolamine 0.4mL in No. 4 bottles.FDG2-transform portion: headpin adds 10mL ethanol; No. 2 bottles add 10mL water; No. 3 bottles add 10mL physiological saline.Close hot cell protective door.
Automatic production.Select in the menu of software
18f-FECH synthesis program, presses " bringing into operation " button, completes 18F-FECH Fully automated synthesis under the control of the computer.
(1) [K/K222]+
18the preparation of F-mixture.Passed through by magnetic resonance acceleator
18o (p, n) 18F nuclear reaction is produced
18f-F-, at N
2by Sep-Pak Light QMA negatively charged ion pillar under gas transmission,
18f-F-is trapped in pillar, H
2 18o is collected in O-18 Water Sproading bottle.At N
2under effect, in headpin, K222 acetonitrile solution will
18f-F-wash-out enters in sealed reaction bottle, starts vacuum pump, heating mixing solutions to 60 ~ 95 DEG C, and evaporated under reduced pressure, obtain dry [K/K222]+18F-mixture, waste liquid is absorbed by safety flack cold-trap.
(2) fluoridation.At N
2under effect, the precursor solution in No. 3 bottles is pressed in reaction flask, after 90 DEG C of heated sealed reaction 5min, and evaporated under reduced pressure acetonitrile.
(3) alkylated reaction.After fluoridation completes, at N
2under effect, in No. 4 bottles, N, N-dimethylethanolamine is press-fit in reaction flask, 100 DEG C of heated sealed reaction 5min.Cooling, in No. 2 bottles, 96% ethanol is press-fit into dilute reaction solution in reaction flask, and by 1 Sep Pak plus tC18 pillar, 1 Sep Pak CM pillar and 2 Sep Pak plus Silica pillars, waste reaction solution enters into waste liquid bottle.
(4) separation and purification.With 10mL ethanol and 10mL water above-mentioned 4 pillars of drip washing respectively, leacheate enters into waste liquid bottle.With physiological saline wash-out from above-mentioned pillar
18f-FECH, is collected in sterile product bottle after crossing sterilised membrane filter,
18f-FECH injection liquid.
18the total generated time of F-FECH is about 35min, and uncorrected putting productive rate is greater than 35%, and radiochemicsl purity is greater than 95%.
Embodiment 5
18f-SFB Fully automated synthesis
Prepare before producing.At software package inediting N-succinimide-4-
18f-fluorobenzoate (
18f-SFB) Fully automated synthesis program (in Fig. 2 FDG1-fluorochemical portion and FDG2-transform portion).At FDG1-fluorochemical portion correct position, 1 Sep Pak Light QMA pillar is installed; At FDG2-transform portion correct position, 1 Sep Pak plus C18 pillar, a SCX pillar and a Sep Pak Al are installed
2o
3neutral pillar.FDG1-fluorochemical portion: in headpin, adds 1.5mL K222 acetonitrile solution; 1.0mol/L tetrapropylammonium hydroxide salt brine solution (20 μ L) and acetonitrile (1mL) is added in No. 2 bottles; The acetonitrile solution (1mL) containing precursor 4-(trifluoromethanesulfonic acid leptodactyline) ethyl benzoate 5mg is added in No. 3 bottles; 5% acetic acid 9mL is added in No. 4 bottles; N is added, N, N', N'-tetramethyl--O-N-succimide in kingpin) phosphofluoric acid urea salt (HSTU) (12mg) acetonitrile solution (1mL); 15mL water is added in No. 6 bottles.FDG2-transform portion: add 10% acetonitrile solution (15mL) in No. 2 bottles; Acetonitrile (2mL) is added in No. 3 bottles.
Automatic production.Select in the menu of software
18f-SFB synthesis program, presses " bringing into operation " button, completes 18F-SFB Fully automated synthesis under the control of the computer.
(1) preparation of [K/K222]+18F-mixture.Passed through by magnetic resonance acceleator
18o (p, n) 18F nuclear reaction is produced
18f-F-, at N
2by Sep-Pak Light QMA negatively charged ion pillar under gas transmission, 18F-F-is trapped in pillar, H
2 18o is collected in O-18 Water Sproading bottle.At N
2under effect, in headpin, K222 acetonitrile solution will
18f-F-wash-out enters in sealed reaction bottle, starts vacuum pump, heating mixing solutions to 60 ~ 95 DEG C, evaporated under reduced pressure, obtain dry [K/K222]+
18f-mixture, waste liquid is absorbed by safety flack cold-trap.
(2) fluoridation.At N
2under effect, precursor 4-(trifluoromethanesulfonic acid leptodactyline) the ethyl benzoate acetonitrile solution in No. 3 bottles is pressed in reaction flask, 90 DEG C of heated sealed reaction 5min.After fluoridation completes, cooling.
(3) hydrolysis reaction.In No. 2 bottles, the acetonitrile solution of tetrapropylammonium hydroxide salt is added in reaction flask, 90 DEG C of hydrolysis 3min, azeotropic solvent evaporated.
(4) condensation reaction.N, N, N', N'-tetramethyl--O-N-succimide in kingpin) phosphofluoric acid urea salt acetonitrile solution is added in reaction flask, 90 DEG C of reacting by heating 5min.
(5) little column separating purification.Cooling reaction flask, to add in No. 4 bottles water in 5% acetic acid and No. 6 bottles successively, mixture is successively by SEP-PAK plus C18 pillar, SEP-PAK Al
2o
3pillar and SCX pillar.With the above-mentioned pillar of 10% acetonitrile solution drip washing in FDG2-transform portion No. 2 bottles, and use N
2dry up pillar.Finally, with acetonitrile product in No. 3 bottles, be collected in the dry reaction bottle of FDG2-transform portion, at N
2act on lower 60 DEG C of heating evaporated under reduced pressure solvents, obtain dry product
18f-SFB.
18the total generated time of F-SFB is less than 50min, and uncorrected putting productive rate is greater than 25%, and radiochemicsl purity is greater than 95%.
Embodiment 6
18f-NFP Fully automated synthesis
Prepare before producing.At software package inediting 2-
18f-fluoropropionic acid-4-nitro phenyl ester (
18f-NFP) Fully automated synthesis program (Fig. 2).At FDG1-fluorochemical portion correct position, 1 Sep Pak Light QMA pillar, Oasis HLB pillar and anhydrous Na are installed
2sO
4dry pillar; FDG1-fluorochemical portion pipeline is connected slight change with FDG2-transform portion pipeline and HPLC part pipeline.FDG1-fluorochemical portion: in headpin, adds 1.5mLK222 acetonitrile solution; Add water in No. 2 bottles 1mL; The acetonitrile solution (1mL) containing precursor 2-ethyl bromide 65mg is added in No. 3 bottles; Acetonitrile (1mL) solution containing 0.2M KOH (0.15mL) is added in No. 4 bottles; Two (p-nitrophenyl) carbonic ether (NPC, 30mg) acetonitrile (1mL) solution is added in kingpin; The acetic acid solution 1mL of 5% is added in No. 6 bottles.FDG2-transform portion: add ether (8mL) in headpin.HPLC part: add 0.1% trifluoroacetic acid (TFA) aqueous solution (40mL) in No. 16 bottles.
Automatic production.In the menu of software, select 18F-NFP synthesis program, press " bringing into operation " button, complete 18F-NFP Fully automated synthesis under the control of the computer.
(1) preparation of [K/K222]+18F-mixture.Passed through by magnetic resonance acceleator
18o (p, n)
18f nuclear reaction is produced
18f-F-, at N
2by Sep-Pak Light QMA negatively charged ion pillar under gas transmission,
18f-F-is trapped in pillar, H
2 18o is collected in O-18 Water Sproading bottle.At N
2under effect, in headpin, K222 acetonitrile solution will
18f-F-wash-out enters in sealed reaction bottle, starts vacuum pump, heating mixing solutions to 60 ~ 95 DEG C, evaporated under reduced pressure, obtain dry [K/K222]+
18f-mixture, waste liquid is absorbed by safety flack cold-trap.
(2) fluoridation.At N
2under effect, the precursor 2-ethyl bromide acetonitrile solution in No. 3 bottles is pressed in reaction flask, 100 DEG C of heated sealed reaction 8min.After fluoridation completes, cooling.
(3) hydrolysis reaction.In No. 4 bottles, KOH solution is added in reaction flask, 100 DEG C of hydrolysis 10min, azeotropic solvent evaporated.
(4) condensation reaction.In kingpin, NPC acetonitrile solution is added in reaction flask, 100 DEG C of reacting by heating 10min.
(5) HPLC separation and purification.Cooling reaction flask, add 5% acetic acid solution in No. 6 bottles, mixture is collected in No. 11 bottles through the V13 of FDG2-transform portion.Start HPLC system, in containing No. 16 bottles of 40mL 0.1%TFA, collect 18F-NFP component.
18f-NFP component passes through V10, Oasis HLB pillar of V13, FDG1-fluorochemical portion and the V11 of FDG1-fluorochemical portion of FDG2-transform portion,
18f-NFP is captured in Oasis HLB pillar.Water wash Oasis HLB pillar in No. 4 bottles of FDG1-fluorochemical portion, N
2, moisture in decompression pressure-vaccum dry pillar.In the headpin of FDG2-transform portion in ether wash-out Oasis HLB pillar
18f-NFP, enters in the reaction flask of FDG2-transform portion.At N
2act on lower 60 DEG C of heating evaporated under reduced pressure solvents, obtain dry product
18f-NFP.
18the total generated time of F-NFP is less than 60min, and uncorrected putting productive rate is greater than 25%, and radiochemicsl purity is greater than 95%.
Embodiment 7
18f-FDOPA Fully automated synthesis
Prepare before producing.At software package inediting 6-
18f-L-3,4-(fluoro dihydroxyphenylanaline) (
18f-FDOPA) Fully automated synthesis program (Fig. 2).At FDG1-fluorochemical portion correct position, 1 Sep Pak Light QMA pillar, Sep Pak Plus tC18 pillar and anhydrous K are installed
2cO
3dry pillar; FDG1-fluorochemical portion pipeline is connected slight change with FDG2-transform portion pipeline and HPLC part pipeline.FDG1-fluorochemical portion: in headpin, adds 1.5mL K222 acetonitrile solution; 0.8mL 57%HI is added in No. 2 bottles; Dimethyl sulfoxide (DMSO) (DMSO) solution (1mL) containing precursor 6-nitro piperonylaldehyde 12mg is added in No. 3 bottles; 20mL water is added in No. 4 bottles; 20mL water is added in kingpin; 6mg/mL NaBH is added in No. 6 bottles
4solution 3mL.FDG2-transform portion: add water (5mL) in headpin; Water (5mL) is added in No. 2 bottles; Toluene (3mL) is added in No. 3 bottles; 1.0mL 57%HI is added in No. 4 bottles; 50mM acetic acid (pH4) solution 2mL is added in kingpin; N-(phenylbenzene methene) tert-butyl glycinate (25mg), phase-transfer catalyst (2-3mg), CsOHH is added in reaction flask
2o (150mg) or 9M KOH 200 μ L.HPLC part: add 50mM acetic acid (pH4) solution 1mL in No. 11 bottles, include 0.57mM xitix and 1.00mM EDTA.
Automatic production.In the menu of software, select 18F-FDOPA synthesis program, press " bringing into operation " button, complete 18F-FDOPA Fully automated synthesis under the control of the computer.
(1) [K/K222]+
18the preparation of F-mixture.Passed through by magnetic resonance acceleator
18o (p, n) 18F nuclear reaction is produced
18f-F-, at N
2by Sep-Pak Light QMA negatively charged ion pillar under gas transmission,
18f-F-is trapped in pillar, H
2 18o is collected in O-18 Water Sproading bottle.At N
2under effect, in headpin, K222 acetonitrile solution will
18f-F-wash-out enters in sealed reaction bottle, starts vacuum pump, heating mixing solutions to 60 ~ 95 DEG C, evaporated under reduced pressure, obtain dry [K/K222]+
18f-mixture, waste liquid is absorbed by safety flack cold-trap.
(2) fluoridation.At N
2under effect, the precursor 6-nitro piperonylaldehyde DMSO solution in No. 3 bottles is pressed in reaction flask, 140 DEG C of heated sealed reaction 5min.After fluoridation completes, cooling.Add 20mL water dilute reaction solution in No. 4 bottles.By Sep Pak Plus tC18 pillar, with 20mL water washing in kingpin, N2 dries up.
(3) reduction iodination reaction.At N
2under effect, NaBH in No. 6 bottles
4solution passes through tC18 pillar, with water washing in the headpin in FDG2-transform portion, and N
2dry up.Add 57%HI in No. 2 bottles, in pillar, keep 2min, with water washing in No. 2 bottle of in FDG2-transform portion, N
2dry up pillar.With toluene wash pillar in No. 3 bottles, and pass through anhydrous K
2the dry pillar of CO3, enters in the reaction flask in FDG2-transform portion.
(4) alkylated reaction.The 2-generated
18n-(phenylbenzene methene) tert-butyl glycinate in F-4,5-fluoro methylene dioxy base benzyl iodide and FDG2-transform portion reaction flask, at stirring at room temperature reaction 5min, generates
18f-fluoro intermediate compound.
(5) hydrolysis reaction.Add the 57%HI in FDG2-transform portion No. 4 bottles, 180 DEG C of heated sealed reaction 3min, complete hydrolysis reaction.
(6) HPLC separation and purification.Cooling reaction flask, adds the acetic acid solution in FDG2-transform portion kingpin, under N2 effect, transfers in No. 11 bottles of HPLC part.Start HPLC system, collect
18f-FDOPA component, is mixed with
18f-FDOPA injection liquid.
18the total generated time of F-FDOPA is less than 65min, and uncorrected putting productive rate is greater than 15%, and radiochemicsl purity is greater than 95%.
Although the present invention discloses as above with preferred embodiment, and is not used to limit scope of the invention process.The ordinary person of any this area, not departing from scope of invention, does some improvement, and namely every equal improvement done according to the present invention, should be scope of the present invention and contained.
Claims (7)
1. a small modules formula multifunction automatic PET pharmaceutical synthesis instrument, comprising:
Single FDG synthesis module, or two FDG synthesis modules and FDG1 module and FDG2 module of connecting, for completing separately FDG synthesis or completing two batches of FDG synthesis in combination continuously;
PET medicament production separation system, is connected with single FDG synthesis module, or second module in the FDG synthesis module of connecting with two and FDG2 model calling; And Controlling System, for connecting and controlling described FDG synthesis module, described PET medicament production separation system.
2. small modules formula multifunction automatic PET pharmaceutical synthesis instrument according to claim 1, it is characterized in that, described single FDG synthesis module comprises:
Heated reaction system, comprising:
Round bottom reaction tubes, the mouth of pipe is equipped with the sealing cover of band octal, and the first to the 6th hole is N
2sample under carrier band adds hand-hole, and seven apertures in the human head is FDG output of products hole, and octal is vacuum pump safety flack access aperture;
Aluminium sheet well heater, is placed in the bottom of described round bottom reaction tubes, for heating the bottom conversion zone of described round bottom reaction tubes; N is provided with near conversion zone
2refrigerating unit;
Sample adding system, comprising:
First to the 6th application of sample bottle (1-6), connects respectively and is used for input by N
2first group of 6 one-way valve of the sample of carrier band (V1 '-V6 '), and connect second group 6 one-way valve (V1-V6) being used for sample being outputted to described sealed reaction tube respectively;
Wherein, the sample of the first application of sample bottle (1) is at N
2the first one-way valve (V1) via second group under carrier band enters the 12 T-valve (V12), with trapping by accelerator-produced
18f
-sep-Pak QMA pillar, then import described round bottom reaction tubes by the 13 T-valve (V13), another outlet of the 13 T-valve (V13) connects
18o
-useless target Water Sproading bottle;
Wherein, the sample of the 6th application of sample bottle (6) is at N
2the tenth T-valve (V10) is output under carrier band; N
2or He gas transmission system, comprise the N connected successively
2or He source of the gas, total air valve, reducing valve, gas meter and related valve, N
2or He gas flows through first group of 6 one-way valve (V1 '-V6 ') and inputs to the described first to the 6th application of sample bottle (1-6), part N after decompression
2also flow into the 7th T-valve (V7) through anemometer and check valve, and enter reaction tubes further by the 8th one-way valve (V8), for mixed reaction solution, then export through the 9th one-way valve (V9);
FDG output of products system, comprises the seven apertures in the human head output tube and the related valve that insert also through sealing cover bottom described round bottom reaction tubes, reacts the FDG product of generation at N in described round bottom reaction tubes
2under carrier band, the 7th T-valve (V7) is outputted to through the 8th one-way valve (V8), again through the tenth T-valve (V10), by two Sep-Pak C-18 pillar guiding the 11 T-valve (V11), an outlet of T-valve (V11) is connected with waste liquid bottle, another outlet is connected with product-collecting bottle, between T-valve (V11) and product-collecting bottle, arrange aseptic filter membrane;
Vacuum pump system, comprises the 9th one-way valve (V9), safety flack and vacuum pump, and the pipeline through safety flack passes through the octal that the 9th one-way valve (V9) inserts the sealing cover of described round bottom reaction tubes.
3. small modules formula multifunction automatic PET pharmaceutical synthesis instrument according to claim 1, it is characterized in that, in the FDG synthesis module of described two series connection, the 11 T-valve (V11) be directly connected with product-collecting bottle in first FDG synthesis module (i.e. FDG1 module), connects with the tenth T-valve (V10) be connected with two Sep-Pak C18 pillar inlet pipes in second FDG synthesis module (i.e. FDG2 module).
4. small modules formula multifunction automatic PET pharmaceutical synthesis instrument according to claim 1, it is characterized in that: when described HPLC separation module is connected with FDG synthesis module, the outlet pipe of the 11 T-valve (V11) be directly connected with product-collecting bottle of described FDG synthesis module is connected to described PET medicament production separation module.
5. small modules formula multifunction automatic PET pharmaceutical synthesis instrument according to claim 1, it is characterized in that: described PET medicament production separation system is HPLC separation system or pillar separation system, wherein, HPLC separation system comprises product HPLC separation and purification post-heating and desolventizes system, can be used for the separation and purification of all PET medicines.
6. small modules formula multifunction automatic PET pharmaceutical synthesis instrument according to claim 1, is characterized in that: change described each FDG synthesis module, HPLC separation system and pipeline connecting mode, automatic production can comprise all of FDG
18f marks PET medicine.
7. small modules formula multifunction automatic PET pharmaceutical synthesis instrument according to claim 1, it is characterized in that: change control program, increase and decrease application of sample bottle number and change pipeline connecting mode and radioactive source condition under, described FDG1 module and FDG2 module can upgrade to respectively
11cH
3br synthesis module and
11c-methylates synthesis module, for
11cH
3i or
11cH
3br or
11cH
3-Triflate, conventional
11c-methylate medicine and
11the production of C-acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410521021.8A CN104262073B (en) | 2014-09-30 | 2014-09-30 | Small modules formula multifunction automatic18f labelling PET pharmaceutical synthesis instrument |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410521021.8A CN104262073B (en) | 2014-09-30 | 2014-09-30 | Small modules formula multifunction automatic18f labelling PET pharmaceutical synthesis instrument |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104262073A true CN104262073A (en) | 2015-01-07 |
| CN104262073B CN104262073B (en) | 2016-08-17 |
Family
ID=52153695
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410521021.8A Active CN104262073B (en) | 2014-09-30 | 2014-09-30 | Small modules formula multifunction automatic18f labelling PET pharmaceutical synthesis instrument |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104262073B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105152960A (en) * | 2015-10-11 | 2015-12-16 | 北京脑重大疾病研究院 | An automatic preparation method and device for 18F-(2S, 4R)-4-fluoro-L-glutamine |
| CN106178594A (en) * | 2016-08-10 | 2016-12-07 | 周彤 | Repeatedly, Fast back-projection algorithm18the technique of F FDG and the valve system used |
| CN107118097A (en) * | 2016-02-25 | 2017-09-01 | 广东回旋医药科技股份有限公司 | 2-18F- fluoropropionic acids isomers, its synthetic method and its application |
| CN107474082A (en) * | 2017-08-11 | 2017-12-15 | 深圳市保健委员会办公室 | Double batch PET developers18F FDG pharmaceutical synthesis device and method |
| CN107501393A (en) * | 2017-09-13 | 2017-12-22 | 北京派特生物技术有限公司 | 18F labeled amino acid polypeptide drug synthetic methods and kit |
| CN108250260A (en) * | 2018-03-05 | 2018-07-06 | 广州市原子高科同位素医药有限公司 | 16α-[18F] fluoro- 17 beta estradiol automatic synthesis method |
| CN113353306A (en) * | 2021-06-07 | 2021-09-07 | 江苏华益科技有限公司 | Technetium [ alpha ], [ alpha ]99mTc]Automatic leaching, synthesizing and subpackaging method for marked medicines |
| CN113663621A (en) * | 2020-05-14 | 2021-11-19 | 益诺思生物技术海门有限公司 | A kind of89Zr medicine marking and purifying device and method |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1765911A (en) * | 2005-11-18 | 2006-05-03 | 南方医科大学南方医院 | 2- 18The synthesis technique of F-2-DDG |
| CN101104627A (en) * | 2007-07-20 | 2008-01-16 | 张锦明 | 18F-FDG automatization synthetic method and device |
| CN101648899A (en) * | 2009-09-15 | 2010-02-17 | 中国医学科学院北京协和医院 | New synthetic method of PET imaging agent L-5-<18>FETP |
| CN101798257A (en) * | 2010-03-04 | 2010-08-11 | 中山大学附属第一医院 | Automatic synthesis method of methylation reagent [11C] CH3Br |
| CN101830937A (en) * | 2009-03-12 | 2010-09-15 | 张锦明 | Visualized double-reaction tube fluorine-18 multifunctional automated synthesis module |
| CN101891687A (en) * | 2009-05-19 | 2010-11-24 | 中国医学科学院北京协和医院 | Method for synthesizing hypoxia imaging agent 18F-FMISO |
| 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 |
-
2014
- 2014-09-30 CN CN201410521021.8A patent/CN104262073B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1765911A (en) * | 2005-11-18 | 2006-05-03 | 南方医科大学南方医院 | 2- 18The synthesis technique of F-2-DDG |
| CN101104627A (en) * | 2007-07-20 | 2008-01-16 | 张锦明 | 18F-FDG automatization synthetic method and device |
| CN101830937A (en) * | 2009-03-12 | 2010-09-15 | 张锦明 | Visualized double-reaction tube fluorine-18 multifunctional automated synthesis module |
| CN101891687A (en) * | 2009-05-19 | 2010-11-24 | 中国医学科学院北京协和医院 | Method for synthesizing hypoxia imaging agent 18F-FMISO |
| CN101648899A (en) * | 2009-09-15 | 2010-02-17 | 中国医学科学院北京协和医院 | New synthetic method of PET imaging agent L-5-<18>FETP |
| CN101798257A (en) * | 2010-03-04 | 2010-08-11 | 中山大学附属第一医院 | Automatic synthesis method of methylation reagent [11C] CH3Br |
| 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 |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105152960A (en) * | 2015-10-11 | 2015-12-16 | 北京脑重大疾病研究院 | An automatic preparation method and device for 18F-(2S, 4R)-4-fluoro-L-glutamine |
| CN107118097A (en) * | 2016-02-25 | 2017-09-01 | 广东回旋医药科技股份有限公司 | 2-18F- fluoropropionic acids isomers, its synthetic method and its application |
| CN106178594A (en) * | 2016-08-10 | 2016-12-07 | 周彤 | Repeatedly, Fast back-projection algorithm18the technique of F FDG and the valve system used |
| CN107474082A (en) * | 2017-08-11 | 2017-12-15 | 深圳市保健委员会办公室 | Double batch PET developers18F FDG pharmaceutical synthesis device and method |
| CN107474082B (en) * | 2017-08-11 | 2020-07-17 | 深圳市保健委员会办公室 | Double-batch PET developer18F-FDG drug synthesis equipment and method |
| CN107501393A (en) * | 2017-09-13 | 2017-12-22 | 北京派特生物技术有限公司 | 18F labeled amino acid polypeptide drug synthetic methods and kit |
| CN108250260A (en) * | 2018-03-05 | 2018-07-06 | 广州市原子高科同位素医药有限公司 | 16α-[18F] fluoro- 17 beta estradiol automatic synthesis method |
| CN113663621A (en) * | 2020-05-14 | 2021-11-19 | 益诺思生物技术海门有限公司 | A kind of89Zr medicine marking and purifying device and method |
| CN113353306A (en) * | 2021-06-07 | 2021-09-07 | 江苏华益科技有限公司 | Technetium [ alpha ], [ alpha ]99mTc]Automatic leaching, synthesizing and subpackaging method for marked medicines |
| CN113353306B (en) * | 2021-06-07 | 2022-07-08 | 江苏华益科技有限公司 | Technetium [ alpha ], [ alpha ]99mTc]Automatic leaching, synthesizing and subpackaging method for marked medicines |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104262073B (en) | 2016-08-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104262073A (en) | Small modular multifunctional automatic 18F labelling PET (positron emission tomography) drug synthesizer | |
| CN100374453C (en) | 2-18F-2-deoxidized-D-glucose synthesis process | |
| JP6496726B2 (en) | Dual use cassette for synthesizing 18F labeling composition | |
| IL159260A (en) | Processes, compounds, kits and cartridges for the production of tracers labeled with f18 and uses thereof in positron emmision tomography | |
| CN105330586A (en) | Preparation method of Apremilast | |
| CN106866675B (en) | Positron emitting tracer, preparation method and applications | |
| WO2007132689A1 (en) | Process for production of radioactive fluorine-labeled organic compound | |
| CN104230613A (en) | Small modularized multifunctional automatic <11>C-marked PET (positron emission tomography) pharmaceutical synthesis instrument | |
| CN101939290A (en) | Process for production of radioactive-fluorine-labeled organic compound | |
| CN102867559B (en) | Automated synthesizer of <18>F-marked PET (positron emission tomograph)/CT (computerized tomograph) molecular image probe | |
| KR101487345B1 (en) | Cassette for handling apparatus of radioactive isotope, handling apparatus of the same and handling system of the same | |
| US9988336B2 (en) | Gaseous F-18 technologies | |
| US7482498B2 (en) | Device and process for nucleophilic fluorination | |
| CN102391318B (en) | Fluorine-18 fluorodeoxyglucose (18F-FDG) kit and application thereof in synthesis of positron emission tomography (PET) developer FDG | |
| CN107311877B (en) | A kind of positron medicine [18F] FDOPA novel processing step and its intermediate | |
| CN106902363A (en) | Radioactive composition, its single fraction preparation method and use | |
| CN112386949A (en) | Clinical single-tube fluorine-18 multifunctional module equipment and radiopharmaceutical synthesis process | |
| CN101597228B (en) | <11>C-acetate preparation method | |
| CN111333638A (en) | 18F-labeled isoquinolino pyridazinone compound and synthesis method and application thereof | |
| CN101168554A (en) | Method for preparing 18F-FLT | |
| Wang et al. | Automated synthesis of hypoxia imaging agent [18 F] FMISO based upon a modified Explora FDG 4 module | |
| CN113105432B (en) | Carbon-11 (C)11C) Radiopharmaceutical, preparation method and application thereof | |
| CN114656390A (en) | 18Synthesis method of F-labeled benzamide receptor developer | |
| Krasikova et al. | Asymmetric synthesis of 6-18 F-L-FDOPA using chiral Nickel (II) complexes | |
| US8624039B2 (en) | Method for preparing [18F]fallypride with low base concentration |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |