CN104307002A - Preparation method and applications of carrier-free [*I]MIBG suitable for clinical application - Google Patents

Preparation method and applications of carrier-free [*I]MIBG suitable for clinical application Download PDF

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CN104307002A
CN104307002A CN201410450278.9A CN201410450278A CN104307002A CN 104307002 A CN104307002 A CN 104307002A CN 201410450278 A CN201410450278 A CN 201410450278A CN 104307002 A CN104307002 A CN 104307002A
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mibg
free
carrier
preparation
formula
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CN104307002B (en
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王刚
陈志明
吴二明
汪洋
黄荷云
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Jiangsu Institute of Nuclear Medicine
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Jiangsu Institute of Nuclear Medicine
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Abstract

The invention provides a preparation method of carrier-free [*I]MIBG suitable for clinical application. The preparation method comprises the following steps: dissolving tin tributylbenzylguanidine in an alcoholic solvent, then adding the solvent into a phosphoric acid buffer solution, carrying out freeze-drying so as to obtain freeze-dried powder, adding the freeze-dried powder into a water solution containing *I ions, and then adding the water solution into an acidic buffer solution containing an oxidant to carry out reactions. Because the freezed-dried tin tributylbenzylguanidine powder cannot be dissolved in water, the unreacted tin tributylbenzylguanidine in the reaction liquid can be easily removed. The yield of [*I]MIBG is high. The labeling rate is high. The unreacted tin precursors and tin by-products can be easily and completely removed. The obtained [*I]MIBG does not contain any impurity. So the obtained carrier-free [*I]MIBG can be directly injected into human body, and is more suitable for clinical application.

Description

A kind of carrier-free of applicable clinical practice [ *i] preparation method of MIBG and application
Technical field
The invention belongs to radiopharmaceutical and nuclear medicine technology field, be specifically related to a kind of applicable clinical practice carrier-free [ *i] preparation method of MIBG and application.
Background technology
Meta iodobenzyl guanidine (MIBG) belongs to the analog of guanethidine, can concentrate in adrenal medulla, a kind of homologue of falling methylepinephrine neurotransmitter (NE), by means of NE, can be rich in orthosympathetic cell absorb, be a kind of carrier very valuable in Diagnosis and Treat myocardial abnormality and neuroendocrine tumour.Widely use in prior art with 131the MIBG of I labelling carries out the Diagnosis and Treat of video picture and neuroendocrine tumour.
Now external clinically [ 131i] MIBG majority passes through 131i and the MIBG method of isotopic Exchange obtains, containing a large amount of unlabelled MIBG carriers in the medicine that this method obtains, not only mark rate is on the low side, and a large amount of clinical trial confirms, compared to [* I] MIBG containing unlabelled MIBG carrier, containing unlabelled MIBG carrier or lower [* I] MIBG of unlabelled MIBG vector contg more effectively and side effect is less.That is in [* I] MIBG of labelling, unlabelled MIBG vector contg is lower, and [* I] MIBG can more effectively and side effect is less.
In order to improve the drug effect of [* I] MIBG and reduce possible side effect, [* I] MIBG for the unlabelled MIBG carrier do not contained or containing relatively low amount is referred to as carrier-free [* I] MIBG, described carrier-free [* I] MIBG because of mark rate high, and drug effect is high and side effect is little and studied widely and use.The method that Hunter seminar reports bonding tin group on synthetic resin prepares carrier-free [* I] MIBG (its synthetic route is shown in following formula), carrier-free [* I] the MIBG simple filtration that the method is obtained and separable, and without undesired impurities, but the method for synthetic resin and detection more complicated, be not suitable for the preparation of Routine Test Lab.
There was reported in prior art with the trimethyl silicon based benzyl guanidine in a position as precursor synthesizes the method for carrier-free [* I] MIBG, but the method synthesis step is various, carrier-free [* I] MIBG obtained is unstable, and decompose very fast at ambient temperature, make in medicine still containing a large amount of unlabelled MIBG carriers, carrier-free [* I] the MIBG drug effect for preparing is reduced and side effect increases, simultaneously free in solution 131i increases along with time lengthening, and 131i has larger toxicity, makes [* I] MIBG be not easy to transport, storage and use.And for example disclose a kind of with N in patent documentation US2011040119A1; N-bis-tertbutyloxycarbonyl; 3-tributyl tinbase benzyl guanidine is the method for precursor synthesis carrier-free [* I] MIBG; the method introduces BOC blocking group in 3-tributyl tinbase benzyl guanidine precursor; although mark rate is higher; but bring impurity in [* I] MIBG of labelling, [* I] MIBG prepared can not be injected directly in human body, be unfavorable for clinical practice.
Summary of the invention
For this reason, technical problem to be solved by this invention be prepared by method of the prior art [ *i] MIBG can not be injected directly into human body, is not suitable for clinical practice, and then provide a kind of applicable clinical practice carrier-free [ *i] preparation method of MIBG and application.
For solving the problems of the technologies described above, the invention provides a kind of applicable clinical practice carrier-free [ *i] preparation method of MIBG, comprise the steps:
(1) the tributyltin base benzyl guanidine shown in modus ponens A-I is dissolved in alcohols solvent, and to be added to appropriate pH value be that in the phosphate buffer of 3.5-8.0, lyophilization obtains freeze-dried powder;
(2) add in obtained freeze-drying powder and contain *the mixing of the aqueous solution of I ion, acidic buffer and oxidizing agent solution, react under room temperature 1.5-2.5 hour;
(3) add the step of excessive sodium pyrosulfite cessation reaction subsequently, obtain carrier-free shown in formula A-II [ *i] MIBG.
In described preparation method, also comprise by shown in obtained formula A-II carrier-free [ *i] MIBG carries out the step of separation and purification, namely to obtained carrier-free containing shown in formula A-II [ *i] add anion exchange resin in MIBG solution, collect the supernatant and also filter, obtain carrier-free shown in formula A-II [ *i] MIBG.
In described preparation method, described alcohols solvent is methanol or ethanol.
In described preparation method, the acetum of described acidic buffer to be concentration range be 80-120mmoL/L.
Preferably, the acetum of described acidic buffer to be concentration range be 100mmoL/L.
In described preparation method, the hydrogen peroxide solution of described oxidant to be concentration range be 80-120mmoL/L.
Preferably, the concentration range of described oxidant is the hydrogen peroxide solution of 100mmoL/L.
In described preparation method, describedly to contain *the radioactive intensity of the aqueous solution of I ion is 0.1 ~ 1.0mCi.
Preferably, describedly to contain *the radioactive intensity of the aqueous solution of I is 0.5mCi.
Described radiosiotope *the aqueous solution of I ion can be 123i, 124i, 125i or 131the aqueous solution of I ion.
In described preparation method, described anion exchange resin is 717 type anion exchange resin.
In described preparation method, carrier-free shown in formula A-II [ *i] MIBG carries out in the step of separation and purification, and described filtration step is adopt aperture to be that the thin film of 0.22 micron filters.
The invention provides a kind of prepared by above-mentioned method carrier-free [ *i] MIBG.
Present invention also offers a kind of described preparation method and prepare the purposes in radioactive marker and drug world.
Technique scheme of the present invention has the following advantages compared to existing technology:
(1) applicable clinical practice of the present invention carrier-free [ *i] preparation method of MIBG, become freeze-dried powder by be dissolved in by tributyltin base benzyl guanidine in alcohols solvent and to join lyophilization in appropriate phosphate buffer, then obtained freeze-drying powder is joined and contain *in the aqueous solution of I ion, add subsequently in oxidant and acidic buffer and react, because the freeze-dried powder of tributyltin base benzyl guanidine (stannum precursor) is water insoluble, therefore after completion of the reaction, unreacted tributyltin base benzyl guanidine in reactant liquor can be removed easily by filtering, obtain [ *i] not only yield is high for MIBG, and mark rate is high, and the impurity such as the stannum by-product of unreacted stannum precursor and reacted rear generation can be removed easily completely, free from foreign meter, the carrier-free that makes to prepare [ *i] MIBG can direct injection in human body, be more suitable for clinical practice;
(2) applicable clinical practice of the present invention carrier-free [ *i] preparation method of MIBG, carrier-free [ *i] to carry out the step of separation and purification simple, easy to operate for MIBG, can directly apply to clinical;
(3) applicable clinical practice of the present invention carrier-free [ *i] the preparation method step of MIBG is simple, and productive rate is high, and mark rate is high, free from foreign meter, can be widely used in preparing radiopharmaceutic field.
Accompanying drawing explanation
In order to make content of the present invention be more likely to be clearly understood, below according to a particular embodiment of the invention and by reference to the accompanying drawings, the present invention is further detailed explanation, wherein
Fig. 1 is the collection of illustrative plates of the radioactivity HPLC of the blank marks sample of the embodiment of the present invention 4;
Fig. 2 is the collection of illustrative plates of the ultraviolet HPLC of the blank marks sample of the embodiment of the present invention 4;
Fig. 3 be the embodiment of the present invention 4 carrier-free [ 131i] collection of illustrative plates of radioactivity HPLC of MIBG sample solution;
Fig. 4 be the embodiment of the present invention 4 carrier-free [ 131i] collection of illustrative plates of ultraviolet HPLC of MIBG sample solution.
Detailed description of the invention
Described tributyl tinbase benzyl guanidine crude drug in following embodiment of the present invention can select commercially available prod, also can record according to existing document and carry out routine preparation, such as, adopt method described in following equation to prepare:
(1) bicarbonate of the meta iodobenzyl guanidine shown in described formula a can be raw material for commercially available conventional products, also can with an iodine benzylamine hydrochloride for raw material carries out conventional preparation, concrete preparation process can prepare with reference to the synthetic method of the bicarbonate of the meta iodobenzyl guanidine shown in described formula a disclosed in patent documentation US2011040119A1, products obtained therefrom carries out nuclear-magnetism and MR detects, its 1h NMR (500M, CD 3oD) δ 4.34 (s, 2H), 7.10-7.14 (t, 1H), 7.34-7.36 (d, 1H), 7.63-7.65 (d, 1H), 7.69 (s, 1H), coincide with the bicarbonate standard diagram of described meta iodobenzyl guanidine;
(2) synthesis of 1-[4-(trialkyl stannyl) benzyl] guanidine shown in described formula A-I, the bicarbonate getting the meta iodobenzyl guanidine shown in described formula a of 500mg (1.48mmol) is dissolved in the solution of the DMSO of 10mL, add two (tributyl tin) mixing of 947mg (1.63mmol) subsequently, and entirety is dissolved in 1 of 30mL, in 4-dioxane, add the bi triphenyl phosphorus palladium chloride of 104mg (0.15mmol) subsequently, at control temperature 100 DEG C, constant temperature carries out the reaction of stille organotin to solution blackening, no longer deepen to solution colour, be spin-dried for obtained above-mentioned solution, get acetic acid ethyl dissolution be spin-dried for after residue, with lysate described in after washing, again be spin-dried for, get dissolve with methanol be again spin-dried for after residue, described lysate is washed subsequently with normal hexane, then dry, 1-[4-(trialkyl stannyl) benzyl] guanidine shown in described formula A-I adopts preparative scale chromatography to be separated, described chromatographic condition is: chromatographic column: C 18reversed phase chromatographic column, particle diameter 5um, pillar specification 4.6*250mm, eluting: be that mobile phase carries out gradient elution with methanol-water, when concrete elution program is 0-15min, the volume ratio of methanol-water is by 50%:50% → 100%:0, running temperature is 25 DEG C, flow velocity is 0.01L/min, determined wavelength is 230nm, collection appearance time is the effluent under 13-15min, collects the stream part containing 1-[4-(trialkyl stannyl) benzyl] guanidine shown in formula A-I, be separated to obtain weak yellow liquid, products obtained therefrom carries out nuclear-magnetism and MR detects, display 1h NMR (500M, CD3OD) δ 0.88-0.91 (m, 9H), 1.08-1.11 (m, 6H), 1.32-1.37 (m, 6H), 1.55-1.58 (m, 6H), 4.39 (s, 2H), 7.24-7.26 (m, 1H), 7.33-7.37 (m, 1H), 7.41 (m, 2H), MR [MH] +: 439, coincide with 1-[4-(trialkyl stannyl) benzyl] guanidine standard diagram, namely compound shown in described formula A-I is 1-[4-(trialkyl stannyl) benzyl] guanidine.Its purity 95% of further detection, productive rate is 48.3%.
Above-mentioned two (tributyl tin) can replace to two (tin trimethyl), two (tin triethyl) and two (tripropyl stannum) prepares 1-[4-(tributylestannyl) benzyl] guanidine, 1-[4-(triethylstannyl) benzyl] guanidine and 1-[4-(tripropyl stannyl) benzyl] guanidine respectively.
The synthetic route of the tributyl tinbase benzyl guanidine in the following embodiment of the present invention is as follows:
The syntheti c route of the following embodiment of the present invention is as follows:
In following each embodiment, the involved INSTRUMENT MODEL used comprises:
HPLC, model is waters sunfire, originates from the U.S.;
Radioactive activity measuring meter, model is CALIRAD ISOTOPE CALIBRATOR CRC-250, originates from VICTOREEN company, the U.S.;
γ-enumerator, model is γ-counter 2480, originates from PE company, the U.S.;
UV-detector 2487 originates from waters company;
Infrared spectrometer, model is IR Bruker TENSOR-27 type, originates from Germany;
Nuclear magnetic resonance analyser, model is Bruker Avance III 400, originates from Germany;
Mass spectrograph, model is SQ Detector2, originates from the U.S.;
Isotope detector, model is Radiomatic 610TR, originates from PE company.
Embodiment 1
The present embodiment preparation be applicable to clinical practice carrier-free [ 123i] method of MIBG is as follows:
Get that the 3-(tributyl tinbase) shown in described formula A-I-benzyl guanidine 100 μ g (0.228 μm of ol) joins in the methanol solvate of 150 μ L, the pH value above-mentioned mixed liquor being added to 130 μ L is in the sodium dihydrogen phosphate buffer of 3.5, then said mixture lyophilization is obtained freeze-dried powder, described lyophilization program is: said mixture is placed in subzero 40 DEG C of pre-freezes 6 hours, evacuation keeps 2 hours subsequently, described temperature is kept 2 hours after subzero 20 DEG C, again described temperature is kept 12 hours to subzero 10 DEG C, then described temperature to 10 DEG C is kept 2 hours, finally described temperature to 25 DEG C is kept 5 hours, take the dish out of the pot, obtain freeze-dried powder, subsequently to the Na of 1.0 mCi adding 0.7mL in obtained freeze-drying powder 123the solution of I, and the mixed liquor containing the hydrogen peroxide of 80mmoL/L acetum and 120mmoL/L adding 200 μ L, react 2h under normal temperature condition, use the sodium pyrosulfite cessation reaction of the 2mg/mL of 2ml subsequently, the carrier-free obtained in separation and purification above-mentioned steps [ 123i] MIBG, be specially: to obtained carrier-free containing shown in formula A-II [ 123i] add several 717 type anion exchange resin in MIBG solution, collect the supernatant and via hole diameter is the membrane filtration of 0.22 μm, obtain carrier-free shown in formula A-II [ 123i] MIBG.
The present embodiment prepare [ 123i] MIBG mark rate is 83%, radiochemical purity is 99%, and the residual quantity of stannum is lower than 1ppb.
Embodiment 2
The present embodiment preparation be applicable to clinical practice carrier-free [ 124i] method of MIBG is as follows:
Get that the 3-(tributyl tinbase) shown in described formula A-I-benzyl guanidine 40 μ g (0.091 μm of ol) joins in the alcohol solvent of 100 μ L, the pH value above-mentioned mixed liquor being added to 100 μ L is in the potassium dihydrogen phosphate buffer solution of 8.0, then said mixture lyophilization is obtained freeze-dried powder, described lyophilization program is: said mixture is placed in subzero 40 DEG C of pre-freezes 6 hours, evacuation keeps 2 hours subsequently, described temperature is kept 2 hours after subzero 20 DEG C, again described temperature is kept 12 hours to subzero 10 DEG C, then described temperature to 10 DEG C is kept 2 hours, finally described temperature to 25 DEG C is kept 5 hours, take the dish out of the pot, obtain freeze-dried powder, subsequently to the Na of 0.1 mCi adding 3mL in obtained freeze-drying powder 124the solution of I, and the mixed liquor containing the hydrogen peroxide of 120mmoL/L acetum and 80mmoL/L adding 100 μ L, react 2.5h under normal temperature condition, use the sodium pyrosulfite cessation reaction of the 3mg/mL of 0.5ml subsequently, the carrier-free obtained in separation and purification above-mentioned steps [ 124i] MIBG, be specially: to obtained carrier-free containing shown in formula A-II [ 124i] add several 717 type anion exchange resin in MIBG solution, collect the supernatant and via hole diameter is the membrane filtration of 0.22 μm, obtain carrier-free shown in formula A-II [ 124i] MIBG.
The present embodiment prepare [ 124i] MIBG mark rate is 81%, radiochemical purity is 99%, and the residual quantity of stannum is lower than 1ppb.
Embodiment 3
The present embodiment preparation be applicable to clinical practice carrier-free [ 125i] method of MIBG is as follows:
Get that the 3-(tributyl tinbase) shown in described formula A-I-benzyl guanidine 80 μ g (0.182 μm of ol) joins in the methanol solvate of 200 μ L, the pH value above-mentioned mixed liquor being added to 180 μ L is in the potassium dihydrogen phosphate buffer solution of 5.0, then said mixture lyophilization is obtained freeze-dried powder, described lyophilization program is: said mixture is placed in subzero 40 DEG C of pre-freezes 6 hours, evacuation keeps 2 hours subsequently, described temperature is kept 2 hours after subzero 20 DEG C, again described temperature is kept 12 hours to subzero 10 DEG C, then described temperature to 10 DEG C is kept 2 hours, finally described temperature to 25 DEG C is kept 5 hours, take the dish out of the pot, obtain freeze-dried powder, subsequently to the Na of 0.8mCi adding 0.5mL in obtained freeze-drying powder 125the solution of I, and add the mixed liquor containing the hydrogen peroxide of 100mmoL/L acetum and 100mmoL/L of 150 μ L, react 1.5h under normal temperature condition, use the sodium pyrosulfite cessation reaction of the 2mg/mL of 1.5ml subsequently, the carrier-free obtained in separation and purification above-mentioned steps [ 125i] MIBG, be specially: to obtained carrier-free containing shown in formula A-II [ 125i] add several 717 type anion exchange resin in MIBG solution, collect the supernatant and via hole diameter is the membrane filtration of 0.22 μm, obtain carrier-free shown in formula A-II [ 125i] MIBG.
The present embodiment prepare [ 125i] MIBG mark rate is 84%, radiochemical purity is 99%, and the residual quantity of stannum is lower than 1ppb.
Embodiment 4
The present embodiment preparation be applicable to clinical practice carrier-free [ 131i] method of MIBG is as follows:
Get that the 3-(tributyl tinbase) shown in described formula A-I-benzyl guanidine 50 μ g (0.114 μm of ol) joins in the methanol solvate of 100 μ L, the pH value above-mentioned mixed liquor being added to 100 μ L is in the potassium dihydrogen phosphate buffer solution of 6.5, then said mixture lyophilization is obtained freeze-dried powder, described lyophilization program is: said mixture is placed in subzero 40 DEG C of pre-freezes 6 hours, evacuation keeps 2 hours subsequently, described temperature is kept 2 hours after subzero 20 DEG C, again described temperature is kept 12 hours to subzero 10 DEG C, then described temperature to 10 DEG C is kept 2 hours, finally described temperature to 25 DEG C is kept 5 hours, take the dish out of the pot, obtain freeze-dried powder, subsequently to the Na of 0.5 mCi adding 0.5mL in obtained freeze-drying powder 131the solution of I, and the mixed liquor containing the hydrogen peroxide of 100mmoL/L acetum and 100mmoL/L adding 100 μ L, react 2h under normal temperature condition, use the sodium pyrosulfite cessation reaction of the 2mg/mL of 0.5ml subsequently, the carrier-free obtained in separation and purification above-mentioned steps [ 131i] MIBG, be specially: to obtained carrier-free containing shown in formula A-II [ 131i] add several 717 type anion exchange resin in MIBG solution, collect the supernatant and via hole diameter is the membrane filtration of 0.22 μm, obtain carrier-free shown in formula A-II [ 131i] MIBG.
Adopt respectively ultraviolet HPLC method and radioactivity HPLC method detect blank marks sample and above-mentioned preparation carrier-free [ 131i] sample solution of MIBG, described blank marks sample solution: 0.1-5mL's is the Na of 0.1-1.0mCi/mL containing radioactive concentration scope 131the mixed solution of I, concentration to be 1mg/mL sodium sulfate and pH be 6.5 phosphate buffer, described carrier-free [ 131i] the sample solution 0.1-5mL of MIBG be the present embodiment prepare carrier-free [ 131i] MIBG; The chromatographic condition of described HPLC is: waters sunfire series, C18 packed column, and specification is 150*4.6mm, particle diameter 5 μm; Mobile phase: NH 4cl (1mmol/l): NH 4oH (1 mol/l): CH 3oH=1:2:27; Coutroi velocity 1ml/min; Determined wavelength λ=254nm; Appearance time is RT=4.7min.The carrier-free of described blank marks sample and above-mentioned preparation [ 131i] testing conditions of sample solution of MIBG is identical.The carrier-free that utilizes fluorescent spectrometry to detect the present embodiment to prepare [ 131i] residual quantity of the stannum such as by-product of the stannum of unreacted stannum precursor and reacted rear generation in MIBG.
Carrier-free that the present embodiment obtains [ 131i] testing result of MIBG is as follows: the carrier-free that obtains in described blank marks sample and above-described embodiment [ 131i] the radioactivity HPLC collection of illustrative plates of sample solution of MIBG and ultraviolet HPLC collection of illustrative plates be shown in Fig. 1-Fig. 4 respectively, from figure, the present embodiment prepare [ 131i] MIBG mark rate reaches more than 80%, and be 82% by calculating its mark rate, radiochemical purity is 99%; The residual quantity utilizing fluorescent spectrometry detection to obtain stannum is lower than 1ppb.
Effect comparison example
Disclosed in patent documentation CN 103908684 A conventionally for labelling carrier-free [ *i] medicine box and preparation method thereof of MIBG, specific as follows: in the oxidant freeze-dried powder in described kit part B, to add the 0.1-50mCi of 0.1-5.0mL containing radiosiotope *mixing is dissolved in the aqueous solution of I ion, subsequently above-mentioned lysate is added in described kit part A and mixes, 8-12min is reacted under normal temperature condition, subsequently the freeze-dried powder in described kit C part is added in above-mentioned reactant liquor and mixes, react 8-12min under normal temperature condition, obtain labelling carrier-free [ *i] MIBG.Described in calculating [ *i] mark rate of MIBG is 82%, radiochemical purity is 87%, and the residual quantity recording stannum is about 10ppm.
As fully visible, the present invention prepare carrier-free [ *i] obtain in the mark rate of MIBG and prior art Patent Literature [ *i] mark rate of MIBG is suitable, but in the residual quantity of Impurity Sn, carrier-free prepared by the present invention [ *i] residual quantity of stannum of MIBG obtain in Patent Literature compared to existing technology [ *i] residual quantity of stannum of MIBG significantly reduces, illustrate carrier-free prepared by the present invention [ *i] MIBG can directly apply to clinical.
Obviously, above-described embodiment is only for clearly example being described, and the restriction not to embodiment.For those of ordinary skill in the field, can also make other changes in different forms on the basis of the above description.Here exhaustive without the need to also giving all embodiments.And thus the apparent change of extending out or variation be still among the protection domain of the invention.

Claims (10)

1. an applicable clinical practice carrier-free [ *i] preparation method of MIBG, it is characterized in that, comprise the steps:
(1) the tributyl tinbase benzyl guanidine shown in modus ponens A-I is dissolved in alcohols solvent, and to be added to appropriate pH value be that in the phosphate buffer of 3.5-8.0, lyophilization obtains freeze-dried powder;
(2) add in obtained freeze-drying powder and contain *the mixing of the aqueous solution of I ion, acidic buffer and oxidizing agent solution, react under room temperature 1.5-2.5 hour;
(3) add the step of excessive sodium pyrosulfite cessation reaction subsequently, obtain carrier-free [* I] MIBG shown in formula A-II;
2. preparation method according to claim 1, it is characterized in that, also comprise the step of carrier-free [* I] MIBG shown in obtained formula A-II being carried out separation and purification, namely anion exchange resin is added to obtained containing in carrier-free [* I] the MIBG solution shown in formula A-II, collect the supernatant and filter, obtaining carrier-free [* I] MIBG shown in formula A-II.
3. preparation method according to claim 1 and 2, is characterized in that, described alcohols solvent is methanol or ethanol.
4. according to the arbitrary described preparation method of claim 1-3, it is characterized in that, the acetum of described acidic buffer to be concentration range be 80-120mmoL/L.
5. according to the arbitrary described preparation method of claim 1-4, it is characterized in that, the hydrogen peroxide solution of described oxidant to be concentration range be 80-120mmoL/L.
6. according to the arbitrary described preparation method of claim 1-5, it is characterized in that, the radioactive intensity of the described aqueous solution containing * I ion is 0.1 ~ 1.0mCi.
7., according to the arbitrary described preparation method of claim 2-6, it is characterized in that, described anion exchange resin is 717 type anion exchange resin.
8. according to the arbitrary described preparation method of claim 2-7, it is characterized in that, carry out in the step of separation and purification at carrier-free [* I] MIBG shown in formula A-II, described filtration step is adopt aperture to be that the thin film of 0.22 micron filters.
9. according to carrier-free [* I] MIBG that the arbitrary described method of claim 1-8 prepares.
10. the arbitrary described preparation method of claim 1-8 is preparing the purposes in radioactive marker and drug world.
CN201410450278.9A 2014-09-04 2014-09-04 A kind of carrier-free of suitable clinical practice [*I] MIBG preparation method and application Expired - Fee Related CN104307002B (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106187824A (en) * 2016-07-15 2016-12-07 江苏省原子医学研究所 A kind of131the preparation method of the meta iodobenzyl guanidine of I labelling
CN107624072A (en) * 2015-05-22 2018-01-23 通用电气健康护理有限公司 Risk stratification

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103908684B (en) * 2014-01-24 2017-02-15 江苏省原子医学研究所 Drug box for labeling carrier-free [＜*＞I] metaiodobenzylguanidine (MIBG) and preparation method thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107624072A (en) * 2015-05-22 2018-01-23 通用电气健康护理有限公司 Risk stratification
CN106187824A (en) * 2016-07-15 2016-12-07 江苏省原子医学研究所 A kind of131the preparation method of the meta iodobenzyl guanidine of I labelling

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