CN110204484A - It is a kind of18The fluorine pyridinecarboxylic glycine and its preparation method and application of F label - Google Patents
It is a kind of18The fluorine pyridinecarboxylic glycine and its preparation method and application of F label Download PDFInfo
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- CN110204484A CN110204484A CN201910541072.XA CN201910541072A CN110204484A CN 110204484 A CN110204484 A CN 110204484A CN 201910541072 A CN201910541072 A CN 201910541072A CN 110204484 A CN110204484 A CN 110204484A
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- pyridinecarboxylic
- glycine
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- formylglycine
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- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
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- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0455—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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- C—CHEMISTRY; METALLURGY
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- C07B2200/05—Isotopically modified compounds, e.g. labelled
Abstract
The present invention provides one kind18The fluorine pyridinecarboxylic glycine and its preparation method and application of F label, belongs to radiopharmaceutical chemistry technical field.It is provided by the invention18F label fluorine pyridinecarboxylic glycine be 6- [18F]-fluoro-3-pyridine formylglycine, 5- [18F]-fluoro- 2- pyridinecarboxylic glycine or 4- [18F]-fluoro- 2- pyridinecarboxylic glycine.It is provided by the invention18The fluorine pyridinecarboxylic glycine excellent in stability of F label, and biological property is good, does not have adverse effect to organism after decay, by internal distribution tests it is found that18The fluorine pyridinecarboxylic glycine of F label is mainly absorbed by kidney, and is excreted rapidly, will18The fluorine pyridinecarboxylic glycine of F label is injected in Mice Body after 10min, and almost all is discharged into bladder, provided by the invention18The fluorine pyridinecarboxylic glycine of F label is highly beneficial particularly with the renal functional evaluation of renal lesions.
Description
Technical field
The present invention relates to radiopharmaceutical chemistry technical fields, more particularly to one kind18The fluorine pyridinecarboxylic glycine of F label
And its preparation method and application.
Background technique
Positron emission tomography (PET) technology is the important means to be diagnosed the illness based on molecular level, since its is good
The advantages such as good spatial resolution and quantitative analysis have obtained clinical and scientific research extensive use and affirmative.But core is cured at present
The equipment that field images urinary system remains on SPECT, and main imaging agent is still99mTc-DTPA and99mTc-MAG3。99mFor Tc-DTPA due to being almost all discharged via glomerulus from blood plasma, main function is clinical assays kidney
Glomerular filtration rate (GFR), but since the limitation of SPECT picture reproducer makes clinic not be very quasi- during measuring GFR
Really, a portion is the reason is that delineate double kidney ROI manually not accurate enough due to clinical, furthermore is due to by background and Kidney depth
X-ray detection X is influenced with surrounding tissue, these factors to be influenced in various degree in the double kidney GFR of clinical Accurate Determining.And
And it is injecting99mKidney imaging aspect after Tc-DTPA, due to99mThe uptake ratio of Tc-DTPA is only the 20% of injection measurement, is caused
Lower kidney/background ratio, this is particularly disadvantageous for the imaging of the kidneys of patients of advanced stage renal insufficiency.Another kind imaging
Agent99mTc-MAG3 is current clinical most common tubular secretion type imaging agent, and it is about 50% that kidney, which extracts score, compared to99mTc-DTPA has higher kidney/background ratio, to obtain higher-quality kidney image, is particularly suited for baby and kidney
The poor patient of function, clinic are mainly used for measuring kidney effective plasma flow (ERPF).But99mTc-MAG3 with131I-OIH is in kidney
Kidney image similar, that high quality can not be obtained in terms of dirty imaging.Therefore, the above uses the SPECT of corresponding imaging medicament
No matter technology is all incomparable in image quality or in terms of accurate quantification analysis compared with PET/CT.Based on above-mentioned
Reason promotes many domestic and international experts and scholars to be devoted to research and develop a kind of novel and biological property kidney PET/CT is suitble to sweep
The imaging agent retouched, in the hope of the deficiency for replacing traditional picture reproducer and imaging agent to image kidney, then15O-H2O、13N-NH3、82Rb-Rb1、62CuCu(II)pyruvaldehydebis-(N-4-methylthiosemicarbazonato)、62Cu-Cu(II)
ethylglyoxal bis(thiosemicarbazone)、68Ga-Ga-ethylenediaminetetraaceticacid、55Co-Co-ethylenediaminetetraacetic acid and18The pet imaging agents such as F-NaF are applied in succession, still
All it is not applied to really clinical be patient service always these imaging agent half-life shorts or due to involving great expense etc..In recent years
Vibhudutta Awasthi et al. has developed a kind of novel kidney imaging agent p-18F-fluorohippurate(18F-PFH),
This imaging agent biological characteristics are ideal, are almost discharged by urinary system, with131I-OIH is compared and is shown higher kidney
Dirty/background ratio, and be metabolized without liver biliary system, the intake of remaining tissue organ is lower in addition to kidney, kidney imaging effect
Fruit is rather ideal, still18F-PFH synthesis step is cumbersome and the time is long, and yield is caused to be declined.Based on the studies above achievement
VibhuduttaAwasthi et al. has developed the similar imaging agent of another structure again18F-CNPFH, compared to18F-PFH synthesis
Step is relatively easy, but since there are metabolic events in liver biliary system for the imaging agent, so that background phase around kidney
To higher, imaging results are not highly desirable.
Summary of the invention
The purpose of the present invention is to provide one kind18The fluorine pyridinecarboxylic glycine and its preparation method and application of F label, this
What invention provided18The fluorine pyridinecarboxylic glycine of F label has excellent in stability, and biological property is good, and kidney uptake ratio is high, generation
Thank to fast advantage.
In order to achieve the above-mentioned object of the invention, the present invention the following technical schemes are provided:
The present invention provides one kind18The fluorine pyridinecarboxylic glycine of F label, it is described18The sweet ammonia of fluorine pyridinecarboxylic of F label
Acid be 6- [18F]-fluoro-3-pyridine formylglycine, 4- [18F]-fluoro- 2- pyridinecarboxylic glycine or 5- [18F]-fluoro- 2- pyridine
Formylglycine.
The present invention also provides described in a kind of above-mentioned technical proposal18The preparation side of the fluorine pyridinecarboxylic glycine of F label
Method includes the following steps:
(1) by bromopyridine formylglycine ester, solvent and [18F]-Source mixing, carries out necleophilic reaction, after purified, obtains18F- fluorine pyridinecarboxylic glycinate；Described [18F]-Contain in source [18F]-And catalyst；The bromopyridine formylglycine ester is
The bromo- 3- pyridinecarboxylic glycinate of 6-, 5- bromo-2-pyridyl formylglycine ester or 4- bromo-2-pyridyl formylglycine ester；
It (2) will be described18F- fluorine pyridinecarboxylic glycinate is mixed with sodium hydroxide solution, reaction is hydrolyzed, then mistake
Acid ion exchanges pillar, then filters through sterilised membrane filter, obtains in the solution18The fluorine pyridinecarboxylic glycine of F label.
Preferably, ester group is carbomethoxy, ethoxycarbonyl, propyl ester base, isopropyl ester group, fourth in the bromopyridine formylglycine ester
Ester group, tert-butyl ester base, isobutyl ester group or carbobenzoxy group.
Preferably, the catalyst includes phase transfer catalyst and base catalyst.
Preferably, the phase transfer catalyst is K222 or TBAHCO3。
Preferably, the base catalyst is K2CO3、KHCO3、K2(COO)2Or Cs2CO3。
Preferably, the temperature of the necleophilic reaction is 90 DEG C~150 DEG C, and the time is 5min~30min.
Preferably, the purifying is liquid chromatography purification.
The present invention also provides described in above-mentioned technical proposal18The fluorine pyridinecarboxylic glycine of F label is aobvious as PET/CT
As the application of agent.
Preferably, described18The fluorine pyridinecarboxylic glycine of F label is used as PET/CT renal imaging agent.
The present invention provides one kind18The fluorine pyridinecarboxylic glycine of F label, it is described18The sweet ammonia of fluorine pyridinecarboxylic of F label
Acid be 6- [18F]-fluoro-3-pyridine formylglycine, 5- [18F]-fluoro- 2- pyridinecarboxylic glycine or 4- [18F]-fluoro- 2- pyridine
Formylglycine.It is provided by the invention18The fluorine pyridinecarboxylic glycine excellent in stability of F label, it is activation after placing 120min
Purity is learned still 95% or more, and biological property is good, does not have adverse effect to organism after decay, passes through internal distribution tests
It is found that18The fluorine pyridinecarboxylic glycine of F label is mainly absorbed by kidney, and is excreted rapidly, will18The fluorine pyridine of F label
Formylglycine is injected in Mice Body after 10min, and almost all is discharged into bladder, can be used as PET/CT renal imaging agent, is realized
The renal functional imaging of PET, it is therefore, provided by the invention18The fluorine pyridinecarboxylic glycine of F label is particularly with renal lesions
It is highly beneficial that Renal function in early period damages initial stage.
Detailed description of the invention
Fig. 1 be 6- [19F]-fluoro-3-pyridine formylglycine ultraviolet peak figure；
Fig. 2 be 6- [18F]-fluoro-3-pyridine formylglycine radiation peak figure；
Fig. 3 be 6- [18F]-fluoro-3-pyridine formylglycine TLC spectrogram；
Fig. 4 be precursor compound 6- [18F]-fluoro-3-pyridine formylglycine methyl esters preparative HPLC separate tomographic map
Spectrum；
Fig. 5 be injection 6- [18F] healthy SD rat after-fluoro-3-pyridine formylglycine injection 30min urine
HPLC spectrogram；
Fig. 6 is 4 gained PET/CT of application examples imaging figure；
Fig. 7 is the when m- activity curve figure of the double kidneys of the gained of application examples 4.
Specific embodiment
The present invention provides one kind18The fluorine pyridinecarboxylic glycine of F label, it is described18The sweet ammonia of fluorine pyridinecarboxylic of F label
Acid be 6- [18F]-fluoro-3-pyridine formylglycine, 5- [18F]-fluoro- 2- pyridinecarboxylic glycine or 4- [18F]-fluoro- 2- pyridine
Formylglycine；The 6- [18F]-fluoro-3-pyridine formylglycine structure as shown in formula I, the 5- [18F]-fluoro- 2- pyrrole
The structure of pyridine formylglycine as shown in formula II, the 4- [18F]-fluoro- 2- pyridinecarboxylic glycine structure as shown in formula III；
The present invention also provides described in a kind of above-mentioned technical proposal18The preparation side of the fluorine pyridinecarboxylic glycine of F label
Method includes the following steps:
(1) by bromopyridine formylglycine ester, solvent and [18F]-Source mixing, carries out necleophilic reaction, after purified, obtains18F- fluorine pyridinecarboxylic glycinate；Described [18F]-Contain in source [18F]-And catalyst；The bromopyridine formylglycine ester is
The bromo- 3- pyridinecarboxylic glycinate of 6-, 5- bromo-2-pyridyl formylglycine ester or 4- bromo-2-pyridyl formylglycine ester；
It (2) will be described18F- fluorine pyridinecarboxylic glycinate is mixed with sodium hydroxide solution, reaction is hydrolyzed, then mistake
Acid ion exchanges pillar, then filters through sterilised membrane filter, obtains in the solution18The fluorine pyridinecarboxylic glycine of F label.
Preparation method provided by the present invention is raw materials used to be easy to get, and obtained by this method18The fluorine pyridinecarboxylic of F label
The advantage that glycine has chemical purity high, and simple process, it is easy to operate, it conventional multi-functional synthesis model can be used to realize it certainly
Dynamicization preparation.
The present invention by bromopyridine formylglycine ester, solvent and [18F]-Source mixing, carries out necleophilic reaction, after purified, obtains
It arrives18F- fluorine pyridinecarboxylic glycinate；Described [18F]-Contain in source [18F]-And catalyst；The bromopyridine formylglycine ester
For the bromo- 3- pyridinecarboxylic glycinate of 6-, 5- bromo-2-pyridyl formylglycine ester or 4- bromo-2-pyridyl formylglycine ester.
In the present invention, in the bromopyridine formylglycine ester ester group be preferably carbomethoxy, it is ethoxycarbonyl, propyl ester base, different
Propyl ester base, butyl ester base, tert-butyl ester base, isobutyl ester group or carbobenzoxy group.
The present invention is not particularly limited the source of the bromopyridine formylglycine ester, can be self-control or purchase；?
In the embodiment of the present invention, the bromopyridine formylglycine ester is preferably made by the steps to obtain:
By the activated carboxylic of Bromopicolinic acid, activation Bromopicolinic acid is obtained；The Bromopicolinic acid is the bromo- 3- pyridine of 6-
Formic acid, 5- bromo-2-pyridyl formic acid or 4- bromo-2-pyridyl formic acid；
The activation Bromopicolinic acid and glycinate or glycine esters hydrochloride are subjected to acylation reaction, obtain bromine pyrrole
Pyridine formylglycine ester.
The activated carboxylic of Bromopicolinic acid is obtained activation Bromopicolinic acid by the present invention；The Bromopicolinic acid is that 6- is bromo-
Acidum nicotinicum (No. CAS are as follows: 6311-35-9), 5- bromo-2-pyridyl formic acid (No. CAS are as follows: 30766-11-1) or the bromo- 2- pyrrole of 4-
Pyridine formic acid (No. CAS are as follows: 30766-03-1).
The present invention is not particularly limited the method for the activation, using activated carboxylic method commonly used in the art.
In embodiments of the present invention, the method for the activation preferably includes following steps: by Bromopicolinic acid, N, N- dicyclohexyl carbon two
After imines, 4-dimethylaminopyridine and solvent mixing, priming reaction is carried out, obtains activation Bromopicolinic acid；The bromopyridine first
Acid is the bromo- acidum nicotinicum of 6-, 5- bromo-2-pyridyl formic acid or 4- bromo-2-pyridyl formic acid.
In the present invention, the N, N- dicyclohexylcarbodiimide are carboxyl activator, and 4-dimethylaminopyridine is alkalinity
Catalyst, by the activated carboxylic of Bromopicolinic acid, makes it that can carry out acylation reaction in subsequent step in activation process.At this
In invention, when Bromopicolinic acid is the bromo- acidum nicotinicum of 6-, products therefrom be 6- [18F]-fluoro-3-pyridine formylglycine,
The Bromopicolinic acid be 5- bromo-2-pyridyl formic acid when, products therefrom be 5- [18F]-fluoro- 2- pyridinecarboxylic glycine, the pyrrole
Pyridine formic acid be 4- bromo-2-pyridyl formic acid when, products therefrom be 4- [18F]-fluoro- 2- pyridinecarboxylic glycine.
In embodiments of the present invention, solvent for use is preferably methylene chloride in the step of priming reaction, the dichloro
Methane is preferably anhydrous methylene chloride；The present invention is not particularly limited the dosage of the solvent, in embodiments of the present invention, institute
The amount ratio for stating Bromopicolinic acid and the solvent is preferably 1g:20mL.
In embodiments of the present invention, preferably -10~10 DEG C of the temperature of the priming reaction, further preferably -5~5
DEG C, the time is preferably 15~60min, further preferably 30~35min.
In embodiments of the present invention, the Bromopicolinic acid, N, N- dicyclohexylcarbodiimide and 4-dimethylaminopyridine
Molar ratio be preferably 1:1.2:0.6.
In embodiments of the present invention, after the completion of the activation, preferably reaction solution obtained by the activation is directly used in subsequent
Step.
After obtaining activation Bromopicolinic acid, the present invention is by the activation Bromopicolinic acid and glycinate or glycine esters
Hydrochloride carries out acylation reaction, obtains bromopyridine formylglycine ester.
In the present invention, when the activation Bromopicolinic acid and glycinate carry out acylation reaction, be particularly preferred as by
It is added dropwise in the activation Bromopicolinic acid after glycinate and solvent mixing, carries out acylation reaction, it is sweet to obtain bromopyridine formyl
Propylhomoserin ester.
In the present invention, the glycinate is preferably glycine methyl ester, glycine ethyl ester, glycine propyl ester, glycine
At least one of isopropyl ester, glycine butyl ester, tert-butyl glycinate, glycine isobutyl ester and glycine benzyl ester；The bromine pyrrole
The type of pyridine formylglycine ester is the type of corresponding glycinate, such as when glycinate is glycine methyl ester, the bromine pyrrole
Pyridine formylglycine ester is bromopyridine formylglycine methyl esters.
In the present invention, when the activation Bromopicolinic acid and glycine esters hydrochloride carry out acylation reaction, specifically
It is added dropwise in the activation Bromopicolinic acid after preferably mixing glycine esters hydrochloride, triethylamine and solvent, carries out acyl
Change reaction, obtains bromopyridine formylglycine ester.In the present invention, during the acylation reaction, triethylamine is as alkali in
With the hydrochloride in glycine esters hydrochloride Starting material, acylation reaction occurs for obtained glycinate and activation Bromopicolinic acid,
Generate bromopyridine formylglycine ester.
In the present invention, the glycine esters hydrochloride is preferably glycine methyl ester hydrochloride, glycine ethyl ester hydrochloric acid
It is salt, glycine propyl ester hydrochloride, glycine isopropyl ester hydrochloride, glycine butyl ester hydrochloride, glycine tert-butyl hydrochloride, sweet
At least one of propylhomoserin isobutyl ester hydrochloride and glycine benzyl hydrochloride；The type of the bromopyridine formylglycine ester is
The type of the ester of corresponding glycine esters hydrochloride, it is described such as when glycine esters hydrochloride is glycine methyl ester hydrochloride
Bromopyridine formylglycine ester is bromopyridine formylglycine methyl esters.
In the present invention, solvent used in the step of acylation reaction is preferably methylene chloride, the methylene chloride
Preferably anhydrous methylene chloride；The present invention is not particularly limited the dosage of the solvent, in embodiments of the present invention, the bromine
The amount ratio of pyridine carboxylic acid and the solvent is preferably 1g:15mL.
In the present invention, the Bromopicolinic acid and the molar ratio of glycinate or corresponding glycine esters hydrochloride are excellent
It is selected as 1:1~1.8.
In the present invention, described when the activation Bromopicolinic acid and glycine esters hydrochloride carry out acylation reaction
The molar ratio of Bromopicolinic acid and triethylamine is preferably 1:1~1.8.
In the present invention, the mixed liquor of glycinate and solvent is added by the way of dropwise addition or glycine esters salt is added
The mixed liquor of hydrochlorate, triethylamine and solvent can avoid reaction and release big calorimetric.
In the present invention, the process of the dropwise addition, the temperature for preferably remaining activation Bromopicolinic acid is -10~10 DEG C, drop
After the completion of adding, gained reaction solution is warming up to room temperature, carries out acylation reaction；The present invention does not have special limit to the rate of the heating
It is fixed, room temperature can be reached, in embodiments of the present invention, the temperature of activation Bromopicolinic acid is preferably kept by low temperature water-bath
It is -10~10 DEG C, after being added dropwise to complete, removes low temperature water-bath, gained reaction solution is made to warm naturally to room temperature；The temperature of the room temperature
Preferably 20~35 DEG C.
In the present invention, the time of the acylation reaction is preferably 0.1~20h；The time of the acylation reaction preferably from
Reaction solution is warming up to room temperature Shi Jiqi.
In the present invention, it is preferred to, fully reacting whether complete using TLC (thin layer chromatography) verifying acylation reaction,
Then carry out subsequent step, it is on the contrary then the reaction was continued.
After the completion of acylation reaction, the present invention preferably filters reaction solution obtained by acylation reaction, then rotates gained filtrate
To 0.1~2mL, column chromatographic purifying is carried out, bromopyridine formylglycine ester is obtained；The filtering can will be insoluble in reaction solution
Property substance remove.
In the present invention, chromatographic column used in the column chromatographic purifying is preferably the silicagel column of 300~400 mesh；The column layer
The eluent of analysis purifying is preferably the mixed liquor of methylene chloride and methanol；The volume ratio of the methylene chloride and methanol is preferably
50:1。
In the present invention, the solvent in the nucleophilic reaction step is preferably dimethyl sulfoxide, acetonitrile, N, N- dimethyl methyl
Amide or tetrahydrofuran, more preferably dimethyl sulfoxide, the present invention is not particularly limited the dosage of the solvent, in the present invention
In embodiment, the amount ratio of the bromopyridine formylglycine ester and solvent is preferably 1~25mg:0.5~2.0mL.
In the present invention, the catalyst preferably includes phase transfer catalyst and base catalyst；The phase transfer catalyst
Preferably K222 (i.e. Kryptofix 2.2.2) or TBAHCO3(i.e. tetra-n-butyl ammonium hydrogen carbonate), the base catalyst are preferably
K2CO3、KHCO3、K2(COO)2Or Cs2CO3.The present invention to it is described [18F]-The preparation method in source is not particularly limited, using ability
Domain routine [18F]-The preparation method in source, in embodiments of the present invention, described [18F]-The preparation method in source preferably makes
With Sep Pak QMA column capture [18F]-Afterwards, it is eluted using the phase transfer catalyst of 0.5~3mL/base catalyst eluent,
It is preferred that then elution gained liquid heating removal solvent is added 1mL acetonitrile azeotropic and is evaporated by 1.5mL eluent, obtain [18F]-
Source；The mass ratio of phase transfer catalyst and base catalyst is preferably 17.7 in the phase transfer catalyst/base catalyst eluent:
4.1, solvent is acetonitrile and water, and the volume ratio of the acetonitrile and water is 10:1；Phase transfer catalyst/base catalyst described in 1.5mL
The quality of phase transfer catalyst is preferably 17.7mg in eluent.
In embodiments of the present invention, it is prepared using the phase transfer catalyst of 1.5mL/base catalyst eluent
[18F]-Source preferably needs 1~25mg bromopyridine formylglycine ester, more preferably preferably 10mg.
In the present invention, the temperature of the necleophilic reaction is preferably 90~150 DEG C, and more preferably 120~130 DEG C, the time
Preferably 5~30min, more preferably 10~20min.
After the completion of necleophilic reaction, the present invention preferably purifies reaction solution obtained by necleophilic reaction.
In the present invention, the purifying is preferably liquid chromatography purification.In the present invention, the liquid chromatography purification can incite somebody to action
Phase transfer catalyst in reaction system removes, and can also completely remove unreacted precursor, i.e. bromopyridine formylglycine
Ester.
Through liquid chromatography purification, contained18The eluent of F- fluorine pyridinecarboxylic glycinate, then solvent evaporated, obtains
It arrives18F- fluorine pyridinecarboxylic glycinate.
It obtains18After F- fluorine pyridinecarboxylic glycinate, the present invention will be described18F- fluorine pyridinecarboxylic glycinate and hydrogen-oxygen
Change sodium solution mixing, reaction is hydrolyzed, then peracidity ion exchange pillar (i.e. ICH-H column or IC-H column), then through sterile
Membrane filtration obtains in the solution18The fluorine pyridinecarboxylic glycine of F label, acquired solution are to contain18The fluorine pyridine of F label
The injection of formylglycine.
In the present invention, the concentration of the sodium hydroxide solution is preferably 1mol/L~4mol/L, more preferably 2mol/L；
In embodiments of the present invention, when the bromopyridine formylglycine ester is 10.0mg, the dosage of the sodium hydroxide solution is excellent
It is selected as 0.1~1mL.
In the present invention, the time of the hydrolysis is preferably 2min~10min, more preferably 5min；Temperature is preferred
For room temperature, the room temperature is preferably 10 DEG C~35 DEG C, more preferably 20 DEG C~25 DEG C.
After the completion of the hydrolysis, the present invention preferably mixes reaction solution obtained by hydrolysis with water, then peracidity
Ion exchange pillar (i.e. ICH-H column or IC-H column).In embodiments of the present invention, the IC-H column be purchase in
The ion chromatography SPE column of AlltechMaxi-Clean producer, filler are IC-H (i.e. the polystyrene-based strong resin of H-type).At this
In invention, the IC-H column can neutralize sodium hydroxide used in basic hydrolysis.
In embodiments of the present invention, the dosage of the water mixed with reaction solution obtained by the hydrolysis is preferably 1~10mL,
More preferably 3mL.In the present invention, the effect that water is added will generate18The fluorine pyridinecarboxylic glycine whole mistake of F label
IC-H column, and obtain debita spissitudo18The fluorine pyridinecarboxylic glycine injection of F label.
After peracidity ion exchange pillar, gained eluent is sterile filtered by the present invention, obtains in the solution18F mark
The fluorine pyridinecarboxylic glycine of note.In the present invention, it obtains18The fluorine pyridinecarboxylic glycine of F label is scattered in solution, should
Solution be containing18The injection of the fluorine pyridinecarboxylic glycine of F label, can be directly used as PET/CT imaging agent.
In the present invention, in the solution18The putting yield of the fluorine pyridinecarboxylic glycine of F label is 10%~25%.
The present invention also provides described in above-mentioned technical proposal18The fluorine pyridinecarboxylic glycine of F label is aobvious as PET/CT
As the application of agent.
In the present invention, described18The fluorine pyridinecarboxylic glycine of F label is used preferably as PET/CT renal imaging agent.
In the present invention, what preparation method described in above-mentioned technical proposal obtained contains18The note of the fluorine pyridinecarboxylic glycine of F label
PET/CT imaging agent can be directly used as by penetrating liquid.
Below with reference to embodiment to one kind provided by the invention18The fluorine pyridinecarboxylic glycine and preparation method thereof of F label
It is described in detail with application, but they cannot be interpreted as limiting the scope of the present invention.
Embodiment 1
By the bromo- acidum nicotinicum of 6- (1.00g, 4.95mmol), N, N- dicyclohexylcarbodiimide (1.22g,
5.94mmol), 4-dimethylaminopyridine (0.36g, 2.97mmol) and anhydrous methylene chloride (20mL) mixing, in ice-water bath (0
DEG C) under the conditions of after mixing evenly, react 30min, obtain containing activate the bromo- acidum nicotinicum of 6- reaction solution；
By triethylamine (0.82mL, 5.94mmol), glycine methyl ester hydrochloride (0.75g, 5.94mmol) and anhydrous dichloro
It after methane (15mL) mixing, is added dropwise in the reaction solution of the bromo- acidum nicotinicum of 6- containing activation, after being added dropwise, restores extremely
Room temperature (23 DEG C) continues to be stirred to react 20h, and TLC detects end of reaction, then filters, and gained filtrate is carried out vacuum rotary steam, so
Column chromatography is carried out using the silicagel column of 300~400 mesh as chromatographic column afterwards, and it is the mixed of methylene chloride and methanol that column, which chromatographs eluent used,
The volume ratio of conjunction liquid, methylene chloride and methanol is 50:1；Obtained eluent will be collected successively to be rotated and dried, obtained
0.98g pale yellow powder shape solid, the i.e. bromo- 3- pyridinecarboxylic glycine methyl ester of precursor compound 6-, yield 73.13%；Through
The molecular weight for crossing the high resolution mass spec measurement bromo- 3- pyridinecarboxylic glycine methyl ester of 6- is [M+H]=272.9883, Theoretical molecular
Amount is 273.00.
[18F]-K222 (17.7mg)/K of 1.5mL is used after the capture of Sep Pak QMA column2CO3(4.1mg) solution is (molten
Agent are as follows: volume ratio be 10:1 acetonitrile/water mixed solution) elution, by gained eluent be heated to 110 DEG C of azeotropic be evaporated remove it is molten
Agent, 1mL acetonitrile is then added, and azeotropic is evaporated again, obtain [18F]-Source；
By 370MBq [18F]-The dimethyl sulfoxide in source and the bromo- 3- pyridinecarboxylic glycine methyl ester of 0.8mL precursor compound 6-
Solution (containing precursor compound 10.0mg) mixing, heated sealed to 120 DEG C of reaction 15min；After reaction, using HPLC into
Row purifying, purifying chromatographic column used is C18 reversed-phase column, and mobile phase is acetonitrile and water, and the flow velocity of mobile phase is 3mL/min, purifying
Using gradient elution, the condition of gradient elution are as follows: water 90% (0~1min), 90%~20% (1~20min), 20% (20~
30min), the liquid that retention time is 14~16min is collected, after solvent is evaporated off, adds the NaOH that 0.5mL concentration is 2mol/L molten
Liquid, stand 5min after plus water 1.5mL be uniformly mixed, obtained after ICH-H column, gained eluent sterilised membrane filter 6- [18F]-fluoro-
3- pyridinecarboxylic glycine injection, pH value are 6.0~7.0, to carry out PET/CT imaging, the 6- that will be obtained suitable for animal
[18F]-fluoro-3-pyridine formylglycine injection activity concentration is adjusted to 37MBq/mL.
By product 6- [18F]-fluoro-3-pyridine formylglycine activity divided by it is used [18F]-The activity in source, obtains this reality
Putting yield is 20 ± 5% after applying the correction of example.
With the chemical purity and radiochemical purity of HPLC measurement injection, such as Fig. 1 and Fig. 2, Fig. 1 be 6- [19F]-fluoro- 3-
The ultraviolet peak of pyridinecarboxylic glycine, Fig. 2 be 6- [18F]-fluoro-3-pyridine formylglycine radiation peak, in order to further determine
Chemical purity further measures chemical purity using thin layer chromatography (TLC method), as a result as shown in figure 3, Fig. 4 is precursor chemical combination
Object 6- [18F]-fluoro-3-pyridine formylglycine methyl esters preparative HPLC separation chromatography map.By Fig. 1~4 it is found that intermediate
6-[18F]-fluoro-3-pyridine formylglycine methyl esters occur between 14min~16min radiate peak, retention time 2min, with 6
-19The retention time at the ultraviolet peak of F-3- pyridinecarboxylic glycine is close, illustrate product be target product 6- [18F]-fluoro-3-pyridine
Formylglycine.Measured through TLC method, the Rf value of injection be 0.6 (under the conditions of the TLC [18F]-Rf value less than 0.1), can
See that the radiochemical purity of injection is greater than 99%.
By 6- [18F]-fluoro-3-pyridine formylglycine injection is stored at room temperature, after label 0min, 30min, 60min,
120min carries out the measurement of HPLC radiochemicsl purity, the radiochemicsl purity of 30min, 60min, 90min and 120min be respectively 98%,
98%, 97% and 96%, be above 95%, illustrate 6- [18F]-fluoro-3-pyridine formylglycine has excellent stability.
To the tail vein of healthy SD rat injection 0.2mL 8.4MBq 6- [18F] injection of-fluoro-3-pyridine formylglycine
Liquid is collected rat urine, the urine being collected into is detected through HPLC, as a result as shown in figure 5, in spectrogram not after injecting 30min
There is new radiation peak, 6- in unique retention time and injection for radiating peak [18F]-fluoro-3-pyridine formylglycine phase
Together, it is seen that significant change does not occur for imaging agent in urine, has certain advantage as potential PET/CT renal imaging agent.
Embodiment 2
According to the method for embodiment 1, the bromo- acidum nicotinicum of raw material 6- is replaced with into 5- bromo-2-pyridyl formic acid, prepares 5-
[18F]-fluoro- 2- pyridinecarboxylic glycine.
According to the method for embodiment 1 test 5- [18F] after the correction of-fluoro- 2- pyridinecarboxylic glycine putting yield for 10 ±
3%.
Embodiment 3
According to the method for embodiment 1, the bromo- acidum nicotinicum of raw material 6- is replaced with into 4- bromo-2-pyridyl formic acid, prepares 4-
[18F]-fluoro- 2- pyridinecarboxylic glycine.
According to the method for embodiment 1 test 5- [18F] after the correction of-fluoro- 2- pyridinecarboxylic glycine putting yield for 13 ±
6%.
Application examples 1
Undue toxicity experiment:
4 groups of healthy ICR mouse, every group 10,6- after the injection decay of every mouse tail vein [18F]-fluoro-3-pyridine first
Acyl glycine injection (0.2mL) conventinal breeding 48 hours, observes mouse growth situation.
Mouse tail vein injection decay after 6- [18F] it observes 48 hours after-fluoro-3-pyridine formylglycine and after a week,
The without any adverse reactions and phenomena of mortality are observed after dissection, have no any organ damage.
Using identical method test 5- [18F]-fluoro- 2- pyridinecarboxylic glycine injection and 4- [18F]-fluoro- 2- pyridine
The undue toxicity of formylglycine injection, as a result with 6- [18F]-fluoro-3-pyridine formylglycine injection is similar, mouse without
Adverse reaction and the phenomena of mortality are observed after dissection, have no any organ damage.
These results suggest that 6- [18F]-fluoro-3-pyridine formylglycine injection, 5- [18F]-fluoro- 2- pyridinecarboxylic is sweet
Propylhomoserin injection and 4- [18F]-fluoro- 2- pyridinecarboxylic glycine injection to body nontoxicity, can be further used for grinding in vivo
Study carefully.
Application examples 2
The test of haemocyte Percentage bound and plasma protein binding rate, erythrocyte binding rate:
After 3 female sd inbred rats (200~220g), 3.8% chloraldurate intraperitoneal anesthesia, 200 μ L of tail vein injection is implemented
1 gained 6- of example [18F]-fluoro-3-pyridine formylglycine injection (radioactive activity 7.4MBq), take blood 2.5mL to set after 5min
In heparin test tube, centrifugation 5min and washed corpuscles and plasma specimen.The radioactivity of haemocyte and blood plasma, time are measured respectively
Haemocyte Percentage bound is obtained after correction and correction for attenuation is equal to (haemocyte radiocounting/whole blood radiocounting) × 100%, knot
Fruit is 29.8 ± 7.7%.
1mL plasma specimen is placed in super filter tube (molecule retention 30000), super filter tube is with the concentration of 500 μ L in advance
The PBS solution of the 6- fluoro-3-pyridine formylglycine of 5mg/mL is cleaned, and with the centrifugal force 45min of 1667g, collects ultrafiltration
Liquid.The ultrafiltrate of 50 μ L blood plasma and 50 μ L is taken to be placed in the counting of r- counter respectively, as a result through time adjustment and background correction.Then blood
It starches protein binding rate and is equal to (1- [ultrafiltrate counting/blood plasma counts]) × 100%, result is 37.6 ± 5.3%.
Using 5- [18F]-fluoro- 2- pyridinecarboxylic glycine injection and 4- [18F] injection of-fluoro- 2- pyridinecarboxylic glycine
When liquid carries out above-mentioned experiment, similar performance is shown.
Application examples 3
Vivo biodistribution distribution
6 groups of healthy SD rat, every group 3,1 gained 6- fluoro-3-pyridine formylglycine of tail vein injection 0.2mL embodiment
Injection (7.4MBq), after injection when 5min, 60min, break neck put to death, solution take blood, the heart, liver, lung, kidney, spleen, stomach, small intestine,
Large intestine, brain, muscle and bone etc. organize internal organs, the radiocounting of tissue or internal organs are weighed and measure respectively, after decay correction
The percentage injection dose rate (%ID/g) of per gram of tissue is calculated, the results are shown in Table 1.
It mainly absorbs through kidney after in injection injection rat body and excretes rapidly, in putting for 10min and 1h kidney
Penetrating property uptake ratio is respectively 1.00 ± 0.28%ID/g and 0.07 ± 0.04%ID/g, and hetero-organization internal organs intake is few, and with
The extension of time, except the radioactive uptake of each internal organs of bladder or tissue be substantially reduced, removed in blood it is very fast, 10min and
Radiocounting is respectively 0.35 ± 0.29%ID/g and 0.02 ± 0.007%ID/g after 1h.It is adjoint and carry out the radioactivity in urine
It is gradually dense poly-；Bone has slight radioactive uptake, but uptake values at any time without significant change prompt that defluorinate does not occur in vivo,
It should be the physiological accumulations of bone.
1 6- of table [18F]-fluoro-3-pyridine formylglycine is in intracorporal bio distribution result (%ID/g, the n of healthy SD rat
=3)
| Internal organs | 10min | 1h |
| Blood | 0.35±0.29 | 0.02±0.007 |
| The heart | 0.04±0.01 | 0.008±0.003 |
| Liver | 0.08±0.03 | 0.01±0.005 |
| Lung | 0.28±0.14 | 0.02±0.01 |
| Kidney | 1.00±0.28 | 0.07±0.04 |
| Spleen | 0.09±0.01 | 0.01±0.002 |
| Urine | 15.71±1.37 | 10.71±4.10 |
| Large intestine | 0.08±0.02 | 0.03±0.01 |
| Brain | 0.01±0.001 | 0.008±0.003 |
| Flesh | 0.03±0.01 | 0.01±0.001 |
| Bone | 0.10±0.05 | 0.05±0.006 |
Using 5- [18F]-fluoro- 2- pyridinecarboxylic glycine injection and 4- [18F] injection of-fluoro- 2- pyridinecarboxylic glycine
When liquid carries out above-mentioned experiment, similar performance is shown.
Application examples 4
PET/CT imaging test:
Healthy ICR mouse 3 after 2% isoflurane gas induced anesthesia, is fixed on the Minerve mouse of 37 DEG C of constant temperature
Animal capsule (MinerveV é t é rinaire, Esternay, France) in, to keep animal heat constant,
The isoflurane mixed gas inhalation anesthesia for giving animal 2L/min air and 2% simultaneously, by 1 gained of tail vein injection embodiment
6-[18F]-fluoro-3-pyridine formylglycine injection (0.2mL, 7.4MBq), dynamic acquisition is carried out at the same time.
Image reconstruction uses the 3D Ordered Subsets Expectation based on Monte Carlo system model
Maximization (OSEM) algorithm.A CT scan carried out to mouse after PET acquisition, bulb voltage 80kV, electric current 1mA,
576 projections, total scanning time 1h are acquired altogether.CT image reconstruction uses Feldkamp filter back-projection algorithm, and executes beam
Hardening correcting and annular artifact correction.Image analysis using PMOD software (PMOD Technologies LLC, Zurich,
Switzerland it) carries out, sketches out the area-of-interests such as kidney, bladder, left ventricle (Volume ofinterest, VOI), and
Make the when m- activity curve (TAC) of double kidneys.When m- activity curve such as Fig. 7 institute as shown in fig. 6, double kidneys is schemed in gained PET imaging
Show.
It will be appreciated from fig. 6 that injection imaging agent (6- [18F]-fluoro-3-pyridine formylglycine injection) after 1min, double kidneys are aobvious
Shadow is clear, there is relatively clear boundary, is initially displayed kidney essence, radioactivity is gradually dense poly- at bladder, increase with time periphery
Image fades, and radioactivity focuses on renal plevis position, and then renal plevis shadow is also obvious thin out, and double renal imaging agent are almost after 10min
All it is discharged into bladder.As shown in Figure 7, the time of curve to reach to peak value is about 1.25min, and radioactivity is fallen to needed for peak value half
Time be about 2.6min, illustrate 6- [18F]-fluoro-3-pyridine formylglycine can be quickly through kidney excretion, to organism
It damages small.
Using 5- [18F]-fluoro- 2- pyridinecarboxylic glycine injection and 4- [18F] injection of-fluoro- 2- pyridinecarboxylic glycine
When liquid carries out above-mentioned PET/CT imaging test, similar performance is shown.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of18The fluorine pyridinecarboxylic glycine of F label, which is characterized in that described18F label fluorine pyridinecarboxylic glycine be
6-[18F]-fluoro-3-pyridine formylglycine, 5- [18F]-fluoro- 2- pyridinecarboxylic glycine or 4- [18F]-fluoro- 2- pyridinecarboxylic
Glycine.
2. described in claim 118The preparation method of the fluorine pyridinecarboxylic glycine of F label, which is characterized in that including walking as follows
It is rapid:
(1) by bromopyridine formylglycine ester, solvent and [18F]-Source mixing, carries out necleophilic reaction, after purified, obtains18F- fluorine
Pyridinecarboxylic glycinate；Described [18F]-Contain in source [18F]-And catalyst；The bromopyridine formylglycine ester is that 6- is bromo-
3- pyridinecarboxylic glycinate, 5- bromo-2-pyridyl formylglycine ester or 4- bromo-2-pyridyl formylglycine ester；
It (2) will be described18F- fluorine pyridinecarboxylic glycinate is mixed with sodium hydroxide solution, reaction is hydrolyzed, then peracidity
Ion exchange pillar, then filtered through sterilised membrane filter, it obtains in the solution18The fluorine pyridinecarboxylic glycine of F label.
3. preparation method according to claim 2, which is characterized in that ester group is first in the bromopyridine formylglycine ester
Ester group, ethoxycarbonyl, propyl ester base, isopropyl ester group, butyl ester base, tert-butyl ester base, isobutyl ester group or carbobenzoxy group.
4. preparation method according to claim 2 or 3, which is characterized in that the catalyst include phase transfer catalyst and
Base catalyst.
5. the preparation method according to claim 4, which is characterized in that the phase transfer catalyst is K222 or TBAHCO3。
6. the preparation method according to claim 4, which is characterized in that the base catalyst is K2CO3、KHCO3、K2(COO)2
Or Cs2CO3。
7. preparation method according to claim 2, which is characterized in that the temperature of the necleophilic reaction is 90 DEG C~150 DEG C,
Time is 5min~30min.
8. preparation method according to claim 2, which is characterized in that the purifying is liquid chromatography purification.
9. described in claim 118Application of the fluorine pyridinecarboxylic glycine of F label as PET/CT imaging agent.
10. application according to claim 9, which is characterized in that described18The fluorine pyridinecarboxylic glycine conduct of F label
PET/CT renal imaging agent uses.
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| WO2020253824A1 (en) * | 2019-06-21 | 2020-12-24 | 山西医科大学第一医院 | 18f-labeled fluoropicolinylglycine, preparation method therefor and application thereof |
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| CN110204484B (en) * | 2019-06-21 | 2023-07-21 | 山西医科大学第一医院 | The method comprises the following steps of 18 F-labeled fluoropyridine formylglycine, and preparation method and application thereof |
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Non-Patent Citations (4)
| Title |
|---|
| GREGORY N. NKEPANG等: "Facile synthesis of para-[18F]fluorohippurate via iodonium ylide-mediated radiofluorination for PET renography", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
| JOSE L. IZQUIERDO-GARCIA等: "Identification of novel metabolomic biomarkers in an experimental model of septic acute kidney injury", 《AMERICAN JOURNAL OF PHYSIOL》 * |
| LATIFA RBAH-VIDAL等: "Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [18F]ICF01006，a highly promising melanoma PET tracer", 《EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING》 * |
| VIBHUDUTTA AWASTHI等: "Synthesis and In Vivo Evaluation of p-18F-Fluorohippurate as a New Radiopharmaceutical for Assessment of Renal Function by PET", 《THE JOURNAL OF NUCLEAR MEDICINE》 * |
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| WO2020253824A1 (en) * | 2019-06-21 | 2020-12-24 | 山西医科大学第一医院 | 18f-labeled fluoropicolinylglycine, preparation method therefor and application thereof |
| CN111362828A (en) * | 2020-03-30 | 2020-07-03 | 山西医科大学 | A kind of18F-labeled fluoropropionylated ornithine as well as preparation method and application thereof |
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