CN101723848A - Novel 18F labeled m-nitro benzoyl amino acids, preparation method and application thereof in tumor imaging - Google Patents

Novel 18F labeled m-nitro benzoyl amino acids, preparation method and application thereof in tumor imaging Download PDF

Info

Publication number
CN101723848A
CN101723848A CN200810167557A CN200810167557A CN101723848A CN 101723848 A CN101723848 A CN 101723848A CN 200810167557 A CN200810167557 A CN 200810167557A CN 200810167557 A CN200810167557 A CN 200810167557A CN 101723848 A CN101723848 A CN 101723848A
Authority
CN
China
Prior art keywords
group
formula
tumor
acetonitrile
water
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
Application number
CN200810167557A
Other languages
Chinese (zh)
Other versions
CN101723848B (en
Inventor
齐传民
乔雅丽
张淑婷
贺勇
刘航
李桂霞
许荆立
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beijing Normal University
Original Assignee
Beijing Normal University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Beijing Normal University filed Critical Beijing Normal University
Priority to CN200810167557.9A priority Critical patent/CN101723848B/en
Publication of CN101723848A publication Critical patent/CN101723848A/en
Application granted granted Critical
Publication of CN101723848B publication Critical patent/CN101723848B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Landscapes

  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

The invention relates to novel 18F labeled m-nitro benzoyl amino acid compounds, which is characterized in that the compounds simultaneously have a 3-fluorine 18-5-nitro benzoyl structure and an alpha-amino acid structure, and have substituent R1 which is positioned on an alpha site of carboxyl group and is hydrogen, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, benzyl group, 2-methylthio-ethyl group, carboxyethyl group, carboxypropyl group, phenyl or imidazole methyl group. The structures at two ends are directly connected through amido bond. The structure of the compounds is shown in a formula A. The compounds are simple to synthesize, high in uptake and slow to clear in tumor tissue, low in uptake or fast to clear in normal tissue and blood, high in the ratio of tumor to blood and the ratio of tumor to normal tissue and particularly high in the ratio of tumor to brain, so the compounds are high in degree of distinguishing tumor from brain background and long in stable time. The invention also relates to the application of the compounds serving as a PET tumor imaging agent.

Description

Novel 18F mark m-nitro benzoyl amino acids, preparation method and the application in tumor imaging
Technical field:
The present invention relates to a kind of novel 18F mark m-nitro benzoyl amino acids compounds and and as the application of the tumor developer of positron emission tomography (PET).
Background technology:
The early diagnosis of tumour is a big focus of current medical science, and positron emission tomography (PET) is subjected to very big attention as a kind of means of more and more popularizing, thereby the breakthrough of the early diagnosis of tumour depends on the exploitation of PET tumor developer.
Radionuclide 18F is suitable as the video picture nucleic of PET because of its good nucleic character very much.
The radiopharmaceuticals of at present most widely used emission positron is 18The F-deoxyglucose ( 18F-FDG), the research and the clinical diagnosis of tumour, coronary heart disease and neuropsychiatric disease have been widely used in.But because normal cerebral tissue is bigger to the intake of FDG, also there is higher FDG to absorb in nonneoplastic tissue and the inflammatory cell composition, may causes the false positive results of diagnosing tumor when causing FDG to be used for the brain tumor video picture because there being inflammation.And amino acid in the absorption of normal cerebral tissue seldom, therefore causes extensive interest.It is that tumor proliferation may cause that the amino acid accumulating level increases as the foundation of tumor developer, to provide protein biosynthetic elementary cell.In addition, though the amino acid derivative of some mark does not participate in proteinic synthetic, as long as but can be transported by the system that transports of tumor tissues, also can be used as developer, therefore some amino acid derivative through radioisotope labeling also might become tumor developer.
At present, have 18The amino acid of F mark is synthesized out, and demonstrates result preferably in biological assessment, as O-(2-[ 18F] fluoro ethyl)-L-tyrosine ([ 18F] FET), O-(3- 18F-fluoro propyl group)-L-tyrosine ([ 18F] FPT), shown 18F labeled amino acid derivative is as the potentiality of PET tumor developer.
Summary of the invention:
The first, the invention provides a kind of tumor uptake height, the good radioactivity of specificity 18F mark m-nitro benzoyl amino acids compounds.
This kind 18F for the structure of compound suc as formula A:
Formula A
It is characterized in that: an end has 3-fluorine 18-5-oil of mirbane formyl structure; The other end has the a-amino acid structure, there is substituent R to be positioned on the alpha site of carboxyl group, the other end has a-amino acid methyl esters structure, substituent R is positioned on the ester group α position, is hydrogen, methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, benzyl, 2-methylmercaptoethyl, propyloic, carboxylic propyl group, phenyl, imidazoles methyl.Two-end structure directly links to each other by amido linkage.
Its preparation mainly is divided into the synthetic and precursor compound of labelled precursor compound 18Two parts of F mark and aftertreatment.
Concrete steps are as follows:
One. synthesizing of labelled precursor compound (formula B)
Figure G2008101675579D0000021
Formula B
Synthetic route is suc as formula shown in the C:
Figure G2008101675579D0000022
Formula C
1) esterification of amino acid carboxyl protection (formula D)
Amino acid 0.02mol joins among the anhydrous methanol 20mL, after the ice bath cooling, slowly drips SOCl 22.1mL, keep the temperature of reaction system to be no more than 10 ℃ in the dropping process, after being added dropwise to complete back low temperature and keeping being warmed up to room temperature reaction behind the reaction 30min and spend the night, revolve excessive SOCl 2And methyl alcohol, obtain white solid, drying behind the ether thorough washing, and, obtain white solid and be the amino acid methyl ester hydrochloride with the mixed solvent recrystallization of dehydrated alcohol or dehydrated alcohol and anhydrous diethyl ether.Productive rate 70-80%.
Formula D
2) 3, synthetic (the formula E) of 5-dinitrobenzene formyl amino acid formyl amino acid methyl esters
After amino acid methyl ester hydrochloride 3mmol is dissolved in the 20mL methylene dichloride, triethylamine 0.42mL (3mmol) back stirring reaction 5min is heavily steamed in disposable adding, add 3,5-dinitrobenzoic acid 0.424 gram (2mmol) and HOBt (1-hydroxy benzo triazole) 0.298 gram (2.2mmol), after reaction mixture is cooled to 0 ℃, drip the dichloromethane solution 5mL of DCC 0.46 gram (2.2mmol), being warming up to room temperature reaction behind the continuation low-temp reaction 0.5h after dropwising spends the night, after TLC shows that reaction finishes, suction filtration is removed a large amount of white precipitate shape by product DCU of generation, organic phase is with water, saturated sodium bicarbonate aqueous solution, saturated sodium-chloride water solution washing back anhydrous sodium sulfate drying, revolve and obtain oily matter after desolvating, the silicagel column column chromatography, eluent (ethyl acetate: obtain light yellow or white solid sherwood oil=1: 3), productive rate about 60%.
Figure G2008101675579D0000032
Formula E
Two. the radio-labeling of precursor compound and aftertreatment:
1) radio-labeling of precursor compound (formula F)
18F -After being caught by anion column QMA, with containing 10mg K2.2.2 and 3mg K 2CO 3The 1mL acetonitrile and the mixed solution of 0.5mL water it is flushed in the reaction flask, the anhydrous acetonitrile that in reaction flask, adds 0.5mL, be heated to 100 ℃, constantly feed nitrogen, utilize acetonitrile and water azeotropic water removing, after treating solvent dried up, add the anhydrous acetonitrile of 0.5mL more respectively, repeat twice of this operation, precursor compound shown in the 5mg formula B is dissolved in anhydrous N, dinethylformamide solution is poured in the reaction flask, is warming up to 125 ℃ rapidly, keeps about this thermotonus 30min, stopped reaction, add about 10mL water reaction system is diluted, by Sep-Pak C18 post, filtrate collection (is not mainly participated in reacting in headpin again 18F -), and then with 10mL water washing pillar, will (guarantee and will not participate in reaction in filtrate collection to 2 bottle 18F -Thoroughly drip washing is clean), with nitrogen Sep-Pak C18 post is dried up, with 2mL acetonitrile washing C18 post, in filtrate collection to 3 bottle, obtain 18F marked product 3, entire reaction course need 30min approximately.
Figure G2008101675579D0000041
Formula F
2) hydrolysis of mark intermediate product (formula G)
Marker 3 is through HPLC (band radioactivity probe) separation and purification, after with nitrogen the acetonitrile in the solution being dried up, with a certain amount of lithium hydroxide hydrolysis, uses the hcl acidifying of a certain amount of 1mol/L again in the mixing solutions of water and methyl alcohol, obtains 18F is for product 4, and this process needs 30min approximately, adds the preparation time of marker 3, needs about 60min altogether.
Figure G2008101675579D0000042
Formula G
The second, the present invention is above-mentioned 18The amino acid derivative of F mark is as the application of PET tumor developer.
The present invention has following good characteristic:
1) is used among the present invention carry out 18F labelled precursor compound is synthetic easy, and raw material is cheap and easy to get.Mark total time is short, and effectively the radioactivity loss is few.
2) of the present invention 18The compound of F mark has the particularly good biological property of cerebral tumor video picture of suitable tumor imaging.Mainly contain following some:
2.1 compound of the present invention clearance rate in blood, muscle tissue and brain is very fast, higher initial picked-up is arranged in tumour and remove relatively slow, in other internal organs initial picked-up low or remove very fast, thereby can be after injection the short period reach period of the high ratio of tumour/background.Have experiment to be card:
Make by embodiment 1 18The acetonitrile solution of F tagged compound dries up acetonitrile with nitrogen, is that 8-10 μ Ci/0.1mL is as injection liquid with physiological saline with the product dilution again.Take out the injection liquid of three parts of 0.1mL, add 9.9mL physiological saline respectively, behind the mixing, from every part, take out 0.1mL respectively again, as standardized solution, measure its radiocounting in the time of the radiocounting of each tissue of mouse to be determined and internal organs, averaging is that 1%ID uses.
Kunming mouse is divided into five groups at random, 3 every group.From tail vein injection 18The injection liquid 0.1mL of F marked product (8-10 μ Ci), respectively at 5min, 15min after the injection, 30min, 60min, 120min each is organized the mouse sacrificed by decapitation, with its rapid dissection, get tissue and internal organs such as brain, the heart, liver, lung, kidney, back bone, muscle, small intestine, large intestine, spleen, blood, tumour, weigh after drying, and measure its radiocounting separately, and calculating the radioactive uptake %ID/g of its each tissue and internal organs, three groups of panel datas are got in each experiment.
R is that the compound experimental result of sec.-propyl is as shown in table 1 among the formula A:
Table 1 18Bio distribution data in the body of the lotus S180 knurl mouse of F marked product (R is the compound of sec.-propyl among the formula A) (%ID/g ± SD, n=3)
Table 1 data are through arrangement, obtain this compound each the time item tumour/healthy tissues unit mass radioactive activity ratio, as shown in table 2:
Table 2 18F marked product (R is the compound of sec.-propyl among the formula A) is at the intravital T/B ratio of lotus S180 knurl mouse
Figure G2008101675579D0000052
As can be seen from Table 2, the T/B ratio 5-30 of this compound divides rising rapidly, all reaches peak value and more stable in 30-60 divides after 30 minutes, slowly descends afterwards, and therefore, this compound divides the most suitable video picture during this period of time at 30-60.
2.2 compare with present technology, of the present invention 18The F tagged compound has novelty, is embodied in the remarkable advantages of some aspects of biological property, is exemplified below:
With the PET tumor developer that has very big application potential at present 18F-FET compares, and is of the present invention 18The F tagged compound has a clear superiority in the differentiation of tumour and healthy tissues.Have experiment to be card:
Undertaken by 2.1 identical implementation methods 18Distribute in the lotus S180 knurl mouse body of F-FET and test, experimental result is as shown in table 3:
Table 3 18Bio distribution data in the body of the lotus S180 knurl mouse of F-FET (%ID/g ± SD, n=3)
Figure G2008101675579D0000061
Contrast table 1 and table 3 are as can be seen, and be of the present invention 18F is for compound (compound 4a among the embodiment) ratio 18F-FET has the clearance rate of obviously high healthy tissues, and is of the present invention 18F can obtain higher tumour/background radiation ratio for compound (compound 4a among the embodiment) through the short period.
Obtain after sorting table 3 data 18The tumour of F-FET/healthy tissues ratio is as shown in table 4:
Table 4 18F-FET is at the intravital T/B ratio of lotus S180 knurl mouse
Figure G2008101675579D0000062
Contrast table 2 and table 4 are as can be seen, and be of the present invention 18F tagged compound (compound 4a among the embodiment) all is higher than at the every T/B ratio of 30-60min section 18F-FET corresponding T/B value, particularly tumour/brain peak value is 4 times of the latter especially.Though at 60-120min, 18F-FETF/B ratio is stabilized in the 30-60min level even also increases to some extent, but consider the size of whole body distribution speed, normal injection dosage and the characteristic that radiopharmaceuticals is lost by radioactive index decay rule, the best visualization time should be after injection 30-60min, and in this interval, of the present invention 18The every T/B ratio of F tagged compound is right 18F-FET has clear superiority, and this makes of the present invention 18The F tagged compound carries out tumor imaging particularly may obtain ratio during the cerebral tumor video picture 18The higher-quality image of F-FET.
2.3 experiment demonstrates of the present invention owing to distribute in the lotus S180 knurl mouse body 18F mark m-nitro benzoyl amino acids derivative is the bio distribution performance preferably; we have tentatively carried out the interior distribution research to lotus lotus neurospongioma mouse body; result and lotus S180 knurl mouse tumor/the background ratio variation tendency is similar; though the corresponding ratio of 5-15min is less; but 30-60min is very approaching; tumour/brain, tumour/blood, tumour/meat reach peak value 8.77,1.43 and 2.60 separately at 30-60min respectively, and after comparatively stable.As shown in table 5:
Table 5 18F marked product (R is the compound of sec.-propyl among the formula A) is at the intravital T/B ratio of lotus neurotic glioma mouse
To sum up, provided by the present invention 18The F tagged compound had compared with prior art both had good biological property, had the preparation characteristic of simple again.Have as the tumor developer potentiality of brain tumor imaging agent particularly.
Embodiment:
Below by embodiment the present invention is more clearly described, but the present invention is not limited to following examples.
Embodiment:
According to following steps preparations be that the R base be the compound of sec.-propyl among the formula A, comprise the synthetic and precursor compound of labelled precursor (R gets the compound of sec.-propyl among the formula B) 18F mark, two parts of hydrolysis.
1) labelled precursor (R gets the compound of sec.-propyl among the formula B) is synthetic
1.13-synthetic (the formula H) of methyl-2-aminobutyric acid methyl ester hydrochloride
3-methyl-2-aminobutyric acid (Xie Ansuan) 0.02mol joins among the anhydrous methanol 20mL, after the ice bath cooling, slowly drips SOCl 22.1mL, keep the temperature of reaction system to be no more than 10 ℃ in the dropping process, after being added dropwise to complete back low temperature and keeping being warmed up to room temperature reaction behind the reaction 30min and spend the night, revolve excessive SOCl 2And methyl alcohol, obtain white solid, drying behind the ether thorough washing, and, obtain white solid and be 3-methyl-2-aminobutyric acid methyl ester hydrochloride with the mixed solvent recrystallization of dehydrated alcohol or dehydrated alcohol and anhydrous diethyl ether.Productive rate 70-80%.m.p.：156-158℃；IR(KBr，cm -1)：v?3432，1740，1265。
Figure G2008101675579D0000072
Formula H
1.2 synthetic (the formula I) of 2-(3, the 5-nitro) benzoylamino-3 Methylbutanoic acid methyl esters
After the 3-methyl-2-aminobutyric acid methyl ester hydrochloride 0.504 gram (3mmol) is dissolved in the 20mL methylene dichloride, triethylamine 0.42mL (3mmol) back stirring reaction 5min is heavily steamed in disposable adding, add 3,5-dinitrobenzoic acid 0.424 gram (2mmol) and HOBt (1-hydroxy benzo triazole) 0.298 gram (2.2mmol), after reaction mixture is cooled to 0 ℃, drip the dichloromethane solution 5mL of DCC 0.46 gram (2.2mmol), being warming up to room temperature reaction behind the continuation low-temp reaction 0.5h after dropwising spends the night, after TLC shows that reaction finishes, suction filtration is removed a large amount of white precipitate shape by product DCU of generation, organic phase is with water, saturated sodium bicarbonate aqueous solution, saturated sodium-chloride water solution washing back anhydrous sodium sulfate drying, revolve and obtain oily matter after desolvating, the silicagel column column chromatography, eluent is (with acetoacetic ester: obtain faint yellow solid sherwood oil=1: 3), productive rate 62%.m.p：129-131℃；IR(KBr，cm -1)：v?3491，3260，3114，2958，2874，1752，1664，1645，1541，1343，1215； 1HNMR(400MHz，CDCl 3)：δ9.14(m，1H，Ar-H)，8.90(m，2H，Ar-H)，4.83(m，1H，CHCOOCH 3)，3.84(s，3H，OCH 3)，2.36(m，1H，CH(CH 3) 2)，1.04(d，6H，J＝3.6Hz，CH(CH 3) 2)； 13CNMR(100MHz，CDCl 3)：δ172.66，162.67，148.69，137.28，127.26，121.32，58.19，52.73，31.53，19.04，18.03。
Figure G2008101675579D0000081
Formula I
2) mark of precursor 18F mark (formula J) and hydrolysis (formula K)
18F -After being caught by anion column QMA, with containing 10mg K2.2.2 and 3mg K 2CO 3The 1mL acetonitrile and the mixed solution of 0.5mL water it is flushed in the reaction flask, the anhydrous acetonitrile that in reaction flask, adds 0.5mL, be heated to 100 ℃, constantly feed nitrogen, utilize acetonitrile and water azeotropic water removing, after treating solvent dried up, the anhydrous acetonitrile that adds 0.5mL more respectively, repeat twice of this operation, 5mg2-(3, the 5-dinitrobenzene) benzoylamino-3 Methylbutanoic acid methyl esters is dissolved in anhydrous N, and dinethylformamide solution is poured in the reaction flask, be warming up to 125 ℃ rapidly, keep about this thermotonus 30min, stopped reaction adds about 10mL water reaction system is diluted, by Sep-Pak C18 post, filtrate collection (is not mainly participated in reacting in headpin again 18F -), and then with 10mL water washing pillar, will (guarantee and will not participate in reaction in filtrate collection to 2 bottle 18F -Thoroughly drip washing is clean), with nitrogen Sep-Pak C18 post is dried up, with 2mL acetonitrile washing C18 post, in filtrate collection to 3 bottle, obtain intermediate product 2-(3-fluorine 18-5-dinitrobenzene) benzoylamino-3 Methylbutanoic acid methyl esters (3a), through HPLC (band radioactivity probe) separation and purification (HPLC condition: flow velocity 1mL/min, moving phase is acetonitrile: water=70%: 30%, retention time is 7.9min), after with nitrogen the acetonitrile in the solution being dried up, in the mixing solutions of water and methyl alcohol,, use the hcl acidifying of a certain amount of 1mol/L again, obtain with a certain amount of lithium hydroxide hydrolysis 18F marked product 2-(3-fluorine 18-5-dinitrobenzene) benzoylamino-3 Methylbutanoic acid (4a), entire reaction course needs 60-80min.Measure (HPLC condition: flow velocity 1mL/min, moving phase is acetonitrile: water=70%: 30%, retention time are 3.0min) through HPLC (band radioactivity probe), hydrolysis reaction is very complete, and radiochemical purity reaches the bio distribution requirement of experiment.
Formula J
Figure G2008101675579D0000091
Formula K
Lipid is an important physical and chemical parameter of bioactive compounds, and it is as follows that 2-(3-fluorine 18-5-dinitrobenzene) benzoylamino-3 Methylbutanoic acid lipid is measured enforcement:
In centrifuge tube, add 2mL n-Octanol and 1.9mL pH successively and be 7.4 phosphate buffer soln, and radioactive activity is about the 0.1mL aqueous solution of 2-(3-fluorine 18-5-dinitrobenzene) benzoylamino-3 Methylbutanoic acid of 8-10 μ Ci, the centrifugal layering 5min in back fully vibrates, get each 0.1mL of organic phase and water respectively in clean tube, measure its radiocounting N respectively, calculation of distribution coefficient P=N Have/ N Water, repeat to average after this operation 3 times, P is taken the logarithm, logP is this 18The lipid of F marked product.
The lipid that records 2-(3-fluorine 18-5-dinitrobenzene) benzoylamino-3 Methylbutanoic acid as stated above is-0.53.
Abnormal toxicity test:
Undertaken by Pharmacopoeia of People's Republic of China described method of version in 2005.10 normal kunming mices (18-20g) tail vein is injected 0.5mL (37MBq) 2-(3-fluorine 18-5-dinitrobenzene) benzoylamino-3 Methylbutanoic acid injection liquid (being equivalent to hundreds of times to adult's consumption), observed 48 hours.The mouse growth is normal, and no death and untoward reaction phenomenon take place.Dissect the back and observe, do not see any organ damage.The undue toxicity inspection meets requirements of radiopharmaceuticals..

Claims (7)

  1. One kind novel 18F mark m-nitro benzoyl amino acids compounds is characterized in that: an end has 3-fluorine 18-5-oil of mirbane formyl structure; The other end has the a-amino acid structure, has substituent R to be positioned on the alpha site of carboxyl group, is hydrogen, methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, benzyl, 2-methylmercaptoethyl, propyloic, carboxylic propyl group, phenyl, imidazoles methyl.Two-end structure directly links to each other by amido linkage.Structure is suc as formula A.
    Figure F2008101675579C0000011
    Formula A
  2. 2. claim 1 is described 18F mark m-nitro benzoyl amino acids compounds, it is characterized in that: an end has 3,5-dinitrobenzene formyl structure; The other end has a-amino acid methyl esters structure, and substituent R is positioned on the ester group α position, is hydrogen, methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, benzyl, 2-methylmercaptoethyl, propyloic, carboxylic propyl group, phenyl, imidazoles methyl.Two-end structure directly links to each other by amido linkage.Structure is suc as formula B:
    Formula B
  3. 3. the described series of claim 1 18F mark m-nitro benzoyl amino acids compounds may further comprise the steps;
    18F -After being caught by anion column QMA, with containing 10mg K2.2.2 and 3mg K 2CO 3The 1mL acetonitrile and the mixed solution of 0.5mL water it is flushed in the reaction flask, the anhydrous acetonitrile that in reaction flask, adds 0.5mL, be heated to 100 ℃, constantly feed nitrogen, utilize acetonitrile and water azeotropic water removing, after treating solvent dried up, add the anhydrous acetonitrile of 0.5mL more respectively, repeat twice of this operation, precursor compound shown in the 5mg formula B is dissolved in anhydrous N, dinethylformamide solution is poured in the reaction flask, is warming up to 125 ℃ rapidly, keeps this thermotonus about 30 minutes, stopped reaction, add about 10mL water reaction system is diluted, by Sep-Pak C18 post, filtrate collection (is not mainly participated in reacting in headpin again 18F -), and then with 10mL water washing pillar, will (guarantee and will not participate in reaction in filtrate collection to 2 bottle 18F -Thoroughly drip washing is clean), with nitrogen Sep-Pak C18 post is dried up, with 2mL acetonitrile washing C18 post, in filtrate collection to 3 bottle, obtain 18F mark intermediate product.
    18F mark intermediate product is through HPLC (band radioactivity probe) separation and purification, after with nitrogen the acetonitrile in the solution being dried up, with a certain amount of lithium hydroxide hydrolysis, uses the hcl acidifying of a certain amount of 1mol/L again in the mixing solutions of water and methyl alcohol, obtains 18F is for end product, and this process needs 30 minutes approximately.
  4. 4. claim 3 is described 18The F marking method is characterized in that: 18F -Obtaining of source is with containing 10mg K2.2.2 and 3mg K 2CO 31mL acetonitrile and the flushing of the mixed solution of 0.5mL water medical 18F -The QMA anion column obtains, and with second eyeball azeotropic water removing.
  5. 5. claim 3 is described 18The F marking method is characterized in that: use DMF as reaction solvent, K2.2.2 is a phase-transfer catalyst.
  6. 6. claim 3 is described 18The F marking method is characterized in that: the labeled reactant optimum temps is 120-125 ℃, and Best Times is 30 minutes.
  7. 7. claim 1 is described 18F mark m-nitro benzoyl amino acids compounds is as the application of positron emission tomography (PET) tumor developer.
CN200810167557.9A 2008-10-10 2008-10-10 Novel 18F labeled m-nitro benzoyl amino acids, preparation method and application thereof in tumor imaging Expired - Fee Related CN101723848B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN200810167557.9A CN101723848B (en) 2008-10-10 2008-10-10 Novel 18F labeled m-nitro benzoyl amino acids, preparation method and application thereof in tumor imaging

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN200810167557.9A CN101723848B (en) 2008-10-10 2008-10-10 Novel 18F labeled m-nitro benzoyl amino acids, preparation method and application thereof in tumor imaging

Publications (2)

Publication Number Publication Date
CN101723848A true CN101723848A (en) 2010-06-09
CN101723848B CN101723848B (en) 2014-04-16

Family

ID=42445481

Family Applications (1)

Application Number Title Priority Date Filing Date
CN200810167557.9A Expired - Fee Related CN101723848B (en) 2008-10-10 2008-10-10 Novel 18F labeled m-nitro benzoyl amino acids, preparation method and application thereof in tumor imaging

Country Status (1)

Country Link
CN (1) CN101723848B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101862463A (en) * 2010-06-17 2010-10-20 复旦大学 Preparation method of 18F-labeled nano particle and application thereof
WO2014045306A2 (en) 2012-09-21 2014-03-27 Kasina Laila Innova Pharmaceuticals Private Limited F-18 radiolabeled compounds for diagnosing and monitoring kidney function

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1172721C (en) * 2002-11-20 2004-10-27 南方医院 Tumour positive electron developer S-(18 fluro-n-alkyl)-L-methionine and its preparation method

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101862463A (en) * 2010-06-17 2010-10-20 复旦大学 Preparation method of 18F-labeled nano particle and application thereof
WO2014045306A2 (en) 2012-09-21 2014-03-27 Kasina Laila Innova Pharmaceuticals Private Limited F-18 radiolabeled compounds for diagnosing and monitoring kidney function
JP2015535824A (en) * 2012-09-21 2015-12-17 カシナ ライラ イノバ ファーマシューティカルズ プライベート リミテッド F-18 radiolabeled compound for diagnosing and monitoring renal function
EP2900629A4 (en) * 2012-09-21 2016-05-18 Kasina Laila Innova Pharmaceuticals Private Ltd F-18 radiolabeled compounds for diagnosing and monitoring kidney function
AU2013319747B2 (en) * 2012-09-21 2018-02-08 Kasina Laila Innova Pharmaceuticals Private Limited F-18 radiolabeled compounds for diagnosing and monitoring kidney function

Also Published As

Publication number Publication date
CN101723848B (en) 2014-04-16

Similar Documents

Publication Publication Date Title
EA017713B1 (en) [f-18]-labeled l-glutamic acid, [f-18]-labeled l-glutamine, derivatives thereof and use thereof and processes for their preparation
CN107353323B (en) Al18F-labeled PSMA (PSMA) targeted inhibitor and preparation method and application thereof
KR20110038725A (en) Psma-binding agents and uses thereof
CN113372285B (en) Prostate specific membrane antigen inhibitor, radionuclide marker, preparation method and application thereof
CN101723849B (en) Novel 18F labeled amino acid derivatives, preparation method and application thereof in tumor imaging
JPWO2009078396A1 (en) Method for producing radioactive fluorine-labeled organic compound
CN101723846B (en) Novel 18F labeled p-nitro benzoyl amino acid derivatives, preparation method and application thereof in tumor imaging
CN103254139B (en) Novel 18f marks 4-amino quinazoline derivative and preparation method thereof and applies with PET tumor imaging
Heinrich et al. Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent
CN101723850B (en) Novel 18F labeled aromatic amino acids, preparation method and application thereof in tumor imaging
CN101723848B (en) Novel 18F labeled m-nitro benzoyl amino acids, preparation method and application thereof in tumor imaging
CN104830316A (en) Targeted probe for nuclide labeling and preparation method and application of targeted probe
CN101768208B (en) Novel 18F-labelled polypeptide, preparation method and application thereof in tumor imaging
KR20120089846A (en) Single diastereomers of 4-fluoroglutamine and methods for their preparation and use
CN101723847B (en) Novel 18F labeled p-nitro benzoyl amino acid compound and preparation method and application thereof
RU2395489C2 (en) [f-18] labelled l-glutamic acid, [f-18] labelled l-glutamine, derivatives thereof and use thereof, as well as synthesis method thereof
EP3216796B1 (en) Phosphonium compound and production method therefor
JP2690018B2 (en) Radioactive diagnostic agent consisting of glucosamine derivative
CN113387927A (en) Nitroimidazole derivative for preparing hypoxia imaging agent and preparation method and application thereof
KR101389258B1 (en) Nitroimidazole-amino acid compound type nuclide hypoxia imaging agent and intermediates for preparing them
Liu et al. Design, synthesis and evaluation of a novel glutamine derivative (2 S, 4 R)-2-amino-4-cyano-4-[18 F] fluorobutanoic acid
CN113501789B (en) Nitroimidazole derivative and preparation method and application thereof
CN109438265B (en) Compound with affinity with brown adipose tissue and preparation method and application thereof
CN106631863B (en) The radiation synthetic method of sub- glutamic acid-type PET developers
CN115368342B (en) Fibroblast active protein inhibitor, radionuclide marker, preparation method and application thereof

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
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20140416

Termination date: 20141010

EXPY Termination of patent right or utility model