CN105884868B - It is a kind of18The affinity body class compound and the preparation method and application thereof of F label - Google Patents
It is a kind of18The affinity body class compound and the preparation method and application thereof of F label Download PDFInfo
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Abstract
The invention belongs to radiopharmaceutical and the field of nuclear medicines, and in particular to a kind of18The affinity body class compound and the preparation method and application thereof of F label.It is of the present invention18The affinity body class compound of F label, on the one hand, tumour is higher to its uptake values, and tumor imaging sensitivity is higher, and on the other hand, liver is lower to its uptake values, smaller to the toxic side effect of liver；Animal experiments show that described18The affinity body class compound of F label, residence time, higher target/non-target ratio and the preferable pharmacokinetic property that tumour is higher to its uptake values, shorter, biological property is excellent, can be used as the PET tumor imaging agent for targeting HER2 receptor；Not only cost is relatively low for preparation method, simple and convenient for operation, but also mark rate is higher, the radiochemical purity of marked product is higher, is conducive to be prepared18The affinity body class compound of F label is clinically promoted and applied as the PET tumor imaging agent for targeting HER2 receptor.
Description
Technical field
The invention belongs to radiopharmaceutical and the field of nuclear medicines, and in particular to a kind of18F label affinity body class compound and
Preparation method and application.
Background technique
Sophisticated technology of the positron emission computerized tomography (PET) as 21 century biomedical research and clinical diagnosis, quilt
Referred to as " imaging of living body biochemistry " technology, can be from external noninvasive, quantitative, the dynamically intracorporal physiology of observer, Biochemical changes, hole
Examine the activity of labeled drug in normal person or in patient body.Compared with SPECT, PET has high resolution and can quantitative analysis etc.
Clear superiority.
18F has close to 100% positive electron efficiency, low positive electron energy (0.64 million electro-volt) and relatively short object
Manage half-life period (t1/2=109.7min) the features such as, it is ideal PET imaging nucleic.
Polypeptide has the advantages that tissue infiltration is quickly removed rapidly, in blood, immunogenicity is low etc., is to prepare18F label imaging
The suitable carrier of agent.ErbB-2 (human epithelial growth factor receptor-2,
HER2 it) is incorporated in the transmembrane receptor sample albumen of cell membrane surface, there is tyrosine kinase activity, it is logical by activation downstream signal
Growth, activation and the breeding of road participation cell.HER2 express in the normal tissue it is not significant, but in breast cancer, oophoroma,
It is highly expressed in the malignant tumours such as cervical carcinoma and lung cancer.Therefore, HER2 is the important target spot of tumor diagnosis and therapy.Affine body
It (Affibody) also known as " artificial antibody ", is a kind of novel polypeptide based on nonimmune albumen affinity ligand.Affinity body ZHER2:
342 are made of 58 amino acid residues, have the binding ability of specificity with HER2,18F marked product is suitable for tumor imaging,
It can be used for the early diagnosis and curative effect monitoring of tumour.
Currently, being carried out to affinity body18The method of F label, comprising the following steps: QMA column purification18F, prepared by multistep reaction
Prothetic group (18F-SFB or18F-FBEM) and its purify, couple peptide, HPLC purifying etc.；This method not only time-consuming (about 1~2h), behaviour
Make it is more complex, and in product18The general reference numeral rate of F is lower.18F ion is easily combined with metal (such as: aluminium), generation18F- aluminium
Complex (18F- Al) can by NOTA chela and.Using the principle, McBride etc. passes through18The peptide of F-Al and connection NOTA carry out straight
It is reversed to answer, it is made18F marks peptide.The preparation method, without the preparation and purification etc. of prothetic group, preparation time shortens, and marker has
There is high specific activity.
Kramer-Marek G etc. is prepared for18F-FBEM- (ZHER2:342), can be used as and target HER2 receptor
Tumour imaging agent (Kramer-Marek G et al, Eur J Nucl Med Mol Imaging, 2008,35,1008-
1018).However, on the one hand, tumour is to above-mentioned18The uptake values of F-FBEM- (ZHER2:342) are lower, this causes tumor imaging clever
Sensitivity is lower；On the other hand, liver is to above-mentioned18The uptake values of F-FBEM- (ZHER2:342) are higher, this leads to the poison to liver
Side effect is larger；In addition, above-mentioned18The preparation method of F-FBEM- (ZHER2:342) is more complex, to limit to a certain extent
Its clinical application.
Therefore, research tumor imaging sensitivity is higher, smaller to the toxic side effect of liver, preparation method is easier18F mark
The PET tumor imaging agent for targeting HER2 receptor of note is of great significance.
Summary of the invention
For this purpose, the present invention proposes one kind18The affinity body class compound of F label, and preparation method and application are provided in turn.
In order to solve the above technical problems, the present invention is achieved through the following technical solutions:
The present invention provides formula (I) compound represented,
Val-Asp-Asn-Lys-Phe-Asn-Lys-Glu-Met-Arg-Asn-Ala-Tyr-Trp-Glu-Ile-Ala-
Leu-Leu-Pro-Asn-Leu-Asn-Asn-Gln-Gln-Lys-Arg-Ala-Phe-Ile-Arg-Ser-Leu-Tyr- Asp-
Asp-Pro-Ser-Gln-Ser-Ala-Asn-Leu-Leu-Ala-Glu-Ala-Lys-Lys-Leu-Asn-Asp- Ala-Gln-
Ala-Pro-Lys-Asn-Asp-Arg-Gly-Gly-Gly-R1
(Ⅰ)
Wherein, R1Expression be
The present invention also provides the medicine boxs that one kind is used to prepare formula (I) compound represented, and the reagent of the medicine box includes: 1
~10 molar part formula (II) compounds represented and 1 molar part formula alchlor,
Val-Asp-Asn-Lys-Phe-Asn-Lys-Glu-Met-Arg-Asn-Ala-Tyr-Trp-Glu-Ile-Ala-
Leu-Leu-Pro-Asn-Leu-Asn-Asn-Gln-Gln-Lys-Arg-Ala-Phe-Ile-Arg-Ser-Leu-Tyr- Asp-
Asp-Pro-Ser-Gln-Ser-Ala-Asn-Leu-Leu-Ala-Glu-Ala-Lys-Lys-Leu-Asn-Asp- Ala-Gln-
Ala-Pro-Lys-Asn-Asp-Arg-Gly-Gly-Gly-R2
(Ⅱ)
Wherein, R2Expression be
Preferably, in the above-mentioned medicine box for being used to prepare formula (I) compound represented of the present invention, the reagent packet of the medicine box
It includes: 1~5 molar part formula (II) compound represented and 1 molar part alchlor.
It is further preferred that in the above-mentioned medicine box for being used to prepare formula (I) compound represented of the present invention, the examination of the medicine box
Agent includes: 3 molar part formula (II) compounds represented and 1 molar part alchlor.
It is further preferred that in the above-mentioned medicine box for being used to prepare formula (I) compound represented of the present invention, the examination of the medicine box
Agent further include: Acetic acid-sodium acetate buffer.
It is further preferred that in the above-mentioned medicine box for being used to prepare formula (I) compound represented of the present invention, the acetic acid-vinegar
Sour sodium buffer is 0.4~0.6mol/L, and pH is 3.0~5.0.
It is further preferred that in the above-mentioned medicine box for being used to prepare formula (I) compound represented of the present invention, the acetic acid-vinegar
Sour sodium buffer is 0.5mol/L, pH 4.0.
It is further preferred that in the above-mentioned medicine box for being used to prepare formula (I) compound represented of the present invention, shown in formula (II)
Compound and the alchlor are freeze-dried powder.
The present invention also provides a kind of preparation methods of above-mentioned medicine box, comprising the following steps:
(1) formula (II) compound represented of selected molar part is dissolved in the Acetic acid-sodium acetate buffer, obtains solution
A, it is spare；
(2) aluminium chloride of selected molar part is dissolved in the Acetic acid-sodium acetate buffer, obtains solution B, it is spare；
(3) solution A and the solution B are uniformly mixed, obtain solution C, it is spare；
(4) solution C is sterile filtered, is sub-packed in container, freeze-drying to get.
It is further preferred that the container is control antibiotic bottle in the above-mentioned preparation method of the present invention.
The present invention also provides the medicine boxs that above-mentioned preparation method is prepared.
The present invention also provides application of the above-mentioned medicine box in preparation formula (I) compound represented.
The present invention also provides a kind of preparation methods of formula (I) compound represented, comprising the following steps:
(a) acetic acid solution is added into above-mentioned medicine box, is dissolved, acetonitrile is then added and matched18F aqueous solution, 80
5~20min of confined reaction at~110 DEG C, it is cooling, obtain reaction solution；
(b) water dilution is added in the reaction solution, injection Sep-Pak C18 separates pillar, described in PBS and water flushing
Sep-Pak C18 separates pillar, obtains marked product；
(c) with marked product described in ethanol elution, with normal saline dilution, be sterile filtered to get.
Preferably, the preparation method of above-mentioned formula (I) compound represented of the present invention, comprising the following steps:
(a) acetic acid solution that 10~50 μ L mass fractions are 2~8% is added into above-mentioned medicine box, dissolves, is then added
100~400 μ L acetonitriles and 100~200 μ L are the 20~150mCi matched18F aqueous solution, at 80~110 DEG C confined reaction 5~
20min, it is cooling, obtain reaction solution；
(b) water dilution is added in the reaction solution, injection Sep-Pak C18 separates pillar, described in PBS and water flushing
Sep-Pak C18 separates pillar, obtains marked product；
(c) marked product described in 0.2~1mL ethanol elution, with normal saline dilution, be sterile filtered to get.
It is further preferred that the preparation method of above-mentioned formula (I) compound represented of the present invention, comprising the following steps:
(a) acetic acid solution that 20 μ L mass fractions are 5% is added into above-mentioned medicine box, dissolves, 200 μ L second is then added
Nitrile and 150 μ L are the 50mCi matched18F aqueous solution, the confined reaction 10min at 100 DEG C is cooling, obtains reaction solution；
(b) water dilution is added in the reaction solution, injection Sep-Pak C18 separates pillar, described in PBS and water flushing
Sep-Pak C18 separates pillar, obtains marked product；
(c) with marked product described in 0.5mL ethanol elution, with normal saline dilution, be sterile filtered to get.
The present invention also provides formula (I) compounds represented or above-mentioned medicine box to prepare the application in PET imaging agent.
Compared with prior art, above-mentioned technical proposal of the invention has the advantage that
(1) of the present invention18The affinity body class compound of F label, on the one hand, tumour is higher to its uptake values, and tumour is aobvious
Picture sensitivity is higher, and on the other hand, liver is lower to its uptake values, smaller to the toxic side effect of liver；Animal experiments show that institute
It states18The affinity body class compound of F label, tumour is higher to its uptake values, shorter residence time, higher target/non-target ratio
With preferable pharmacokinetic property, biological property is excellent, can be used as the PET tumor imaging agent for targeting HER2 receptor；
(2) present invention can be prepared described by the way that medicine box is made in reaction raw materials and reagent by easy operation18F mark
The affinity body class compound of note, not only cost is relatively low for the preparation method, simple and convenient for operation, but also mark rate is higher, label produces
The radiochemical purity of object is higher, is conducive to be prepared described18The affinity body class compound of F label, which is used as, targets HER2
The PET tumor imaging agent of receptor clinically promotes and applies.
Detailed description of the invention
In order to make the content of the present invention more clearly understood, it below according to specific embodiments of the present invention and combines
Attached drawing, the present invention is described in further detail, in which:
Fig. 1 is injection 3.7 MBq (100 μ Ci)18F-FAl-NOTA-MAL-M59 ZHER2:34230min、60min、
After 120min and 240 min, the coronal microPET imaging figure of SKOV-3 Transplanted tumor model mouse whole body decay correction, knub position is such as
Shown in arrow；
Fig. 2 is injection 3.7 MBq (100 μ Ci)18F-FAl-NOTA-MAL-M59 ZHER2:34230min、60min、
After 120min and 240 min, in SKOV-3 Transplanted tumor model mouse body, tumour, liver, kidney and muscle pair18F-FAl-NOTA-
MAL-M59The quantitative uptake values of ZHER2:342, ROIs are indicated with average %ID/g ± SD.
Specific embodiment
Technical solution of the present invention is clearly and completely described below in conjunction with attached drawing, it is clear that described implementation
Example is a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, ordinary skill
Personnel's every other embodiment obtained without making creative work, shall fall within the protection scope of the present invention.
In following embodiment of the present invention and experimental example, formula (I) compound represented,
Val-Asp-Asn-Lys-Phe-Asn-Lys-Glu-Met-Arg-Asn-Ala-Tyr-Trp-Glu-Ile-Ala-
Leu-Leu-Pro-Asn-Leu-Asn-Asn-Gln-Gln-Lys-Arg-Ala-Phe-Ile-Arg-Ser-Leu-Tyr- Asp-
Asp-Pro-Ser-Gln-Ser-Ala-Asn-Leu-Leu-Ala-Glu-Ala-Lys-Lys-Leu-Asn-Asp- Ala-Gln-
Ala-Pro-Lys-Asn-Asp-Arg-Gly-Gly-Gly-R1
(Ⅰ)
Wherein, R1Expression be
Formula (II) compound represented can synthesize (Mol Imaging Biol. 2014,16 by the method for the prior art
(4), 578-85),
Val-Asp-Asn-Lys-Phe-Asn-Lys-Glu-Met-Arg-Asn-Ala-Tyr-Trp-Glu-Ile-Ala-
Leu-Leu-Pro-Asn-Leu-Asn-Asn-Gln-Gln-Lys-Arg-Ala-Phe-Ile-Arg-Ser-Leu-Tyr- Asp-
Asp-Pro-Ser-Gln-Ser-Ala-Asn-Leu-Leu-Ala-Glu-Ala-Lys-Lys-Leu-Asn-Asp- Ala-Gln-
Ala-Pro-Lys-Asn-Asp-Arg-Gly-Gly-Gly-R2
(Ⅱ)
Wherein, R2Expression be
The specific structure sequence of affinity body ZHER2:342 is referring to following document: Structural basis for high-
affinity HER2receptor binding by an engineered protein.Proceedings of the
National Academy of Sciences of the United States of America, 2010,107 (34),
15039–15044。
Remaining reagent and solvent are commercially available product, and the concentration of specific reagent can be configured according to the method for the prior art.
Embodiment 1
The present embodiment is used to prepare in the medicine box of formula (I) compound represented, and reagent includes: 25nmol formula (II) institute
The compound shown, 12nmol alchlor, the Acetic acid-sodium acetate buffer that 0.5mol/L, pH are 4.0；
The preparation method of the medicine box, comprising the following steps:
(1) selected mole formula (II) compound represented the Acetic acid-sodium acetate that 0.5mol/L, pH are 4.0 is dissolved in delay
In fliud flushing, solution A is obtained, it is spare；
(2) selected mole of aluminium chloride is dissolved in the Acetic acid-sodium acetate buffer that 0.5mol/L, pH are 4.0, obtains solution
B, it is spare；
(3) solution A and the solution B are uniformly mixed, obtain solution C, it is spare；
(4) solution C is sterile filtered, is sub-packed in control antibiotic bottle, be freeze-dried 24 hours, jump a queue
Sealing to get.
The preparation method of the present embodiment formula (I) compound represented, comprising the following steps:
(a) acetic acid solution that 20 μ L mass fractions are 5% is added into above-mentioned medicine box, dissolves, 200 μ L second is then added
Nitrile and 150 μ L are the 50mCi matched18F aqueous solution, the confined reaction 10min at 100 DEG C is cooling, obtains reaction solution；
(b) water dilution is added in the reaction solution, injection Sep-Pak C18 separates pillar, described in PBS and water flushing
Sep-Pak C18 separates pillar, obtains marked product；
(c) with marked product described in 0.5mL ethanol elution, with normal saline dilution, be sterile filtered to get.
Embodiment 2
The present embodiment is used to prepare in the medicine box of formula (I) compound represented, and reagent includes: shown in 1nmol formula (II)
Compound, 1nmol alchlor, 0.4mol/L, pH be 5.0 acetic acid-sodium-acetate buffer；
The preparation method of the medicine box, comprising the following steps:
(1) selected mole formula (II) compound represented the Acetic acid-sodium acetate that 0.4mol/L, pH are 5.0 is dissolved in delay
In fliud flushing, solution A is obtained, it is spare；
(2) selected mole of aluminium chloride is dissolved in the Acetic acid-sodium acetate buffer that 0.4mol/L, pH are 5.0, obtains solution
B, it is spare；
(3) solution A and the solution B are uniformly mixed, obtain solution C, it is spare；
(4) solution C is sterile filtered, is sub-packed in control antibiotic bottle, be freeze-dried 24 hours, jump a queue
Sealing to get.
The preparation method of the present embodiment formula (I) compound represented, comprising the following steps:
(a) acetic acid solution that 10 μ L mass fractions are 8% is added into above-mentioned medicine box, dissolves, 100 μ L second is then added
Nitrile and 200 μ L are the 20mCi matched18F aqueous solution, the confined reaction 5min at 110 DEG C is cooling, obtains reaction solution；
(b) water dilution is added in the reaction solution, injection Sep-Pak C18 separates pillar, described in PBS and water flushing
Sep-Pak C18 separates pillar, obtains marked product；
(c) with marked product described in 1mL ethanol elution, with normal saline dilution, be sterile filtered to get.
Embodiment 3
The present embodiment is used to prepare in the medicine box of formula (I) compound represented, and reagent includes: shown in 5nmol formula (II)
Compound, 1nmol alchlor, 0.6mol/L, pH be 3.0 acetic acid-sodium-acetate buffer；
The preparation method of the medicine box, comprising the following steps:
(1) selected mole formula (II) compound represented the Acetic acid-sodium acetate that 0.6mol/L, pH are 3.0 is dissolved in delay
In fliud flushing, solution A is obtained, it is spare；
(2) selected mole of aluminium chloride is dissolved in the Acetic acid-sodium acetate buffer that 0.6mol/L, pH are 3.0, obtains solution
B, it is spare；
(3) solution A and the solution B are uniformly mixed, obtain solution C, it is spare；
(4) solution C is sterile filtered, is sub-packed in control antibiotic bottle, be freeze-dried 24 hours, jump a queue
Sealing to get.
The preparation method of the present embodiment formula (I) compound represented, comprising the following steps:
(a) acetic acid solution that 50 μ L mass fractions are 2% is added into above-mentioned medicine box, dissolves, 400 μ L second is then added
Nitrile and 100 μ L are the 150mCi matched18F aqueous solution, the confined reaction 20min at 80 DEG C is cooling, obtains reaction solution；
(b) water dilution is added in the reaction solution, injection Sep-Pak C18 separates pillar, described in PBS and water flushing
Sep-Pak C18 separates pillar, obtains marked product；
(c) with marked product described in 0.2mL ethanol elution, with normal saline dilution, be sterile filtered to get.
Embodiment 4
The difference that the present embodiment is used to prepare the medicine box and the medicine box of embodiment 1 of formula (I) compound represented is only that: formula
(II) compound represented is 6nmol, remaining reagent is same as Example 1；
The preparation method of the present embodiment medicine box and the difference of the preparation method of the medicine box of embodiment 1 be only that, formula (II) institute
The compound shown is 6nmol, remaining operating procedure is identical as the preparation method of the medicine box of embodiment 1.
The preparation method of the present embodiment formula (I) compound represented and the preparation side of 1 formula of embodiment (I) compound represented
Method is identical.
Embodiment 5
The difference that the present embodiment is used to prepare the medicine box and the medicine box of embodiment 1 of formula (I) compound represented is only that: formula
(II) compound represented is 9nmol, remaining reagent is same as Example 1；
The preparation method of the present embodiment medicine box and the difference of the preparation method of the medicine box of embodiment 1 be only that, formula (II) institute
The compound shown is 9nmol, remaining operating procedure is identical as the preparation method of the medicine box of embodiment 1.
The preparation method of the present embodiment formula (I) compound represented and the preparation side of 1 formula of embodiment (I) compound represented
Method is identical.
Experimental example 1The identification experiment of formula (I) compound represented
1, experiment purpose
The retention time and radiochemical purity of detection formula (I) compound represented.
2, experimental method
2.1 laboratory apparatus and reagent
Waters 515 is pumped, UV detector, gamma-ray detector.
Chromatographic column: Phenomenex Luna C-18 (4.6 × 250mm) analytical column.
Mobile phase: mobile phase A is the acetonitrile solution containing 0.1% trifluoroacetic acid, and Mobile phase B is containing 0.1% trifluoroacetic acid
Aqueous solution.
2.2 experimental method
Following procedure carries out gradient elution: 0-2min, A:B 5%:95%；2-32min, A:B be 5%:95% →
65%:35%；Flow velocity 1.0mL/min, Detection wavelength 218nm.
Each 20 μ L of PBS solution of formula (I) compound represented of Example 1-5 preparation respectively, injects liquid chromatograph,
Measurement.
3, experimental result
By testing it is found that the retention time of formula (I) compound represented is about 13min, radiochemical purity is all larger than
95%.
Experimental example 2The vitro stability of formula (I) compound represented is tested
1, experiment purpose
The radiochemical purity of formula (I) compound represented after different time is placed in detection.
2, experimental method
At room temperature, the PBS solution of formula (I) compound represented respectively prepared embodiment 1-5 places different time
(0.5h, 1h and 2h) carries out HPLC analysis according to the experimental method of experimental example 1, calculates radiochemical purity.
3, experimental result
By experiment it is found that formula (I) compound represented can be stabilized 4h or more at room temperature, appearance and activation
Purity is learned without significant change.
Experimental example 3The MicroPET of formula (I) compound represented images experiment
1, experiment purpose
It is acted on by zoopery verifying and the MicroPET imaging of analysis mode (I) compound represented.
2, experimental method
Under isoflurane anesthesia, lotus human ovarian cancer SKOV-3 tumour nude mice tail vein injection about 3.7MBq (100 μ Ci) is real
Apply formula (I) compound represented of the preparation of example 1.
Image reconstruction is carried out using sequential 2 D subset expectation maximization (two-dimentional OSEM) algorithm.Each MicroPET is swept
When retouching, region of interest (ROI) is delineated using the software that supplier provides on whole body decay correction coronal image.From multiple ROI
Tumour, liver, kidney and radioactive activity (accumulative) in muscle are obtained in average pixel value and are converted into MBq/mL, resulting value
%ID/g (it is assumed that tissue density is 1g/mL) is obtained divided by injection dosage.
3, experimental result
Experimental result is as depicted in figs. 1 and 2.
By Fig. 1 and Fig. 2 it is found that after injection 60min, tumour to the uptake values of formula (I) compound represented be 16.54 ±
2.69%ID/g, be all remarkably higher than document (Kramer-Marek G et al, Eur J Nucl Med Mol Imaging,
2008,35,1008-1018) tumour pair reported189.73 ± 1.91%ID/g of uptake values of F-FBEM- (ZHER2:342).
By Fig. 1 and Fig. 2 it is found that after injection 30min, in addition to tumour, formula (I) compound represented height in kidney is dense
It is poly-, then quickly exclude.
By Fig. 1 and Fig. 2 it is found that uptake values of formula (I) compound represented in liver are 3.02 ± 0.51%ID/g,
Substantially less than document (Kramer-Marek G et al, Eur J Nucl Med Mol Imaging, 2008,35,1008-
1018) liver pair reported185.04 ± 0.69%ID/g of uptake values of F-FBEM- (ZHER2:342).
To sum up, of the present invention18The affinity body class compound of F label, on the one hand, tumour is higher to its uptake values, tumour
It is higher to image sensitivity, on the other hand, liver is lower to its uptake values, smaller to the toxic side effect of liver；Animal experiments show that
It is described18The affinity body class compound of F label, tumour is higher to its uptake values, shorter residence time, higher target/non-target ratio
Value and preferable pharmacokinetic property, biological property is excellent, can be used as the PET tumor imaging agent for targeting HER2 receptor；
The present invention can be prepared described by the way that medicine box is made in reaction raw materials and reagent by easy operation18The affinity body class of F label
Compound, not only cost is relatively low for the preparation method, simple and convenient for operation, but also mark rate is higher, the radiochemistry of marked product
Purity is higher, is conducive to be prepared described18The affinity body class compound of F label is as the tumour for targeting HER2 receptor
PET imaging agent clinically promotes and applies.
Obviously, the above embodiments are merely examples for clarifying the description, and does not limit the embodiments.It is right
For those of ordinary skill in the art, can also make on the basis of the above description it is other it is various forms of variation or
It changes.There is no necessity and possibility to exhaust all the enbodiments.And it is extended from this it is obvious variation or
It changes still within the protection scope of the invention.
Claims (10)
- Formula 1. (I) compound represented:Val-Asp-Asn-Lys-Phe-Asn-Lys-Glu-Met-Arg-Asn-Ala-Tyr-Trp-Glu-Ile-Ala-Leu- Leu-Pro-Asn-Leu-Asn-Asn-Gln-Gln-Lys-Arg-Ala-Phe-Ile-Arg-Ser-Leu-Tyr-Asp-Asp- Pro-Ser-Gln-Ser-Ala-Asn-Leu-Leu-Ala-Glu-Ala-Lys-Lys-Leu-Asn-Asp-Ala-Gln-Ala- Pro-Lys-Asn-Asp-Arg-Gly-Gly-Gly-R1(Ⅰ)Wherein, R1Expression be
- 2. the medicine box that one kind is used to prepare formula (I) compound represented, which is characterized in that the reagent of the medicine box includes: 1~10 Molar part formula (II) compound represented and 1 molar part alchlor,Val-Asp-Asn-Lys-Phe-Asn-Lys-Glu-Met-Arg-Asn-Ala-Tyr-Trp-Glu-Ile-Ala-Leu- Leu-Pro-Asn-Leu-Asn-Asn-Gln-Gln-Lys-Arg-Ala-Phe-Ile-Arg-Ser-Leu-Tyr-Asp-Asp- Pro-Ser-Gln-Ser-Ala-Asn-Leu-Leu-Ala-Glu-Ala-Lys-Lys-Leu-Asn-Asp-Ala-Gln-Ala- Pro-Lys-Asn-Asp-Arg-Gly-Gly-Gly-R2(Ⅱ)Wherein, R2Expression be
- 3. the medicine box according to claim 2 for being used to prepare formula (I) compound represented, which is characterized in that the medicine box Reagent include: 1~5 molar part formula (II) compound represented and 1 molar part alchlor.
- 4. the medicine box according to claim 2 or 3 for being used to prepare formula (I) compound represented, which is characterized in that the medicine The reagent of box further include: Acetic acid-sodium acetate buffer.
- 5. the medicine box according to claim 4 for being used to prepare formula (I) compound represented, which is characterized in that the acetic acid- Sodium-acetate buffer is 0.4~0.6mol/L, and pH is 3.0~5.0.
- 6. a kind of preparation method of medicine box as claimed in claim 4, which comprises the following steps:(1) formula (II) compound represented of selected molar part is dissolved in the Acetic acid-sodium acetate buffer, obtains solution A, it is standby With；(2) aluminium chloride of selected molar part is dissolved in the Acetic acid-sodium acetate buffer, obtains solution B, it is spare；(3) solution A and the solution B are uniformly mixed, obtain solution C, it is spare；(4) solution C is sterile filtered, is sub-packed in container, freeze-drying to get.
- 7. application of the described in any item medicine boxs of claim 3-5 in preparation formula (I) compound represented.
- 8. a kind of preparation method of formula (I) compound represented, which comprises the following steps:(a) acetic acid solution is added into the described in any item medicine boxs of claim 3-5, is dissolved, acetonitrile is then added and matched 's18F aqueous solution, 5~20min of confined reaction at 80~110 DEG C is cooling, obtains reaction solution；(b) water dilution is added in the reaction solution, injection Sep-Pak C18 separates pillar, rinses the Sep- with PBS and water Pak C18 separates pillar, obtains marked product；(c) with marked product described in ethanol elution, with normal saline dilution, be sterile filtered to get.
- 9. the preparation method of formula (I) compound represented according to claim 8, which comprises the following steps:(a) acetic acid solution that 10~50 μ L mass fractions are 2~8% is added to the described in any item medicine boxs of claim 3-6 In, dissolution, is then added 100~400 μ L acetonitriles and 100~200 μ L are the 20~150mCi matched18F aqueous solution, 80~110 5~20min of confined reaction at DEG C, it is cooling, obtain reaction solution；(b) water dilution is added in the reaction solution, injection Sep-Pak C18 separates pillar, rinses the Sep- with PBS and water Pak C18 separates pillar, obtains marked product；(c) marked product described in 0.2~1mL ethanol elution, with normal saline dilution, be sterile filtered to get.
- 10. formula (I) compound represented or the described in any item medicine boxs of claim 3-5 are preparing answering in PET imaging agent With.
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| CN201610144196.0A CN105884868B (en) | 2016-03-14 | 2016-03-14 | It is a kind of18The affinity body class compound and the preparation method and application thereof of F label |
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| CN105884868B true CN105884868B (en) | 2019-07-16 |
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