CN114703194B - Fluorine-18 labeled CD63 targeted compound and preparation method and application thereof - Google Patents
Fluorine-18 labeled CD63 targeted compound and preparation method and application thereof Download PDFInfo
- Publication number
- CN114703194B CN114703194B CN202210570411.9A CN202210570411A CN114703194B CN 114703194 B CN114703194 B CN 114703194B CN 202210570411 A CN202210570411 A CN 202210570411A CN 114703194 B CN114703194 B CN 114703194B
- Authority
- CN
- China
- Prior art keywords
- compound
- targeting
- xapf
- fluorine
- synthesis
- 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.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/115—Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0491—Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Optics & Photonics (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention discloses a CD63 targeting compound marked by fluorine-18 18 F]XAPF and a process for producing the same, which comprises targeting an aptamer X of CD63, linking the 5' end of X with an ethylamino group, and use of the compound 18 F]SFB reacts with 5' terminal ethylamine to obtain a fluorine-18 labeled CD63 targeting compound, and the specific structural formula is as follows:
wherein X is an aptamer serving as a CD63 targeting group, and an ethylamino group is used for radiolabelling 18 F]SFB reacts with ethylamine group in aptamer and is introduced 18 F a radioactive signal group. The CD63 targeted PET probe has excellent biological performance, has higher signal-to-noise ratio in pancreatic cancer tumor with high expression of CD63, and has stronger specificity in tumor uptake. These results are set forth in 18 F]XAPF has good clinical transformation and application prospect in the aspect of tumor PET imaging.
Description
Technical Field
The invention belongs to the technical field of medical imaging, and particularly relates to a fluorine-18 labeled CD63 targeted compound, and a preparation method and application thereof.
Background
CD63 is an important lysosome transmembrane protein and is involved in the exchange of genetic information between tumor cells and basal cells, so that a large number of new blood vessels are generated, and the growth and invasion of tumors are promoted. Thus, overexpression of CD63 is often associated with strong tumor invasiveness, poor prognosis, and high chance of metastasis and recurrence. It can be seen that tracing CD63 will facilitate an understanding of the neoplastic disease and its progression. However, there is currently a lack of reliable visualization strategies to enable visualization studies of CD 63.
The nuclear medicine imaging technology represented by PET and SPECT breaks through the wall barriers of low penetration depth of optical imaging and electron microscope, low MRI and CT imaging sensitivity and the like, and is a real oneAn ideal technology for targeted imaging of CD63 is available. PET has higher sensitivity and spatial resolution than SPECT and can perform accurate quantification, thus being more suitable for in vivo targeted imaging studies of CD 63. The invention uses the self-screened CD63 targeting aptamer X as a CD63 targeting group, the 5' end of the self-screened CD63 targeting aptamer X is connected with an ethylamino group, and then the invention uses 18 F]SFB and ethylamino in X are subjected to chemical reaction to successfully obtain a CD63 targeting compound 18 F]XAPF. The experiment proves that 18 F]XAPF has high radiochemical yield and purity, and good stability in physiological saline and ethanol. More importantly, in the mouse model of pancreatic cancer bearing tumor with high expression of CD63, the pair of tumors 18 F]XAPF has high uptake and low background uptake, and is a tumor pair 18 F]The uptake of XAPF can be effectively inhibited by the X5 nucleic acid aptamer, demonstrating that the CD63 targeting compound 18 F]Specificity of XAPF. In addition, the term 18 F]The preparation method of XAPF is simple, has low cost, and is expected to realize clinical transformation and application.
Disclosure of Invention
The primary object of the present invention is to provide a fluorine-18 labeled CD63 targeting compound.
It is another object of the present invention to provide a method for preparing the above fluorine-18 labeled CD63 targeting compound.
Still another object of the present invention is to provide the use of the above fluorine-18 labeled CD63 targeting compound for the preparation of an agent for positron emission tomography.
The specific technical scheme of the invention is as follows:
wherein, the specific structural formula of the fluorine-18 labeled CD63 targeting compound is as follows:
x is CD63 targeting aptamer X1 or X2 or X3 or X4 or X5; 18 f is a radioactive signal group; the CD63 targeting aptamer is selected from any one of X1, X2, X3, X4 and X5. The nucleotide sequence of X1 is shown as SEQ ID NO. 1; the nucleotide sequence of X2 is asSEQ ID NO. 2; the nucleotide sequence of X3 is shown as SEQ ID NO. 3; the nucleotide sequence of X4 is shown as SEQ ID NO. 4; the amino acid sequence of X5 is shown in SEQ ID NO. 5.
A method for synthesizing and labeling a fluorine-18 labeled CD63 targeting compound, comprising the steps of:
(1) synthesis of Compound 1: 4- (dimethylamino) ethyl benzoate (EDB) and methyl trifluoromethanesulfonate are used as raw materials to react at room temperature to obtain a compound 1;
(2) synthesis of Compound 2: carrying out fluorination reaction on the compound 1 to obtain a compound 2;
(3) synthesis of Compound 3: the compound 2 is reacted under the action of sodium hydroxide and hydrochloric acid to obtain a compound 3;
(4) compound 4 (, [ 2 ] 18 F]Synthesis of SFB): the compound 3 is reacted with tetrapropylamine hydroxide and 2-succinimidyl-1, 1,3, 3-tetramethyluronium tetrafluoroborate (TSTU) to give a compound 4 (, a 18 F]SFB）；
(5) Synthesis of Compound 5: aptamers X1, X2, X3, X4 and X5 in the compound 5 are obtained by screening, and an ethylamino group is connected to the 5' end of each aptamer and is used for radiolabeling;
（6）[ 18 F]synthesis of XAPF: adding compound 5 to compound 4, reacting at 40 deg.C for 20 min, and separating and purifying to obtain [ 2 ], [ 18 F]XAPF；
The fluorine-18 labeled CD63 targeting compound [ alpha ], [ beta ], [ alpha ], [ beta ] -18 18 F]XAPF is a PET imaging agent used for early diagnosis and efficacy assessment of CD63 positive tumors.
The beneficial effects of the invention are:
(1) a fluoro-18 labeled CD63 targeting compound of the present invention 18 F]XAPF, a novel CD 63-targeted PET imaging agent. [ 18 F]The preparation method of XAPF is simple and easy, has high radiochemical yield and radiochemical purity, has good stability in physiological saline and ethanol, and can be used for in vivo PET imaging of CD63 positive tumors.
(2) A fluorine-18 labeled CD63 targeting compound of the present invention 18 F]XAPF has excellent biological properties. In the tumor-bearing mouse model with high expression of CD63, the tumor pair 18 F]XAPF has high uptake as well as low background uptake, and uptake is specific, satisfying the conditions for use as a CD63 targeting PET probe.
Drawings
FIG. 1 is a composite circuit diagram of the present invention.
FIG. 2 is a schematic view of a cross-sectional view of a cross-section of a cross-sectional view of a cross-section of a cross-sectional view of a cross-section of 18 F]HPLC analysis of XAPF and Label precursor X5 [ 2 ] 18 F]The peak appearance time of XAPF and X5 on HPLC is similar to that of [ 2 ], confirmation 18 F]XAPF is successfully flagged.
FIG. 3 is a radio-TLC analysis of CD63 targeting PET probe [ 2 ] 18 F]Stability of XAPF in physiological saline and ethanol.
FIG. 4 is a diagram of a CD63 targeted PET probe [ 2 ] with or without co-injection of an X5 nucleic acid aptamer 18 F]PET imaging of XAPF in CFPAC1 tumor-bearing nude mice (as shown by a), circles and arrows indicate tumors; and in tumor 18 F]Comparison of XAPF uptake (as shown in b); tumor and muscleRatio of uptake (as shown in c).
Detailed Description
The invention will be further elucidated and described with reference to the embodiments and the accompanying description.
As shown in FIG. 1, a fluorine-18 labeled CD63 targeting compound [ 2 ] based on a CD63 targeting aptamer X5 18 F]The preparation steps of XAPF are as follows:
(1) synthesis of Compound 1:
0.9g (3.5 mmol) of ethyl 4- (dimethylamino) benzoate (EDB) was dissolved in 10 mL of dichloromethane, and then 0.4 mL (3.5 mmol) of methyl trifluoromethanesulfonate was added thereto, sealed, and reacted at room temperature for about 20 hours. After the reaction was complete, the solvent was evaporated and the pure product was obtained by twice recrystallization from dichloromethane/n-hexane, weighing 1.36g and giving a yield of 84%.
(2) Synthesis of Compound 2:
18 F - the aqueous solution was freed of the enriched fraction by Sep-Pak QMA anion exchange cartridge (water) 18 Water of O, 1.5 mL of K 222 /K 2 CO 3 (13 mg K 222 , 3 mg K 2 CO 3 Dissolved in 90% acetonitrile) of water 18 F - Eluting into a Mini-visual tube of 5 mL, azeotropically drying twice at 116 ℃, and evaporating the solvent to generate anhydrous K 222 /K[ 18 F]A complex. Drying the mixture in a container 18 F - The reaction flask of (1) was charged with compound 1 (10 mg, 31.2 μmol, dissolved in 0.2 mL of anhydrous acetonitrile), and heated at 80 ℃ for 10 min to obtain compound 2.
(3) Synthesis of Compound 3:
after cooling the reaction mixture, 0.5 mL of 0.5 mol/L NaOH was added, the reaction mixture was reacted at 90 ℃ for 5 min, and then cooled, and 0.7 mL of 1 mol/L HCl was added. The reaction solution is passed through an activated Sep-Pak C18 column, rinsed with 2 mL of 0.01 mol/L hydrochloric acid, and N 2 The Sep-Pak C18 column was blown dry and then eluted with 3 mL of acetonitrile to give Compound 3.
(4) Compound 4 (, [ 2 ] 18 F]Synthesis of SFB):
to the acetonitrile solution of Compound 3 was added 20. mu.L tetrapropyl hydroxideAn aqueous amine solution was azeotropically dried at 100 ℃ and then 12 mg of TSTU (dissolved in 0.25 mL of acetonitrile) was added thereto and reacted at 80 ℃ for 5 min. Acidified with 3 mL of 5% acetic acid and finally diluted with 6 mL of water. The solution was passed through an activated Sep-Pak C18 column, rinsed first with 10 mL acetonitrile/water (V: V =1:3) mixture, and then with N 2 Blow-drying the Sep-Pak C18 column, and finally eluting with 2 mL of anhydrous acetonitrile to obtain the compound 4 (,) 18 F]SFB) in acetonitrile. [ 18 F]The retention time of SFB on HPLC was 15.49 min, which is compared with the nonradioactive reference substance of N-hydroxysuccinimide p-formylbenzoate 19 F]The retention time (15.29 min) on HPLC of SFB (commercially available, CAS: 60444-78-2) was similar, and hence it was considered that 18 F]SFB was successfully flagged.
(5) Synthesis of Compound 5:
the aptamer X5 in Compound 5 was obtained by screening and was linked to an ethylamino group at its 5' end.
（6）[ 18 F]Synthesis of XAPF:
1 mg of Compound 5 was added to an acetonitrile solution of Compound 4, and the mixture was mixed and reacted at 40 ℃ for 20 min. And separating by HPLC under the conditions: purification was performed using a semi-preparative XBridge OST column (2.5 μ M, 50 × 10 mm, Waters) with acetonitrile and 0.1M triethylammonium acetate (TEAA) buffer as mobile phase, with a mobile phase gradient: 0-3 minutes: 0% acetonitrile, 3-12 minutes: 5-30% acetonitrile, 12-15 minutes: 30-90% acetonitrile at a flow rate of 5 mL/min. The resulting product solution was blow dried with a nitrogen blower. As shown in FIG. 2, [ alpha ], [ beta ], [ alpha ] is shown in FIG. 2 18 F]The retention time of the aptamer X5 of XAPF [ 2 ], [ precursor of a marker ] on HPLC is similar to that of 18 F]XAPF is successfully flagged. At the same time measure 18 F]The radiochemical yield of XAPF is 87.5%, [ 2 ] 18 F]Radiochemical purity of XAPF > 98%.
The above [ 2 ] 18 F]The XAPF developer is taken as an example, and the experimental result shows that the basic performance is as follows:
（1）[ 18 F]stability of XAPF in physiological saline and ethanol
The two systems of normal saline and ethanol are selected for the [ alpha ], [ beta ] -state 18 F]The in vitro stability of XAPF was studied. A certain amount of the product of the above method is required for monitoring the stability in physiological saline or ethanol 18 F]XAPF is dissolved in physiological saline or ethanol, incubated at room temperature for 0.5, 1 and 2 hours, and monitored by TLC 18 F]Radiochemical purity of XAPF to determine whether it is stable. As shown in FIG. 3, [ 2 ] 18 F]XAPF remained stable when incubated in saline and ethanol for 2 hours.
（2）[ 18 F]PET imaging of XAPF in pancreatic cancer bearing mice
Balb/c nude mice 8 weeks old were selected and right legs were seeded with CD63 positive CFPAC1 pancreatic cancer cells. PET imaging was carried out when the tumor grew to a diameter of 0.5 to 1 cm, and about 0.4 mCi/200. mu.L of the conjugate was injected into each nude mouse through the tail vein 18 F]XAPF injection, co-injected or not with X5 aptamer, and subjected to inhalational anesthesia with isoflurane 1 hour after injection, and subjected to static PET scan after prone immobilization. The pancreatic cancer tumor-bearing mouse 18 F]The result of XAPF-PET development is shown in FIG. 4, and it is understood from the result of development 18 F]XAPF is highly enriched in CD 63-positive CFPAC1 pancreatic cancer tumors and also has a high tumor to muscle ratio, suffice to say 18 F]The XAPF has high targeting effect on CD63 positive tumors.
In contrast 18 F]The result of co-injection of XAPF with an X5 nucleic acid aptamer showed that X5 nucleic acid aptamer was effective in inhibiting [ 2 ] 18 F]The intake of XAPF is fully explained 18 F]XAPF has high specificity for CD63 positive tumors.
The above description is only a preferred embodiment of the present invention, and therefore should not be taken as limiting the scope of the invention, which is defined by the appended claims.
Sequence listing
<110> secondary fifth Hospital of Zhongshan university
<120> fluorine-18 labeled CD63 targeting compound and preparation method and application thereof
<160> 5
<170> SIPOSequenceListing 1.0
<210> 1
<211> 25
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 1
gggggatgga gggtgggtcg tatat 25
<210> 2
<211> 19
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 2
accttggctg tcgtgttgt 19
<210> 3
<211> 19
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 3
aggtcagtgg tcagagcgt 19
<210> 4
<211> 19
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 4
accttggctg tcgtgttgt 19
<210> 5
<211> 19
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 5
acgctctgac cactgacct 19
Claims (3)
1. A fluorine-18 labeled CD63 targeting compound characterized by: the structural formula is
Wherein, X is CD63 targeting aptamer X5; 18 f is a radioactive signal group; the amino acid sequence of the CD63 targeting aptamer X5 is shown as SEQ ID NO. 5.
2. The method of claim 1 for preparing a fluorine-18 labeled CD63 targeting compound, comprising the steps of:
(1) synthesis of Compound 1: 4- (dimethylamino) ethyl benzoate (EDB) and methyl trifluoromethanesulfonate are used as raw materials to react at room temperature to obtain a compound 1;
(2) synthesis of Compound 2: carrying out fluorination reaction on the compound 1 to obtain a compound 2;
(3) synthesis of Compound 3: the compound 2 is reacted under the action of sodium hydroxide and hydrochloric acid to obtain a compound 3;
(4) compound 4[ alpha ], [ alpha ] and a 18 F]Synthesis of SFB: the compound 3 is reacted with tetrapropylamine hydroxide and 2-succinimidyl-1, 1,3, 3-tetramethyluronium tetrafluoroborate (TSTU) to give a compound 4[ deg. ], ] 18 F]SFB；
(5) Synthesis of Compound 5: the aptamer X5 in the compound 5 is obtained by screening, and is connected with an ethylamine group at the 5' end for radioactive labeling;
（6）[ 18 F]synthesis of XAPF: adding compound 5 to compound 4, reacting at 40 deg.C for 20 min, separating and purifying to obtain [ alpha ], [ beta ] -amino-carboxylic acid 18 F]XAPF;
3. Use of a fluorine-18 labeled CD63 targeting compound according to claim 1 or 2 for the preparation of an agent for positron emission tomography.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210570411.9A CN114703194B (en) | 2022-05-24 | 2022-05-24 | Fluorine-18 labeled CD63 targeted compound and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210570411.9A CN114703194B (en) | 2022-05-24 | 2022-05-24 | Fluorine-18 labeled CD63 targeted compound and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114703194A CN114703194A (en) | 2022-07-05 |
| CN114703194B true CN114703194B (en) | 2022-09-02 |
Family
ID=82176749
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210570411.9A Active CN114703194B (en) | 2022-05-24 | 2022-05-24 | Fluorine-18 labeled CD63 targeted compound and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114703194B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012094334A1 (en) * | 2011-01-04 | 2012-07-12 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | One-step 18f labeling of biological substrates and uses of 18f labeled biological substrates |
| CN110621351A (en) * | 2017-04-26 | 2019-12-27 | 因特欧力多公司 | Biomolecule imaging method using aptamers |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8487077B2 (en) * | 2008-09-16 | 2013-07-16 | The Regents Of The University Of California | Simplified one-pot synthesis of [18F]SFB for radiolabeling |
| WO2018199607A1 (en) * | 2017-04-26 | 2018-11-01 | 인터올리고 주식회사 | Biomolecule imaging method using aptamer |
| CN108866061A (en) * | 2018-06-21 | 2018-11-23 | 中山大学附属第五医院 | A kind of aptamer identifying liver cancer cells and its screening technique and purposes |
-
2022
- 2022-05-24 CN CN202210570411.9A patent/CN114703194B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012094334A1 (en) * | 2011-01-04 | 2012-07-12 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | One-step 18f labeling of biological substrates and uses of 18f labeled biological substrates |
| CN110621351A (en) * | 2017-04-26 | 2019-12-27 | 因特欧力多公司 | Biomolecule imaging method using aptamers |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114703194A (en) | 2022-07-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112194651B (en) | Precursor compound of PET tracer and application thereof | |
| US9550001B2 (en) | Compositions, methods of synthesis and use of carbohydrate targeted agents | |
| CN107353323B (en) | Al18F-labeled PSMA (PSMA) targeted inhibitor and preparation method and application thereof | |
| KR20110038725A (en) | Psma-binding agents and uses thereof | |
| JP5732198B2 (en) | Method for producing radioactive fluorine-labeled organic compound | |
| CN113292538A (en) | Compound of targeting tumor-associated fibroblast activation protein, preparation method and application thereof, and tumor developer targeting FAP | |
| JPS58126887A (en) | Novel 7-deazapurine derivative | |
| CN111909105B (en) | Prostate specific membrane antigen inhibitor, metal marker thereof, preparation method and application | |
| CN115010629B (en) | Prostate specific membrane antigen inhibitor, nuclide marker, preparation method and application | |
| CN117624278B (en) | Specific tumor diagnosis probe and imaging agent for targeting heat shock protein 90 | |
| CN113548986B (en) | Sulfonyl fluoride compound and application thereof | |
| CN116751258B (en) | MDM2/MDMX targeting polypeptide and application thereof | |
| CN114703194B (en) | Fluorine-18 labeled CD63 targeted compound and preparation method and application thereof | |
| AU5215100A (en) | Methods for preparing perfluorinated (18F)-radiolabelled nitroimidazole derivatives for cellular hypoxia detection | |
| CN114573558B (en) | Water-soluble methyl benzyl ether derivative, positron nuclide probe, nuclide marker, preparation method and application | |
| WO2010131745A1 (en) | 18f-labeled azide compound, reagent for 18f-labeling and method for 18f-labeling of alkyne compound using same | |
| CN114031652B (en) | Glucose derivative containing cyclohexane and application thereof | |
| PL239934B1 (en) | Derivatives of PSMA inhibitors for ⁹⁹ᵐTc labelling by HYNIC, radiopharmaceutical kit, radiopharmaceutical preparations and their use in the diagnosis of prostate cancer | |
| Wester | 42 18 F: Labeling Chemistry and Labeled Compounds | |
| CN113368264B (en) | Radiolabeled cinnamycin, preparation method and application thereof | |
| CN113861254A (en) | Tumor PET imaging agent68Ga-NOTA-ADG and preparation method and application thereof | |
| CN115368342B (en) | Fibroblast active protein inhibitor, radionuclide marker, preparation method and application thereof | |
| CN114853827B (en) | Glucose derivative ligand compound and preparation method and application thereof | |
| CN112961173B (en) | Prostate specific membrane antigen targeted molecular probe, preparation method and application thereof | |
| CN112250680B (en) | Novel berberine derivative and synthesis method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |