CN114853732A - Radionuclides 18 Preparation method of F-labeled FAPI compound, compound prepared by preparation method and application of compound - Google Patents
Radionuclides 18 Preparation method of F-labeled FAPI compound, compound prepared by preparation method and application of compound Download PDFInfo
- Publication number
- CN114853732A CN114853732A CN202111607873.5A CN202111607873A CN114853732A CN 114853732 A CN114853732 A CN 114853732A CN 202111607873 A CN202111607873 A CN 202111607873A CN 114853732 A CN114853732 A CN 114853732A
- Authority
- CN
- China
- Prior art keywords
- fapi
- reaction
- nota
- compound
- preparation
- 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.)
- Withdrawn
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
- A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
- A61K51/0482—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group chelates from cyclic ligands, e.g. DOTA
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Optics & Photonics (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a radionuclide 18 A process for preparing F-labeled FAPI compound includes adding NOTA-FAPI precursor, acetate buffer solution, anhydrous acetonitrile, AlCl and the mixture to the micro-reactor with precise control of reaction progress 3 Acetate buffer solution and [ 2 ] 18 F]Carrying out sealing reaction on the fluorine ion liquid; accurately detecting color change through a sensor, timely and continuously introducing the reaction liquid into a cooling module for cooling, and diluting a reaction system with deionized water; introducing the diluted reaction solution into a purification module, separating and purifying by using a C18 column, then leaching by using 50-80% ethanol, and filtering by using a 0.22 mu m filter membrane to obtain the target with stable performanceCompound Al 18 F‑NOTA‑FAPI04。
Description
Technical Field
The application relates to the technical field of radiopharmaceutical labeling, in particular to a preparation method of a compound with radioactive nuclide 18F labeled FAPI, and the prepared compound and application thereof.
Background
Fibroblast Activation Protein (FAP) is a membrane-anchored peptidase belonging to the dipeptidyl peptidase 4 (DPP 4) family, having dipeptidyl peptidase and endopeptidase activities, and having 52% homology with DPP4 at the protein level. FAP can be expressed on the surfaces of tumor interstitial cells, macrophages and tumor cell membranes, and is highly expressed in more than 90% of epithelial tumors. Research shows that FAP protein has extremely low expression in healthy tissues, obviously increases expression in pathological states of tissue remodeling and repair parts, and relates to various clinical diseases such as cardiovascular diseases, arthritis, lung fibrosis and the like. FAP directly promotes proliferation, migration, and invasion of mesenchymal fibroblasts and other types of cells, including tumors, endothelial cells, and immune cells, leading to invasiveness, tumor neovascularization, and evasion of immune surveillance. FAP is a biomarker with great potential to reflect the characteristics of the tumor microenvironment, the tumor treatment target and the predicted curative effect. Therefore, Fibroblast Activation Protein Inhibitors (FAPI) and derivatives thereof can be labeled with radionuclides for PET imaging studies.
The FAPI PET imaging reported in the literature at present is mostly composed of 68 Ga-labelled, has the following disadvantages: firstly 68 Ge/ 68 The yield of the Ga generator per elution is low; secondly, the half-life period is short (68min), the storage time is short, and long-distance transportation is not facilitated; checking diseasesWhen the number of people is large, multiple generators need to be produced for multiple times, the cost is high, and the radiation protection of operators is not facilitated. 18 F-labeled FAPI-04 has fewer reports, 18 f is produced by a cyclotron and can be used for marking FAPI and comparing 68 Ga, which has the following advantages: long half-life (110 min); ② 18 Energy comparison of F positron 68 The Ga nuclide has higher spatial resolution; the accelerator is popularized domestically, the occupancy rate of the fluorine mark is high, and the later-stage popularization is facilitated.
Chinese patent (CN202011085122.7) discloses a 18 A method for preparing F-labeled biomarker by reacting a solution of precursor compound such as P-FAPI, NOTA-FAPI or NCS-FAPI with 18 F - Ion, reacting under heating to obtain 18 The F-labeled biomarker has high reaction difficulty, complete substitution is difficult to ensure, and the prepared product has low yield, low purity and poor stability;
chinese patent (CN201710962001.8) also discloses a similar method, wherein precursor solution with complex structure is mixed with 18 F - The ions are mixed and reacted by 18 F instead of hydrogen in the precursor 18 F-labeled biomarkers, the method also has the disadvantages, and the preparation process of the precursor compounds is complicated;
chinese patent (CN201410188163.7) discloses Exenatide 18 F label, first prepared 18 F - FBEM, get 18 Dissolving F-FBEM in acetonitrile, adding Cys39-Exenati PBS buffer solution, performing coupling reaction at room temperature, and purifying by preparative HPLC to obtain target product 18 F - FBEM-Cys 39-Exenatide. The technical scheme has complex preparation process, long time consumption and difficulty in ensuring the purity and stability of the product;
chinese patent (CN202011269249.4) discloses 18F-labeled Al by chelating chemistry 18 Scheme of F-FAPI, Al is prepared first 18 F solution, then DOTA and NOTA are mixed to prepare precursor solution with cyclic coordination groups, and then the precursor solution is subjected to mixing reaction, purification and filtration to obtain a product, wherein the product is obtained by utilizing Al 3+ Ion pair 18 F ionAnd cyclic coordination groups (DOTA and NOTA) to synthesize and prepare the Al 18 F - FAPI has a radiochemical purity of more than 99%. In order to improve the yield and the purity of the product, the chelating ability is improved by preparing a precursor solution of a cyclic coordination group with strong chelating ability, so that the yield, the purity and the stability of the product are improved, but the preparation cost of the precursor of the cyclic coordination group is higher, and Al is contained in the practical use process 18 F-NOTA-FAPI needs to be prepared on site at present, the reaction speed of chelation reaction is high, if experiments are carried out only by means of fixed reaction time, the quality of obtained products is uneven because the actual reaction end point cannot be judged in different experiments, and the stability, yield and purity of the products are difficult to guarantee.
Based on the problems in the prior art, if the reaction process can be accurately determined, the stability of the reaction product tends to be uniform, and the product is ensured to be used for stable radiochemical purity and specific activity, so that better application effect and economic benefit can be obtained. Therefore, a novel method with high yield, high efficiency, high quality and low cost is developed 18 The F-labeled FAPI method has important use significance for PET imaging in practical application.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a radionuclide 18 A process for the preparation of a compound labeled FAPI comprising the steps of;
1) providing radionuclides 18 The F-marked FAPI micro-reaction device comprises 2 feeding pipes and 1 detection rod, wherein the detection rod is made of hollow transparent high-strength toughened glass, and is internally provided with a photosensitive sensor which is connected with a display instrument through a line; indicators are attached to the surfaces of the detection rods, and then an ionic membrane through which metal ions pass is coated outside the detection rods; the ionic membrane can enable metal ions to enter the ionic membrane to react and develop color in a contact way with an indicator, and the indicator with high molecular weight cannot penetrate through the ionic membrane to enter a liquid phase reaction system;
2) adding a NOTA-FAPI precursor through a feed pipe (1); mixing acetate buffer solution and anhydrous acetonitrile、AlCl 3 An acetate buffer solution, which is supplied through the supply pipe (2) 18 F]Sealing the fluorine ion solution after the feeding is finished, starting heating reaction at the temperature of 90-150 ℃, simultaneously observing the color change of the indicator through a display instrument, immediately stopping the heating reaction once the color changes, and adding deionized water into the micro-reaction device to dilute the reaction system for cooling; leading out reaction liquid from the micro-reaction device, entering a purification module, separating by using a C18 column in the purification module, and filtering to obtain a target compound Al 18 F-NOTA-FAPI 04; NOTA-FAPI precursor and AlCl in the raw materials 3 Acetate buffer solution and [ 2 ] 18 F]Adding the fluoride ion solution according to the stoichiometric ratio and slightly excessive aluminum chloride; the indicator can be selected from the commonly used aluminum ion indicators in the prior art, and the chelating capacity of the aluminum ion indicator to aluminum ions is lower than that of the NOTA-FAPI precursor to the aluminum ions.
Specifically, the term 18 F]The preparation method of the fluorine ion solution comprises the following steps:
by nuclear reactions 18 O(p,n) 18 F, production of [ alpha ], [ beta ] in a cyclotron 18 F]The fluorine ion oxygen-rich aqueous solution, and then the fluorine ion oxygen-rich aqueous solution is transferred to the QMA column after activation (the QMA column is activated using physiological saline and water in this order), [ 2 ] 18 F]The fluoride ion is enriched on the QMA column, the QMA column is rinsed with physiological saline, and the thus-obtained product is collected 18 F]And (4) fluorine ion liquid.
Specifically, the raw material is added into 100-500 mu g NOTA-FAPI precursor by adding 60-300 mu L0.1M acetate buffer solution (pH 4), 200-600 mu L anhydrous acetonitrile, 6-20 mu L10 mM AlCl 3 Acetate buffer solution (pH 4) and 100. mu.L of [ sic ], [ solution ] 18 F]And (4) fluorine ion liquid.
Specifically, the detection rod is attached with an indicator and is prepared by adopting processes such as spraying, printing and the like.
Specifically, the indicator can be an aluminum ion indicator in the prior art, and the chelating capacity of the aluminum ion indicator to aluminum ions is lower than that of the NOTA-FAPI precursor to aluminum ions.
Specifically, the NOTA-FAPI precursor is stored in the container as a cold dry powder using a freeze-drying process.
Specifically, the step of separating the reaction solution diluted in the purification module by using a C18 column means that the diluted reaction solution passes through an activated C18 column (activated by ethanol and deionized water in sequence and dried by air), and the column is washed by deionized water to remove free reaction solution 18 F-and Al 18 F 2+ And then leaching with ethanol.
Specifically, the filtration is performed by diluting the reaction solution obtained by dilution with a C18 column, separating the resultant with physiological saline, and passing the diluted product through a 0.22 μm sterile filter.
The invention also provides a radionuclide 18 F is marked with FAPI and is prepared by the preparation method.
The invention also provides a tracer which comprises the radionuclide 18 F a compound labeling FAPI.
The invention also provides a radionuclide 18 The preparation method of the F-labeled FAPI compound and the application of the compound prepared by the preparation method in the field of preparation of the tracer, in particular, the tracer can be used for detecting tumors, myocardial injuries and inflammatory diseases.
Radiochemical purity of the final product was determined by HPLC with a retention time of 6.3min, Al 18 The F-NOTA-FAPI04 has an amplification purity of over 99.5% and a specific activity of about 20 GBq/. mu.mol.
Compared with the prior art, the invention has the following beneficial effects:
1) the invention is provided with a special micro-reaction device, a detection rod is made of hollow transparent high-strength toughened glass, a photosensitive sensor is arranged in the detection rod, and the photosensitive sensor is connected with a display instrument through a circuit; indicators are attached to the surfaces of the detection rods, and then an ionic membrane through which metal ions pass is coated outside the detection rods; the indicator can be an aluminum ion indicator in the prior art, the chelating capacity of the aluminum ion indicator to aluminum ions is lower than that of fluorine ions and NOTA-FAPI precursors, and in the reaction process, the aluminum ions preferentially react with the fluorine ions to generate Al 18 F, then continuing the NOTA-FAPI precursor to the target compoundAl 18 F-NOTA-FAPI04, once the reaction is complete, redundant aluminum ions are chelated with an aluminum ion indicator to cause the color of the indicator to change, and the reaction is stopped immediately at the moment, so that the reaction time is saved, the generation of impurities caused by continuous reaction is avoided, the purity of the product is ensured, and the difficulty of subsequent purification is reduced; in the prior art, the reaction end point is usually judged by directly adding a display agent or adding a display agent into reaction supernatant, wherein the former is easy to introduce new impurities, and the latter cannot accurately judge the reaction end point in time; in addition, the application is more accurate than naked eye observation in detection through a precise sensor;
2) the invention mixes the raw materials for reaction by a one-step method, has shorter process flow, lower cost and higher efficiency, and ensures the yield 18 F]In solution of fluoride ion 18 Conversion of F to Al 18 The conversion rate of F-NOTA-FAPI-04 is more than 99 percent;
3) the method ensures the purity and stability of the product by controlling the reaction process, and further improves the preparation efficiency by combining the FAPEPT developer and the quantitative kit; al prepared by the method 18 The F-NOTA-FAPI-04 has radiochemical purity of over 99.5 percent, has stable product performance, realizes the aim of instant use, ensures the uniform standard of the use performance of the product and meets the clinical requirement.
Drawings
FIG. 1 is a process formula of a target compound prepared in example 1.
FIG. 2 is a flow chart of the preparation of example 1.
FIG. 3 preparation of radionuclide in example 1 18 F marks the specific composition of the micro-reaction device of FAPI.
Wherein: 1. a micro-reaction device; 2. a detection rod; 3. a feed pipe (1); 4. a feed pipe (2); 5. and a display instrument.
FIG. 4 shows Al in example 4 18 HPLC profile of F-NOTA-FAPI-04 compound.
FIG. 5 shows Al in example 5 18 In vitro stability assay of F-NOTA-FAPI-04 Compounds.
FIG. 6 is the biological profile of AlF-NOTA-FAPI-04 in example 6 in tumor-bearing nude mice.
FIG. 7 shows Al obtained in example 7 18 F-NOTA-FAPI-04 compound is used for U87MG tumor-bearing nude mouse MicroPET image display, wherein, FIG. 7a is an uptake group PET image, FIG. 7b is an uptake group PET/CT fusion image, FIG. 7c is an inhibition group PET image, and FIG. 7d is an inhibition group PET/CT fusion image;
Detailed Description
The present invention will be further illustrated and described with reference to the following examples, but the examples described are only a part of the examples of the present invention, and not all of the examples. All other inventions and embodiments based on the present invention and obtained by a person of ordinary skill in the art without any creative effort belong to the protection scope of the present invention.
The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.
Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
Description of technical terms:
18 O(p,n) 18 f represents cyclotron proton bombardment H 2 18 O generation 18 F nuclide; the QMA column represents a solid phase extraction column; [ 18 F]Represents fluorine-18; GBq/. mu.mol represents 10 9 Beck per micromole; mCi represents the activity in milliCurie; column C18 represents an octadecylsilane bonded silica packing column; HPLC means high performance liquid chromatography.
Example 1, a method for preparing a radionuclide-labeled FAPI compound, comprising the steps of;
the following reagents were prepared in advance:
NOTA-FAPI-04 precursor 300. mu.g
Acetate buffer (0.1M, pH 4)60 μ L
Physiological saline 600 mu L
10mM AlCl 3 Acetate buffer 10. mu.L
Anhydrous acetonitrile 200. mu.L
1) Providing a radionuclide 18 The F marked FAPI micro-reaction device comprises a feed inlet, a discharge outlet and a mechanical rotor, wherein a rotating shaft and rotating blades of the mechanical rotor are both made of hollow transparent high-strength toughened glass, a photosensitive sensor is arranged in the mechanical rotor, and the photosensitive sensor is connected with display equipment through a line; indicator is adhered to the surfaces of the blades and the rotating shaft of the mechanical rotor, and then an ionic membrane through which metal ions pass is coated outside the indicator; the ionic membrane can enable metal ions to enter the ionic membrane to react and develop color in a contact way with an indicator, and the indicator with high molecular weight cannot penetrate through the ionic membrane to enter a liquid phase reaction system;
2) adding a NOTA-FAPI precursor through a feed pipe (1); mixed acetate buffer solution, anhydrous acetonitrile, AlCl 3 An acetate buffer solution, which is supplied through the supply pipe (2) 18 F]Sealing the fluorine ion solution after the feeding is finished, starting heating reaction at the temperature of 90-150 ℃, simultaneously observing the color change of the indicator through a display instrument, immediately stopping the heating reaction once the color changes, and adding deionized water into the micro-reaction device to dilute the reaction system for cooling; leading out reaction liquid from the micro-reaction device, entering a purification module, separating by using a C18 column in the purification module, and filtering to obtain a target compound Al 18 F-NOTA-FAPI 04; NOTA-FAPI precursor and AlCl in the raw materials 3 Acetate buffer solution and [ 2 ] 18 F]Adding the fluoride ion solution according to the stoichiometric ratio and slightly excessive aluminum chloride; the indicator can be a common aluminum ion indicator in the prior art, and the chelating capacity of the aluminum ion indicator to aluminum ions is lower than that of a NOTA-FAPI precursor to the aluminum ions.
Wherein, the [ alpha ], [ beta ] -a 18 F]The preparation method of the fluorine ion liquid comprises the following steps: by nuclear reactions 18 O(p,n) 18 F, in the production of a cyclotron 18 F]The aqueous fluorine ion-enriched solution, then 2.5mL of the aqueous fluorine ion-enriched solution having an activity of 2 to 10(54 to 270mCi) was transferred to the QMA column after activation (the QMA column was activated using 5mL of physiological saline and 10mL of water in this order), respectively 18 F]Concentrating fluorine ion on QMA column, eluting QMA column with 0.3-0.8mL physiological saline, and collecting with 1.5mL LEP tubeTo 18 F]And (4) fluorine ion liquid.
The process chemical formula of the target compound of this example is shown in FIG. 1. Radiochemical purity of the final product was determined by HPLC with a retention time of 6.3 min.
Al obtained by the process 18 F-NOTA-FAPI-04:
color: colorless;
the characteristics are as follows: a clear liquid;
pH value: 4-6;
the radiochemical purity is more than 99.5 percent;
the specific activity was about 20 GBq/. mu.mol.
Example 2 quality determination of AlF-NOTA-FAPI-04
The identification method comprises the following steps: analytical HPLC was used for quality control of the final product AlF-NOTA-FAPI-04 obtained in the examples, equipped with a UV/Vis detector preset at 220nm, an analytical C18 column and a radioactivity detector (Eckert & Ziegler, GA, USA). The column flow rate was 1ml/min and was maintained at about room temperature. The sample was eluted, mixture of mobile phase a: acetonitrile solution containing 0.1% (V: V) trifluoroacetic acid, mobile phase B: an aqueous solution containing 0.1% (V: V) trifluoroacetic acid. The elution gradient was: the content of mobile phase A increases from 5% to 40% A in 0-17min, and decreases from 40% to 5% in 17-17.5 min. The results of the product analysis of example 1 are shown in FIG. 4.
Example 3: stability identification of AlF-NOTA-FAPI-04
The identification method comprises the following steps: standing the AlF-NOTA-FAPI-04 medicament obtained in the example 1 for 1, 3 and 7 hours at room temperature, and detecting the stability of the medicament by using an HPLC analysis method; adding a small amount of AlF-NOTA-FAPI-04 drug into human serum, standing at 37 deg.C for 1, 3, and 7h, and detecting the stability of the drug in serum by HPLC analysis, the result is shown in FIG. 3.
As shown in FIG. 5, the stability identification result shows that the time-dependent HPLC (high performance liquid chromatography) profile of the AlF-NOTA-FAPI-04 drug in human serum shows that the radiochemical purity of the drug is basically maintained after the AlF-NOTA-FAPI-04 drug is kept in the human serum for 1h, 3h and 7h at 37 ℃.
Example 4: biological distribution test of AlF-NOTA-FAPI-04 in tumor-bearing nude mice
A solution of AlF-NOTA-FAPI-04 with a radiochemical purity of greater than 99.5% was prepared as in example 1. Nude mice bearing U87MG tumor (about 20g) were injected with 100 μ L (about 100 μ Ci) of drug via caudal vein, and the mice were sacrificed at 40min, 1h, 2h, and 4h, and their blood, heart, bone, liver, spleen, lung, kidney, stomach, intestine, bladder, tumor, and gallbladder tissues were weighed and counted by radioactivity using a gamma counter, and the percent injection dose rate per gram of tissue (% ID/g) was calculated, and the results are shown in FIG. 4.
As shown in FIG. 6, the results of in vivo biological distribution indicate that AlF-NOTA-FAPI-04 has good tumor specificity, high tumor uptake speed, long retention time and low non-target background uptake, and can be used for tumor imaging.
Example 5: u87MG tumor-bearing nude mouse MicroPET imaging by adopting AlF-NOTA-FAPI-04
A solution of AlF-NOTA-FAPI-04 with a radiochemical purity of greater than 99.5% was prepared as in example 1. 100 mu L (about 100 mu Ci) of the drug is injected from the tail vein of a nude mouse with U87MG tumor (about 20g), and MicroPET/CT imaging is carried out on the nude mouse with tumor at 40min, 1h, 2h and 4h respectively. To demonstrate the specificity of drug uptake, the tumor-bearing mice were imaged again by MicroPET/CT with unlabeled NOTA-FAPI-04 compounds injected 30min in advance, and the results are shown in FIG. 7.
As shown in the imaging result of FIG. 7, AlF-NOTA-FAPI-04 has obvious tumor uptake, and the tumor uptake of the inhibition group is obviously reduced, which indicates that the drug has the characteristic of tumor uptake and can be used as a novel PET imaging agent for tumor imaging.
Claims (10)
1. A radionuclide 18 A process for the preparation of a compound labelled FAPI, characterised in that it comprises the following steps;
comprises the following steps;
1) providing radionuclides 18 The F-marked FAPI micro-reaction device comprises 2 feeding pipes and 1 detection rod, wherein the detection rod is made of hollow transparent high-strength toughened glass, and is internally provided with a photosensitive sensor which is connected with a display instrument through a line; detection bar meterThe surfaces are all attached with indicators, and then the outside is coated with an ionic membrane through which metal ions pass; the ionic membrane can enable metal ions to enter the ionic membrane to react and develop color in a contact way with an indicator, and the indicator with high molecular weight cannot penetrate through the ionic membrane to enter a liquid phase reaction system;
2) adding a NOTA-FAPI precursor through a feed pipe (1); mixed acetate buffer solution, anhydrous acetonitrile, AlCl 3 An acetate buffer solution, which is supplied through the supply pipe (2) 18 F]Sealing the fluorine ion solution after the feeding is finished, starting heating reaction at the temperature of 90-150 ℃, simultaneously observing the color change of the indicator through a display instrument, immediately stopping the heating reaction once the color changes, and adding deionized water into the micro-reaction device to dilute the reaction system for cooling; leading out reaction liquid from the micro-reaction device, entering a purification module, separating by using a C18 column in the purification module, and filtering to obtain a target compound Al 18 F-NOTA-FAPI 04; NOTA-FAPI precursor and AlCl in the raw materials 3 Acetate buffer solution and [ 2 ] 18 F]Adding the fluoride ion solution according to the stoichiometric ratio and slightly excessive aluminum chloride; the indicator can be selected from the commonly used aluminum ion indicators in the prior art, and the chelating capacity of the aluminum ion indicator to aluminum ions is lower than that of the NOTA-FAPI precursor to the aluminum ions.
2. The method of claim 1, wherein the [ alpha ], [ beta ] -is 18 F]The preparation method of the fluorine ion solution comprises the following steps:
by nuclear reactions 18 O(p,n) 18 F, production of [ alpha ], [ beta ] in a cyclotron 18 F]The fluorine ion oxygen-rich aqueous solution is then transferred to the activated QMA column 18 F]The fluoride ion is enriched on the QMA column, and then the QMA column is eluted with physiological saline, collected to obtain 18 F]And (4) fluorine ion solution.
3. The process according to claim 1, wherein the starting material is added in a proportion of 60 to 300 μ L0.1M in which the acetate salt having a pH of 4 is added in a buffer solution per 100 μ g of the NOTA-FAPI precursor200- 3 Acetate buffer solution and 100. mu.L of the same 18 F]And (4) fluorine ion solution.
4. The preparation method according to claim 1 or 3, wherein the detection rod is attached with an indicator and prepared by spraying, printing and other processes.
5. The method for preparing a peptide of claim 1, wherein the purification module is used for enriching and purifying the reaction solution by using a C18 column, and the diluted reaction solution is passed through an activated C18 column, and the column is washed by deionized water to remove free peptide 18 F-and Al 18 F 2+ And then leaching by using 50-80% ethanol.
6. The method according to claim 1, wherein the filtration is performed by diluting the reaction mixture obtained by dilution with a C18 column, separating the product, diluting the product with physiological saline, and passing the product through a 0.22 μm sterile filter.
7. A radionuclide 18 A compound labeled FAPI, prepared by the preparation method of any one of claims 1 to 6.
8. A tracer, comprising the radionuclide of claim 7 18 F a compound labeling FAPI.
9. The radionuclide of any of claims 1 to 6 18 A method for the preparation of a compound labeled FAPI or the use of a compound according to claim 7 in the field of the preparation of tracers.
10. Use according to claim 9, wherein the tracer is for the detection of tumors, myocardial damage, inflammatory diseases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111607873.5A CN114853732A (en) | 2021-12-22 | 2021-12-22 | Radionuclides 18 Preparation method of F-labeled FAPI compound, compound prepared by preparation method and application of compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111607873.5A CN114853732A (en) | 2021-12-22 | 2021-12-22 | Radionuclides 18 Preparation method of F-labeled FAPI compound, compound prepared by preparation method and application of compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114853732A true CN114853732A (en) | 2022-08-05 |
Family
ID=82627509
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111607873.5A Withdrawn CN114853732A (en) | 2021-12-22 | 2021-12-22 | Radionuclides 18 Preparation method of F-labeled FAPI compound, compound prepared by preparation method and application of compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114853732A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116925041A (en) * | 2023-06-12 | 2023-10-24 | 上海交通大学医学院附属仁济医院 | Fluorine-labeled radiopharmaceuticals precursors, radiolabeled compounds, and uses thereof, targeting fibroblast activation proteins |
-
2021
- 2021-12-22 CN CN202111607873.5A patent/CN114853732A/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116925041A (en) * | 2023-06-12 | 2023-10-24 | 上海交通大学医学院附属仁济医院 | Fluorine-labeled radiopharmaceuticals precursors, radiolabeled compounds, and uses thereof, targeting fibroblast activation proteins |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111467510B (en) | Specific targeting radionuclide marker and preparation method and application thereof | |
| CN113880810B (en) | Nuclide-labeled complex and preparation method and application thereof | |
| CN113292538A (en) | Compound of targeting tumor-associated fibroblast activation protein, preparation method and application thereof, and tumor developer targeting FAP | |
| CN111905112A (en) | Polypeptide compound targeting PD-L1 and application thereof | |
| EP2334642B1 (en) | Simplified one-pot synthesis of [18f]sfb for radiolabeling | |
| WO2023246830A1 (en) | Method for preparing liquid composition of compound i and use thereof in myocardial metabolism pet imaging | |
| CN101443051A (en) | Radiolabeled gallium complexes, methods for synthesis and use for PET imaging of EGFR expression in malignant tumors | |
| CN114853732A (en) | Radionuclides 18 Preparation method of F-labeled FAPI compound, compound prepared by preparation method and application of compound | |
| Chakraborty et al. | Tracer level radiochemistry to clinical dose preparation of 177Lu-labeled cyclic RGD peptide dimer | |
| CN107308466A (en) | With tumor vascular targeted polypeptide, molecular probe and its preparation method and application | |
| CN115974962A (en) | FAP (FAP-associated protein) targeted probe as well as preparation method and application thereof | |
| CN116751258B (en) | MDM2/MDMX targeting polypeptide and application thereof | |
| CN117624278A (en) | Specific tumor diagnosis probe and imaging agent for targeting heat shock protein 90 | |
| WO2023246829A1 (en) | Liquid composition comprising compound i, preparation method and use | |
| CN117164557A (en) | Radiolabeled precursors for targeting fibroblast activation protein and radiolabeled compounds and uses thereof | |
| WO2023184839A1 (en) | Preparation of novel probe 99mtc-labeled affinity targeting tumor pd-l1 | |
| Wong | Roles of high-performance liquid chromatography in nuclear medicine | |
| CN114656390A (en) | 18Synthesis method of F-labeled benzamide receptor developer | |
| CN107847617B (en) | Metal tricarbonyl complexes containing substituted iminodiacetic acid ligands and their use as radiotracers | |
| Yousefnia et al. | Preparation and quality control of lutetium-177 bleomycin as a possible therapeutic agent | |
| CN112999369A (en) | HER2 affinity radionuclide marker composition and application thereof | |
| CN103159841B (en) | Method for marking Cys-Annexin V by use of 99mTc and application of method | |
| Jeffries | Nonisotopic Labeling | |
| WO2022193038A1 (en) | [18f]alf labeled psma targeting molecular probe and preparation method therefor | |
| Chakraborty et al. | Utilization of a novel electrochemical 90Sr/90Y generator for the preparation of 90Y-labeled RGD peptide dimer in clinically relevant dose |
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 | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20220805 |
|
| WW01 | Invention patent application withdrawn after publication |