Radionuclide 18 Method for detecting radiochemical purity of F-labelled FAPI compounds
By employing a thin-layer chromatography method using polyamide-6 plates and methanol as the developing solvent, the problem of separating 18F ions from radioactive 18F-labeled FAPI compounds in existing technologies has been solved, achieving accurate radiochemical purity detection and reducing equipment costs.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- CHINESE PEOPLES LIBERATION ARMY ARMY SPECIAL MEDICAL CENTER
- Filing Date
- 2023-04-11
- Publication Date
- 2026-04-10
AI Technical Summary
Existing thin-layer chromatography methods cannot effectively separate 18F ions from radioactive 18F-labeled FAPI compounds, resulting in the inability to accurately detect their radiochemical purity. Furthermore, high-performance liquid chromatography equipment is expensive and not conducive to widespread adoption.
Thin-layer chromatography using polyamide-6 plates and methanol as the developing solvent, combined with a specific detection probe, enables the effective separation of 18F ions from radioactive 18F-labeled FAPI compounds. Purity is determined through spotting, development, and detection steps.
It achieves efficient separation of 18F ions from radioactive 18F-labeled FAPI compounds, ensuring the accuracy and speed of detection results, and is applicable to the detection of various drugs, while reducing equipment costs.
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Figure CN116539789B_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of radiochemical purity detection, and particularly relates to a kind of radionuclide 18 The application belongs to the technical field of radiochemical purity detection, and particularly relates to a kind of radionuclide BACKGROUND
[0002] Radionuclide 18 F-labeled fibroblast activation protein inhibitors (FAPI) have been widely used in PET imaging due to their long half-life and high spatial resolution. Before using radionuclide 18 F-labeled FAPI compounds, their radiochemical purity must be determined.
[0003] In the existing technology, the detection method of radiochemical purity is high performance liquid chromatography detection method. The high performance liquid chromatography detection method has the following shortcomings: ① when 18 F ion content is low, 18 F ion may be adsorbed by the chromatographic column, resulting in inaccurate detection results; ② requires a specific chromatographic column, and the chromatographic column needs to be pre-equilibrated, which requires more time and is not conducive to switching between different drug detection. ③ High performance liquid chromatography equipment is expensive and is not conducive to comprehensive promotion. Thin layer chromatography detection method is widely used for radiochemical purity detection of radiopharmaceuticals, which has the following advantages compared with high performance liquid chromatography detection method: ① can detect 18 F ion content; ② convenient and fast, multiple drug detection does not interfere with each other; ③ thin layer chromatography detection method is widely used and conducive to comprehensive promotion. However, the existing thin layer chromatography method cannot separate 18 F ion and FAPI compound, which makes it impossible to detect radionuclide 18 F-labeled FAPI compound; therefore, it is of great significance to study a method for detecting the radiochemical purity of radionuclide 18 F-labeled FAPI compound. 18 F-labeled FAPI compound. SUMMARY
[0004] The present application aims to at least solve one of the technical problems in the related art. To this end, the main purpose of the present application is to provide a method for detecting the radiochemical purity of radionuclide 18 F-labeled FAPI compound, which realizes 18 F ion and radionuclide 18 F-labeled FAPI compound, proving the applicability of the method; overcoming the problem that the existing thin layer chromatography method is not suitable for detecting the radiochemical purity of radionuclide 18 F-labeled FAPI compound.
[0005] The object of the present application is achieved by the following technical solutions:
[0006] A radionuclide 18 The method for detecting the radiochemical purity of F-labeled FAPI compound comprises the following steps: using thin layer chromatography to detect the radionuclide 18 The method for detecting the radiochemical purity of F-labeled FAPI compound, wherein the thin layer plate is a polyamide-6 thin layer plate, and the developing agent is methanol.
[0007] The present application provides a radionuclide 18 The method for detecting the radiochemical purity of F-labeled FAPI compound, especially, by selecting a thin layer plate and a developing agent, and simultaneously increasing the detection of H 18 F solution and H 18 F and Al 18 F-NOTA-FAPI-42 mixed solution, 18 F ion and radionuclide 18 The F-labeled FAPI compound presents two spectrum peaks with good separation degree. Therefore, the method can accurately detect the radiochemical purity of the radionuclide 18 F-labeled FAPI compound.
[0008] According to the radionuclide 18 The method for detecting the radiochemical purity of F-labeled FAPI compound, wherein the radionuclide 18 F-labeled FAPI compound is Al 18 F-NOTA-FAPI-42.
[0009] According to the radionuclide 18 The method for detecting the radiochemical purity of F-labeled FAPI compound comprises the following steps:
[0010] 1) Spotting: using a quantitative capillary to respectively suck the radionuclide 18 F-labeled FAPI compound, and spotting on a polyamide-6 thin layer plate and then blowing dry or air drying with cold wind;
[0011] 2) Development: using methanol as a developing agent, sealing the development cylinder, and air drying after development is completed;
[0012] 3) Detection: using a radioactive thin layer scanner to measure and obtain radioactive counts, and analyzing the specific migration value R f And radiochemical purity.
[0013] According to the radionuclide 18The developing in step 2) can be one-time developing or two-time developing.
[0014] The radionuclide provided in the method for detecting the radiochemical purity of the F-labeled FAPI compound 18 The radionuclide in step 1) of the method for detecting the radiochemical purity of the F-labeled FAPI compound 18 The sample amount of the F-labeled FAPI compound is 2-20 μL.
[0015] The radionuclide provided in the method for detecting the radiochemical purity of the F-labeled FAPI compound 18 The methanol in the method for detecting the radiochemical purity of the F-labeled FAPI compound is analytical pure methanol, and the polyamide-6 thin layer plate is a plastic thin layer plate with a polyamide-6 thin layer on the surface.
[0016] The radionuclide provided in the method for detecting the radiochemical purity of the F-labeled FAPI compound 18 In step 3) of the method for detecting the radiochemical purity of the F-labeled FAPI compound, a beta-ray detection probe is used.
[0017] The radionuclide provided in the method for detecting the radiochemical purity of the F-labeled FAPI compound 18 The method for detecting the radiochemical purity of the F-labeled FAPI compound optimizes the conditions such as a plastic thin layer plate with a polyamide-6 thin layer on the surface and analytical pure methanol as the developing agent, and a specific detection probe, and the above detection conditions can separate the F ion and the radionuclide 18 The F ion and the radionuclide 18 The F-labeled FAPI compound is more effectively separated, proving the applicability of the detection method.
[0018] Compared with the prior art, the present application has at least the following advantages:
[0019] The detection method established in the present application can test the radionuclide 18 When detecting the radiochemical purity of the F-labeled FAPI compound, 18 The F ion and the radionuclide 18 The F-labeled FAPI compounds do not affect each other and can be separated, proving that the detection method can realize 18 The F ion and the radionuclide 18 The F-labeled FAPI compound is more effectively separated, 18 The F ion and the radionuclide 18 The F-labeled FAPI compound has good peak shape, proving the applicability of the detection method. BRIEF DESCRIPTION OF DRAWINGS
[0020] In order to more clearly illustrate the specific embodiments of the present application, the drawings required to be used in the specific embodiments or prior art description will be briefly introduced below.
[0021] Figure 1 H 18 TLC detection results of F solution;
[0022] Figure 2 Al 18 TLC detection results of F-NOTA-FAPI-42;
[0023] Figure 3 H 18 F and Al 18 TLC detection results of F-NOTA-FAPI-42 mixed solution;
[0024] Figure 4 H 18 TLC detection results of F solution;
[0025] Figure 5 Al 18 TLC detection results of F-NOTA-FAPI-42;
[0026] Figure 6 H 18 TLC detection results of F solution;
[0027] Figure 7 Al 18 TLC detection results of F-NOTA-FAPI-42;
[0028] Figure 8 H 18 TLC detection results of F solution;
[0029] Figure 9 Al 18 TLC detection results of F-NOTA-FAPI-42;
[0030] Figure 10 H 18 TLC detection results of F solution;
[0031] Figure 11 Al 18 TLC detection results of F-NOTA-FAPI-42;
[0032] Figure 12 H 18 TLC detection results of F solution;
[0033] Figure 13 For Comparative Example 5, Al 18 Figure of TLC method detection result of F-NOTA-FAPI-42. DETAILED DESCRIPTION
[0034] In order to make the objects, technical solutions and advantages of the present application clearer, the technical solutions in the present application will be described clearly and completely below. Obviously, the described embodiments are some of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the protection scope of the present application.
[0035] Unless otherwise specified in the examples, the techniques or conditions are carried out according to the techniques or conditions described in the literature in the art or according to the product instructions. Unless otherwise specified, the instruments and the like used are conventional products that can be purchased through a regular channel. The methods described are conventional methods unless otherwise specified, and the raw materials described can be obtained through public commercial channels unless otherwise specified. Unless otherwise specified in the examples, the techniques or conditions are carried out according to the techniques or conditions described in the literature in the art or according to the product instructions.
[0036] The thin layer chromatography analyzer used in the following examples is bioscan flow-count (radioactive counter) and bioscan mini-scan (scanner), and the specific model is B-MS-1000F. Of course, other thin layer chromatography analyzers used in the art can also be used.
[0037] The detection method used in the following examples of the present application is as follows:
[0038] Thin layer plate: polyamide-6 thin layer plate; sample starting point: 12 mm; developing agent: methanol; developing agent length: 63 mm; test sample: Al 18 F-NOTA-FAPI-42.
[0039] Detection procedure:
[0040] 1) Spotting: radioactive nuclides were taken with a quantitative capillary respectively 18 F-labeled FAPI compound (detection solution) was spotted on a polyamide-6 thin layer plate and dried with cold air or air-dried;
[0041] 2) Development: methanol was used as the developing agent, and the development cylinder was sealed. After development, it was air-dried;
[0042] 3) Detection: radioactive thin layer scanning was used for determination, and radioactive count was obtained. The specific migration value R of the spectrum peak was analyzed. f and radiochemical purity.
[0043] Ratio of the peak R f = a / h, TLC moving speed: 2 mm / sec, t is the peak time, unit: min, a = t*2*60-sample starting point, h = the length of the developing agent.
[0044] Radiochemical purity: main peak area / total peak area.
[0045] Detection results: 18 R of F ion f 0-0.2, radionuclide 18 R of F-labeled FAPI compound f 0.9-1.0.
[0046] System suitability sample forms a single peak or two independent peaks, R f respectively less than or equal to 0.1 (main peak), greater than or equal to 0.9.
[0047] Example 1
[0048] The radionuclide 18 F-labeled FAPI compound provided by the present application:
[0049] 1) Spotting: 5 μL of H 18 F solution was respectively taken by a quantitative capillary, and then was spotted on a polyamide-6 thin layer plate (cut into 1 cm*10 cm) and dried by cold wind or air drying;
[0050] 2) Development: methanol was used as a developing agent, and was placed in a developing jar which was sealed, and was air dried after development;
[0051] 3) Detection: determined by a radio thin layer scanner, TLC moving speed: 2 mm / sec; radioactivity count was obtained, and the ratio of the peak R f and radiochemical purity were analyzed.
[0052] Example 2
[0053] The radionuclide 18 F-labeled FAPI compound provided by the present application:
[0054] 1) Spotting: 5 μL of Al 18 F-NOTA-FAPI-42 was respectively taken by a quantitative capillary, and then was spotted on a polyamide-6 thin layer plate (cut into 1 cm*10 cm) and dried by cold wind or air drying;
[0055] 2) Development: methanol was used as a developing agent, and was placed in a developing jar which was sealed, and was air dried after development;
[0056] 3) Detection: measured by a radio-thin layer scanner, thin layer plate moving speed: 2 mm / sec; radioactive counts were obtained, and the specific migration value R of the spectrum peak was analyzed f and radiochemical purity.
[0057] Example 3
[0058] The radionuclide provided by the application 18 A method for detecting the radiochemical purity of the F-labeled FAPI compound:
[0059] 1) Spotting: 5 μL of H 18 F and Al 18 F-NOTA-FAPI-42 mixed solution was spotted on a polyamide-6 thin layer plate (cut into 1 cm*10 cm) and dried by cold air or air-dried;
[0060] 2) Development: methanol was used as a developing agent, and the developing cylinder was sealed. After development, it was air-dried;
[0061] 3) Detection: measured by a radio-thin layer scanner, thin layer plate moving speed: 2 mm / sec; radioactive counts were obtained, and the specific migration value R of the spectrum peak was analyzed f and radiochemical purity.
[0062] According to the tests of Example 1 and Example 2, the test results under the same conditions are shown in Figure 1 、 Figure 2 and Figure 3 , Figure 1 H 18 F solution 18 F ion) test result graph, Figure 2 Al 18 F-NOTA-FAPI-42 test result graph, Figure 3 H 18 F and Al 18 F-NOTA-FAPI-42 mixed solution test result graph.
[0063] It can be seen from Figure 1 that 18 F ion spectrum peak has a good peak shape and a narrow peak width; from Figure 2 it can be seen that Al 18 F-NOTA-FAPI-42 spectrum peak has a good peak shape and a narrow peak width; from Figure 3 it can be seen that 18 F ion and Al 18 F-NOTA-FAPI-42 spectrum peaks are completely separated and do not affect each other; and 18 R f= a / h = (0.112*2*60-12) / 63 = 0.02, and Al 18 R of F-NOTA-FAPI-42 f = a / h (0.581*2*60-12) / 63 = 0.92, combined Figure 1 、 Figure 2 and Figure 3 It can be seen that the detection method of the present application can be used to test radionuclide 18 F-labeled FAPI compounds, 18 F ions and radionuclides 18 F-labeled FAPI compounds do not affect each other, and can be separated, proving that the detection method can realize 18 F ions and radionuclides 18 F-labeled FAPI compounds are more effectively separated, 18 F ions and radionuclides 18 F-labeled FAPI compounds have good peak shape, proving the applicability of the detection method.
[0064] Comparative Example 1
[0065] The radionuclide provided in the present comparative example 1 18 F-labeled FAPI compound radiochemical purity detection method, which is 18 The detection method of F ion is the same as that of Example 1, and Al 18 The detection method of F-NOTA-FAPI-42 is the same as that of Example 2; the difference is that: the thin layer plate is a silica gel plate, and the developing agent is water; wherein the detection method of the present comparative example is used to detect 18 F ion detection chart as shown in Figure 4 , Al 18 F-NOTA-FAPI-42 detection chart as shown in Figure 5 , from Figure 4 and Figure 5 It can be seen that under the condition of using silica gel plate as thin layer plate and water as developing agent, 18 F ion and Al 18 R of F-NOTA-FAPI-42 f are similar and cannot be separated, and cannot be used for Al 18 F-NOTA-FAPI-42 radiochemical purity detection.
[0066] Comparative Example 2
[0067] The radionuclide provided in the present comparative example 2 18 F-labeled FAPI compound radiochemical purity detection method, which is 18The detection method for F ions is the same as in Example 1, and the detection method for Al is as follows. 18 The detection method for F-NOTA-FAPI-42 is the same as in Example 2; the difference is that a silica gel plate is used for the thin-layer chromatography plate, and acetonitrile is used as the developing solvent; the detection method of this comparative example is used for... 18 The detection graph for F ions is shown below. Figure 6 As shown, for Al 18 The detection results from F-NOTA-FAPI-42 are shown below. Figure 7 As shown; from Figure 6 and Figure 7 It can be seen that, under the conditions of using a silica gel plate as the thin-layer plate and acetonitrile as the developing solvent, 18 F ions and Al 18 F-NOTA-FAPI-42's R f Similar, inseparable, cannot be used in Al 18 F-NOTA-FAPI-42 radiochemical purity detection.
[0068] Comparative Example 3
[0069] The radionuclides provided in this Comparative Example 3 18 A radiochemical purity determination method for F-labeled FAPI compounds, which is effective for... 18 The detection method for F ions is the same as in Example 1, and the detection method for Al is as follows. 18 The detection method for F-NOTA-FAPI-42 is the same as in Example 2; the difference is that a silica gel plate is used for the thin-layer chromatography plate, and methanol is used as the developing solvent; the detection method of this comparative example is used for... 18 The detection graph for F ions is shown below. Figure 8 As shown, for Al 18 The detection results from F-NOTA-FAPI-42 are shown below. Figure 9 As shown; from Figure 8 and Figure 9 It can be seen that, under the conditions of using a silica gel plate as the thin-layer plate and methanol as the developing solvent, 18 F ions and Al 18 F-NOTA-FAPI-42's R f Similar, inseparable, cannot be used in Al 18 F-NOTA-FAPI-42 radiochemical purity detection.
[0070] Comparative Example 4
[0071] The radionuclides provided in Comparative Example 4 18 A radiochemical purity determination method for F-labeled FAPI compounds, which is effective for... 18 The detection method for F ions is the same as in Example 1, and the detection method for Al is as follows. 18The detection method for F-NOTA-FAPI-42 is the same as in Example 2; the difference is that polyamide-6 is used as the thin-layer plate and water is used as the developing agent; the detection method of this comparative example is used to... 18 The detection graph for F ions is shown below. Figure 10 As shown, for Al 18 The detection results from F-NOTA-FAPI-42 are shown below. Figure 11 As shown; from Figure 10 and Figure 11 It can be seen that, under the conditions of using polyamide-6 as the thin-layer plate and water as the developing solvent, 18 F ions and Al 18 F-NOTA-FAPI-42's R f They are close together and cannot be separated; 18 The F ion peak exhibits a tailing effect and has a relatively broad peak width; Al 18 F-NOTA-FAPI-42 exhibits tailing and a relatively broad peak width, therefore polyamide-6 was used as the thin-layer plate; the condition of using water as the developing solvent cannot be used for Al. 18 F-NOTA-FAPI-42 radiochemical purity detection.
[0072] Comparative Example 5
[0073] The radionuclides provided in Comparative Example 5 18 A radiochemical purity determination method for F-labeled FAPI compounds, which is effective for... 18 The detection method for F ions is the same as in Example 1, and the detection method for Al is as follows. 18 The detection method for F-NOTA-FAPI-42 is the same as in Example 2; the difference is that the thin-layer plate used is polyamide-6, and the developing agent is acetonitrile; the detection method of this comparative example is used for... 18 The detection graph for F ions is shown below. Figure 12 As shown, for Al 18 The detection results from F-NOTA-FAPI-42 are shown below. Figure 13 As shown; from Figure 12 and Figure 13 It can be seen that, under the conditions of using polyamide-6 as the thin-layer plate and acetonitrile as the developing solvent, Al 18 F-NOTA-FAPI-42 exhibited tailing and a relatively wide peak width after multiple experiments, with residue at the origin. Therefore, polyamide-6 was used as the thin-layer plate; the conditions using acetonitrile as the developing solvent were not suitable for Al. 18 F-NOTA-FAPI-42 radiochemical purity detection.
[0074] The above examples are only used to illustrate the technical solutions of the present application, but not limit the present application; although the present application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that the technical solutions recorded in the foregoing examples can be modified, or some or all of the technical features can be replaced equivalently; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present application, and they should be covered in the scope of the claims and the specification of the present application.
Claims
1. A radionuclide 18 Method for detecting the radiochemical purity of a F-labelled FAPI compound, characterized in that, comprising detecting the radiochemical purity of a F-labelled FAPI compound using thin layer chromatography on a polyamide-6 thin layer plate with methanol as the developing agent; the radioisotope 18 F-labelled FAPI compound is Al 18 F-labelled FAPI compound is Al 18 F-NOTA-FAPI-42.
2. The radionuclide according to claim 1 18 Method for detecting the radiochemical purity of a F-labelled FAPI compound, characterized in that, It comprises the following steps: 1) Spotting: The radionuclides were pipetted individually using a calibrated capillary 18 F-labeled FAPI compounds were spotted on polyamide-6 thin layer plates and dried with cold air or air-dried; 2) development: using methanol as developing agent, developing the cylinder is closed, after the development is completed, dry; 3) Detection: measured with a radio-thin layer scanner, radioactive counts are taken and the ratio shift value R of the spectrum peaks is analyzed f and radiochemical purity.
3. The radionuclide according to claim 2 18 Method for detecting the radiochemical purity of a F-labelled FAPI compound, characterized in that, The development in step 2) is one development or two developments.
4. The radionuclide according to claim 2 18 Method for detecting the radiochemical purity of a F-labelled FAPI compound, characterized in that, the radionuclide in step 1) 18 The spotting volume of the F-labelled FAPI compound is 2-20 μL.
5. The radionuclide according to claim 2 18 Method for detecting the radiochemical purity of a F-labelled FAPI compound, characterized in that, The methanol is analytical pure methanol, and the polyamide-6 thin layer plate is a plastic thin layer plate with a polyamide-6 thin layer on the surface.
6. The radionuclide according to claim 2 18 Method for detecting the radiochemical purity of a F-labelled FAPI compound, characterized in that, In step 3), a beta-ray detection probe is used.
Citation Information
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