A probe precursor targeting CXCR4 receptor, a probe and its preparation method and application

Abstract

The present invention relates to the field of radioactive drug labeling, and specifically to a probe precursor targeting a CXCR4 receptor, a probe, and a preparation method and application thereof. After the probe precursor targeting a CXCR4 receptor provided by the present invention is combined with a radionuclide, the CXCR4 receptor can be accurately located in the body, and the in vivo targeting performance is excellent. Through nuclear medicine imaging, the purpose of tumor molecular imaging is achieved. The structural formula of the probe precursor targeting a CXCR4 receptor is shown in the following formula (I): Formula (I).

Description

Technical Field

[0001] The present invention relates to the field of radioactive drug labeling, and in particular to a probe precursor targeting a CXCR4 receptor, a probe, and a preparation method and application thereof. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Chemokine receptor 4 (CXCR4) is a structurally conserved G protein-coupled receptor (GPCR) that plays a vital role in the chemokine signaling pathway. Studies have shown that CXCR4 expression levels are significantly increased in more than 30 different types of cancer, including breast cancer, pancreatic cancer, ovarian cancer, lung cancer, prostate cancer, colorectal cancer and skin cancer, as well as hematopoietic malignancies such as leukemia and lymphoma. Therefore, the development of new non-invasive CXCR4 expression monitoring technology is of great significance for promoting early detection of tumors and optimizing tumor treatment strategies.

[0004] With the in-depth development and integration of nuclear medicine and molecular biology, medical imaging technology is moving towards the era of molecular imaging. Among them, positron emission tomography (PET) functional imaging allows people to truly understand and diagnose diseases at the molecular level, especially in the diagnosis and treatment of tumors. By tracing the changes in receptors of diseased tissues and abnormalities in cell signal transduction, it overcomes the defects of modern diagnostic technology, provides a basis for early diagnosis, clinical staging, and efficacy evaluation of tumors, and evaluates prognosis.

[0005] Therefore, developing radiotracers targeting CXCR4 and using positron emission tomography to assess the expression level of CXCR4 in vivo can provide guidance for the diagnosis and treatment of tumors. Summary of the invention

[0006] In order to overcome the above problems, the present invention provides a probe precursor targeting CXCR4 receptor, a probe and a preparation method and application thereof.

[0007] In order to achieve the above technical objectives, the present invention adopts the following technical solutions:

[0008] The first aspect of the present invention provides a probe precursor targeting the CXCR4 receptor, the structural formula of which is shown in the following formula (I):

[0009]

[0010] Formula (I).

[0011] The second aspect of the present invention provides a method for preparing a probe precursor targeting a CXCR4 receptor, comprising:

[0012] Compound 1 is de-Boc protected by using trifluoroacetic acid, and then a chelating agent tetraazacyclododecane tetraacetic acid-succinimidyl ester (DOTA-NHS) and N,N-diisopropylethylamine (DIPEA) are added to carry out a condensation reaction to obtain the probe precursor targeting the CXCR4 receptor;

[0013] The structural formula of compound 1 is as follows:

[0014] .

[0015] The third aspect of the present invention provides a probe targeting CXCR4 receptor, comprising the probe precursor targeting CXCR4 receptor described in the first aspect and / or the probe precursor targeting CXCR4 receptor prepared by the preparation method described in the second aspect and a radionuclide.

[0016] A fourth aspect of the present invention provides a method for preparing the probe according to the third aspect, comprising:

[0017] The radioactive nuclide is mixed with the CXCR4 receptor-targeting probe precursor to react, thereby obtaining the probe.

[0018] The fifth aspect of the present invention provides the use of the probe targeting CXCR4 receptor described in the third aspect and / or the probe targeting CXCR4 receptor prepared by the preparation method described in the fourth aspect in preparing a preparation for detecting the expression level of CXCR4 receptor in tumors.

[0019] The sixth aspect of the present invention provides the use of the probe targeting CXCR4 receptor described in the third aspect and / or the probe targeting CXCR4 receptor prepared by the preparation method described in the fourth aspect in preparing a tracer for PET molecular imaging.

[0020] The seventh aspect of the present invention provides the use of the probe targeting CXCR4 receptor described in the third aspect and / or the probe targeting CXCR4 receptor prepared by the preparation method described in the fourth aspect in preparing a preparation for diagnosing and / or treating CXCR4-overexpressing tumors.

[0021] The beneficial effects of the present invention are:

[0022] (1) After the probe precursor targeting the CXCR4 receptor provided by the present invention is combined with a radionuclide, the CXCR4 receptor can be accurately located in vivo, and the in vivo targeting performance is excellent, and the purpose of tumor molecular imaging can be achieved through nuclear medicine imaging.

[0023] (2) The present invention realizes non-invasive visualization of CXCR4 molecular expression, examines the tumor imaging effect of the probe through small animal PET / CT, and realizes non-invasive diagnosis of tumors, thus having good clinical application prospects.

[0024] (3) The probe targeting the CXCR4 receptor provided by the present invention has the advantages of simple preparation process, low cost, high specificity, high stability in vivo and in vitro, short imaging cycle, and easy clinical transformation. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0026] Figure 1 A synthetic route for the probe precursor targeting the CXCR4 receptor;

[0027] Figure 2 is the high-resolution mass spectrum of compound 1;

[0028] Figure 3 is the H NMR spectrum of compound 1;

[0029] Figure 4 High-resolution mass spectrometry of the probe precursor SDNUM01 targeting the CXCR4 receptor;

[0030] Figure 5 For the probe 68 Ga]Ga-SDNUM01 radiochemical purity test chart;

[0031] Figure 6 For the probe 68 The results of the cellular uptake experiment of Ga]Ga-SDNUM01;

[0032] Figure 7 For the probe 68 Ga]Ga-SDNUM01 cell saturation experimental results;

[0033] Figure 8 For the probe 68 Blood clearance curve of Ga]Ga-SDNUM01;

[0034] Fig. 9 For the probe 68 PET / CT imaging of Ga]Ga-SDNUM01 in tumor-bearing mice;

[0035] Fig.10 Immunohistochemical staining of HT-29 cell tumor sections;

[0036] Fig.11 Immunohistochemical staining of U87MG cell tumor sections;

[0037] Fig.12 For the probe 68 Biodistribution of Ga]Ga-SDNUM01 in vivo. DETAILED DESCRIPTION

[0038] It should be noted that the following detailed descriptions are exemplary and are intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0039] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprising" and / or "including" are used in this specification, it indicates the presence of features, steps, operations, devices, components and / or combinations thereof.

[0040] The first typical embodiment of the present invention provides a probe precursor targeting CXCR4 receptor, the structural formula of which is shown in the following formula (I):

[0041]

[0042] Formula (I).

[0043] The compound represented by formula (I), in addition to the small molecule entity having the above structure, the stereoisomers and physiologically acceptable salts of the compound also belong to the technical solution under the same concept as the first aspect of the present invention, and belong to the technical content of the present invention.

[0044] Among them, physiologically acceptable salts refer to organic salts and inorganic salts of the compounds of the present invention. Physiologically acceptable salts are well known to those skilled in the art. Physiologically acceptable salts include, but are not limited to, inorganic acid salts such as hydrochlorides, hydrobromides, phosphates, sulfates, perchlorates, etc., and organic acid salts such as acetates, oxalates, maleates, tartrates, citrates, succinates, malonates, etc., or salts obtained by other methods described in the literature such as ion exchange methods.

[0045] A second typical embodiment of the present invention provides a method for preparing a probe precursor targeting a CXCR4 receptor, comprising:

[0046] Compound 1 is de-Boc protected by using trifluoroacetic acid, and then a chelating agent tetraazacyclododecane tetraacetic acid-succinimidyl ester (DOTA-NHS) and N,N-diisopropylethylamine (DIPEA) are added to carry out a condensation reaction to obtain the probe precursor targeting the CXCR4 receptor;

[0047] The structural formula of compound 1 is shown below:

[0048] .

[0049] In one or more embodiments, the method of removing Boc protection from compound 1 using trifluoroacetic acid comprises:

[0050] Compound 1 was dissolved in a mixed solution of trifluoroacetic acid and dichloromethane, and after the reaction, the solution was concentrated to remove the trifluoroacetic acid.

[0051] Preferably, in the mixed solution of trifluoroacetic acid and dichloromethane, the volume ratio of trifluoroacetic acid to dichloromethane is 1:(3-5), preferably 1:4.

[0052] In one or more embodiments, the method of adding a chelating agent tetraazacyclododecane tetraacetic acid-succinimide ester (DOTA-NHS) and N,N-diisopropylethylamine (DIPEA) to carry out a condensation reaction comprises:

[0053] Compound 1 is deBoc-protected using trifluoroacetic acid to obtain a deBoc-protected mixture, the deBoc-protected mixture and a chelating agent tetraazacyclododecane tetraacetic acid-succinimide ester are added to an organic solvent, N,N-diisopropylethylamine is added, and the probe precursor targeting the CXCR4 receptor is reacted.

[0054] Preferably, the organic solvent is N,N-dimethylformamide (DMF).

[0055] In one or more embodiments, the molar ratio of the compound 1 to the chelating agent tetraazacyclododecane tetraacetic acid-succinimide ester is 1:(0.9-1.2), preferably 1:1.

[0056] In one or more embodiments, the molar ratio of compound 1 to N,N-diisopropylethylamine is 1:(9-10), preferably 1:9.5.

[0057] A third typical embodiment of the present invention provides a probe targeting CXCR4 receptor, comprising the probe precursor targeting CXCR4 receptor described in the first aspect and / or the probe precursor targeting CXCR4 receptor prepared by the preparation method described in the second aspect and a radionuclide.

[0058] In one or more embodiments, the radionuclide comprises18 F. 94 Tc, 99m Tc, 90 In, 111 In, 67 Ga, 68 Ga, 86 Y. 90 Y. 177 Lu, 151 Tb, 186 Re, 188 Re, 64 Cu, 67 Cu, 55 Co. 57 Co. 43 Sc, 44 Sc, 47 Sc, 225 Ac, 213 Bi, 212 Bi, 212 Pb, 227 Th, 153 Sm, 166 Ho, 152 Gd, 153 Gd, 157 Gd or 166 One of Dy; preferably 68 Ga.

[0059] More preferably, the structural formula of the probe is as shown in formula (II),

[0060]

[0061] Formula (II).

[0062] A fourth typical embodiment of the present invention provides a method for preparing the probe according to the third aspect, comprising:

[0063] After the radioactive nuclide is mixed with the CXCR4 receptor targeting probe precursor for reaction, the CXCR4 receptor targeting probe is obtained.

[0064] A fifth typical embodiment of the present invention provides use of the probe targeting CXCR4 receptor described in the third aspect and / or the probe targeting CXCR4 receptor prepared by the preparation method described in the fourth aspect in preparing a preparation for detecting the expression level of CXCR4 receptor in tumors.

[0065] A sixth typical embodiment of the present invention provides use of the probe targeting CXCR4 receptor described in the third aspect and / or the probe targeting CXCR4 receptor prepared by the preparation method described in the fourth aspect in preparing a tracer for PET molecular imaging.

[0066] A seventh typical embodiment of the present invention provides the use of the probe targeting the CXCR4 receptor described in the third aspect and / or the probe targeting the CXCR4 receptor prepared by the preparation method described in the fourth aspect in the preparation of a preparation for diagnosing and / or treating CXCR4-overexpressing tumors.

[0067] The above tumors include any one of lymphoma, multiple myeloma and solid tumors, such as lung cancer, liver cancer, pancreatic cancer, stomach cancer, colon cancer, thyroid cancer and head and neck tumors, but are not limited thereto.

[0068] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below in conjunction with specific embodiments.

[0069] Figure 1 For the synthetic route of the probe precursor targeting CXCR4 receptor, refer to Figure 1 Synthesis of the CXCR4 receptor-targeting probe precursor SDNUM01.

[0070] Example 1

[0071] 2-Aminopyrimidine (905 mg, 9.5 mmol), tert-butyl 4-bromomethylbenzylcarbamate (1200 mg, 4 mmol) and potassium carbonate (1100 mg, 7.97 mmol) were dissolved in methanol (5 mL), reacted at 65 °C for 2 hours, filtered, concentrated and purified by column chromatography (SiO2) to obtain compound 1 (808 mg, yield 64%).

[0072] The high-resolution mass spectrum of compound 1 is shown in Figure 2 As shown, the H NMR spectrum of compound 1 is as follows Figure 3 shown.

[0073] Compound 1 (20 mg, 0.06 mmol) was dissolved in 2 mL of trifluoroacetic acid (TFA) and dichloromethane (DCM) (volume ratio of 1:4), reacted at room temperature for 30 min, concentrated to remove TFA, and the mixture was dissolved in 1 mL of DMF with DOTA-NHS (30 mg, 0.06 mmol). DIPEA (N,N-diisopropylethylamine) (74.2 mg, 0.57 mmol) was added and reacted at room temperature for 8 h. The mixture was purified by HPLC (reverse phase column, 5% acetonitrile containing 0.1% TFA-95% acetonitrile containing 0.1% TFA, flow rate 3 mL / min) and lyophilized to obtain the probe precursor SDNUM01 targeting the CXCR4 receptor, i.e., the compound shown in formula (I).

[0074] High-resolution mass spectrometry of the probe precursor SDNUM01 targeting the CXCR4 receptor Figure 4 shown.

[0075] Example 2

[0076] The CXCR4 receptor-targeting probe precursor SDNUM01 (4 nmol) was dissolved in 100 μL of NaOAc buffer (0.1 M, pH 4.6), and then 400 μL of 68 GaCl3 solution (2 mCi) was reacted at 95 °C for 20 min to obtain a probe targeting the CXCR4 receptor. 68 Ga]Ga-SDNUM01, that is, the compound represented by formula (II).

[0077] The probe targeting CXCR4 receptor prepared in this example [ 68 The radiochemical purity of Ga]Ga-SDNUM01 was tested by analytical HPLC with a radioactivity detector. The HPLC results are shown in Figure 5 As shown, from Figure 5 It can be seen that the probe [ 68 The radiochemical purity of Ga]Ga-SDNUM01 is greater than 95%.

[0078] Among them, the HPLC mobile phase (A = 0.1% TFA / water, B = 0.1% TFA / acetonitrile), Zorbax 5 μ C18 100 Å (250 × 4.6 mm, 5 μm), and the HPLC elution conditions are shown in Table 1.

[0079] Table 1 HPLC elution conditions

[0080]

[0081] Example 3

[0082] In vitro and in vivo stability studies:

[0083] For in vitro serum stability studies, 10 μL of probe [ 68 Ga]Ga-SDNUM01 was added to 190 μL fetal bovine serum and incubated at 37 °C for 30 or 60 min. After incubation, the samples were added with anhydrous ethanol and centrifuged, filtered, and then tested for radiochemical purity.

[0084] For in vivo stability studies, healthy NSG female mice were used to evaluate the probe [ 68 The metabolic stability of Ga]Ga-SDNUM01 in vivo. Each female mouse was injected with about 37 MBq of probe [ 68 Ga]Ga-SDNUM01, 60 min after injection, blood, liver, and kidney samples were collected from three female mice, and radiochemical purity was tested after processing to observe the radiochemical purity in different samples.

[0085] The results of in vitro and in vivo stability studies are shown in Table 2.

[0086] Table 2 Results of in vitro and in vivo stability studies

[0087]

[0088] From Table 2, it can be seen that the probe [ 68 Ga]Ga-SDNUM01 has good stability in vivo and in vitro and can be used for subsequent experimental studies.

[0089] Example 4

[0090] Hydrophilicity and lipophilicity determination:

[0091] 10 μL probe[ 68 Ga]Ga-SDNUM01 was diluted to 500 μL with HEPES buffer at pH = 7.4, and then 500 μL of n-octanol was added and shaken vigorously. 100 μL of liquid was taken from each of the aqueous and organic phases to measure their radioactivity counts. The lipid-water partition coefficient was calculated using the formula [Log (radioactivity counts in the organic phase / radioactivity counts in the aqueous phase)], and the probe [ 68 The log D of Ga]Ga-SDNUM01 is -3.25±0.13. The experimental results show that the probe [ 68 Ga]Ga-SDNUM01 has high hydrophilicity.

[0092] Example 5

[0093] Cellular uptake and saturation experimental studies:

[0094] 5.1 Cell uptake experiment: For the cell uptake experiment, HT-29 cells were cultured at 3×10 5 Cells were seeded at a density of 100 cells / well in 24-well plates and incubated at 37°C with the probe [ 68 Ga]Ga-SDNUM01 (100 nM) was co-incubated for 15, 30, 60, and 120 min. To evaluate the specificity of uptake, a blocking experiment was performed using a 1000-fold molar concentration of the CXCR4-targeted inhibitor T140. After incubation, the cells were washed three times with PBS, lysed with 1 M NaOH solution, and the radioactivity of the cell suspension was quantified using a γ counter. Figure 6 As shown, the probe [ 68 The cellular uptake of Ga]Ga-SDNUM01 increased over time and gradually plateaued after 60 min. In contrast, in the presence of the CXCR4-targeting inhibitor T140, the probe [ 68 Ga]Ga-SDNUM01 uptake was significantly reduced, indicating that the probe [68 Ga]Ga-SDNUM01 binds specifically to the CXCR4 receptor.

[0095] 5.2 Cell saturation experiment: To evaluate the probe [ 68 The binding affinity of Ga]Ga-SDNUM01 to CXCR4 receptor was determined using HT-29 cell line, and the equilibrium dissociation constant (K d For cell saturation experiments, HT-29 cells were plated at 3 × 10 5 Cells were seeded at a density of 100 μg / well in 24-well plates and incubated with different concentrations of probes [ 68 Ga]Ga-SDNUM01 (0.78125 nM, 1.5625 nM, 3.125 nM, 6.25 nM, 12.5 nM, 25 nM, 50 nM, and 100 nM) was incubated for 1 h. In parallel, nonspecific binding was assessed by co-incubating cells with 1000-fold molar concentrations of the CXCR4-targeted inhibitor T140 over the same concentration range. After incubation, the radioactivity of the cell suspension was measured using a gamma counter, and the data were analyzed by nonlinear regression using GraphPad Prism 5.0 to determine K d Value. Figure 7 As shown, the results of the cell saturation experiment showed that the probe [ 68 Ga]Ga-SDNUM01 has a high binding affinity with CXCR4 receptors. 68 Ga]Ga-SDNUM01 K d The value was 36.69±1.89 nM. When incubated with the CXCR4 targeted inhibitor T140 solution, the probe [ 68 The binding of Ga]Ga-SDNUM01 to the CXCR4 receptor was significantly blocked, indicating that its binding to the CXCR4 receptor was specific.

[0096] Example 6

[0097] Pharmacokinetic properties studies

[0098] Eight-week-old female BALB / c mice were injected with the probe via the tail vein. 68 Ga]Ga-SDNUM01 (0.2 mL, 7.4 MBq) was injected, and blood samples were collected from the tail vein at 1, 3, 5, 10, 15, 30, 45, 60, and 90 minutes after injection. The samples were weighed and their radioactivity was measured using a γ counter. The pharmacokinetic curve was characterized using DAS software. The results are shown in Figure 8As shown. The drug concentration changes obtained by DAS software fitting reflect the summary of the distribution phase (α phase) and the elimination phase (β phase). The blood drug concentration in the distribution phase (α phase) drops rapidly after administration, which is the fast elimination phase. The drug concentration in the elimination phase (β phase) decreases proportionally according to the dynamic equilibrium law, which is the slow elimination phase. The probe [ 68 The blood clearance curve of Ga]Ga-SDNUM01 conformed to the two-compartment model, with the distribution phase half-life (T1 / 2α) of 1.31±0.11 minutes and the elimination phase half-life (T1 / 2β) of 30.61±3.31 minutes, indicating a moderate blood metabolism time.

[0099] Example 7

[0100] Small Animal PET / CT Imaging:

[0101] Under anesthesia with 2% isoflurane in oxygen, a Mediso NanoScan μ-PET / CT scanner was used to scan the injected probe [ 68 PET / CT imaging was performed 15 and 45 minutes after the administration of Ga]Ga-SDNUM01 (0.2 mL, 7.4 MBq). HT-29 tumor-bearing mice were randomly divided into an experimental group and a blocking group (n = 3). In the blocking group, the mice were simultaneously injected with the probe [ 68 Ga]Ga-SDNUM01 and CXCR4 targeted inhibitor T140 (20 mg / kg). In the negative control group, U87MG tumor-bearing mice with low CXCR4 expression were used for PET / CT imaging at the same time point. PET / CT images were reconstructed using Nucline NanoScan 3.00 software and subsequently analyzed using InterView FUSION 3.0 software. Fig. 9 As shown, the probe [ 68 Ga]Ga-SDNUM01 showed excellent imaging effect at 15 minutes (SUV: 0.86±0.03), but due to its short tumor retention time, tumor uptake was low at 45 minutes (SUV: 0.31±0.01). In the blocking group and negative control group, tumor uptake was significantly reduced, suggesting that the probe [ 68 Ga]Ga-SDNUM01 has a high specificity for CXCR4 receptor uptake, so 15 minutes was determined to be the optimal imaging time point.

[0102] Example 8

[0103] Immunohistochemical staining:

[0104] HT29 cell and U87MG cell tumor-bearing mice were killed, their tumor tissues were isolated and tumor sections were prepared. The samples were fixed in 10% formalin, embedded in paraffin, cut into 5 μm thick sections and mounted on slides. The sections of the experimental group were incubated with rabbit anti-human CXCR4 antibody and then analyzed by immunohistochemical staining. The results are shown in the figure, where Fig.10 This is a HT-29 cell tumor section. Fig.11 This is a U87MG cell tumor section. The experimental results show that HT29 tumors are immunoreactive while U87MG is not.

[0105] Example 9

[0106] Biodistribution studies:

[0107] In the biodistribution study, the probe was injected into the tail vein of HT-29 tumor-bearing mice. 68 Ga]Ga-SDNUM01 (0.1 mL, 3.7 MBq). Tumor-bearing mice were killed 15 minutes or 45 minutes after injection, and tumors, blood, and a series of major tissues and organs (including heart, lung, liver, kidney, spleen, intestine, bone, and muscle) were collected. Each tissue and organ sample was weighed, and the radioactivity of each tissue and organ sample was measured using a γ counter. Fig.12 As shown, the biodistribution results were basically consistent with the PET imaging results. At 15 minutes, the probe [ 68 Ga]Ga-SDNUM01 showed high tumor uptake and a favorable tumor-to-liver ratio.

[0108] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A probe precursor targeting CXCR4 receptor, characterized in that: Its structural formula is shown in the following formula (I): Formula (I).

2. The method for preparing a probe precursor targeting CXCR4 receptor according to claim 1, characterized in that: include: Using trifluoroacetic acid to remove the Boc protection of compound 1, and then adding a chelating agent tetraazacyclododecane tetraacetic acid-succinimide ester and N,N-diisopropylethylamine to carry out a condensation reaction to obtain the probe precursor targeting the CXCR4 receptor; The structural formula of compound 1 is as follows: 。 3. The preparation method according to claim 2, characterized in that: The method of removing Boc protection from compound 1 using trifluoroacetic acid includes: Dissolve compound 1 in a mixed solution of trifluoroacetic acid and dichloromethane, and concentrate to remove trifluoroacetic acid after the reaction; The method of adding a chelating agent tetraazacyclododecane tetraacetic acid-succinimide ester and N,N-diisopropylethylamine to carry out a condensation reaction comprises: Compound 1 is deBoc-protected using trifluoroacetic acid to obtain a deBoc-protected mixture, the deBoc-protected mixture and a chelating agent tetraazacyclododecane tetraacetic acid-succinimide ester are added to an organic solvent, N,N-diisopropylethylamine is added, and the probe precursor targeting the CXCR4 receptor is reacted.

4. A probe targeting CXCR4 receptor, characterized in that: The method comprises the CXCR4 receptor targeting probe precursor according to claim 1 or the CXCR4 receptor targeting probe precursor prepared by the preparation method according to claim 2 and a radioactive nuclide; The radionuclide is selected from 111 In, 67 Ga, 68 Ga, 86 Y. 90 Y. 177 Lu, 64 Cu, 67 Cu, 55 Co. 57 Co. 43 Sc, 44 Sc, 47 Sc, 225 Ac, 213 Bi, 212 Bi, 212 Pb, 153 Sm, 166 Ho, 153 Gd and 157 One of Gd.

5. The probe targeting CXCR4 receptor according to claim 4, characterized in that: The structural formula of the probe targeting the CXCR4 receptor is shown in formula (II). Formula (II).

6. The method for preparing the probe targeting the CXCR4 receptor according to claim 4 or 5, comprising: After the radioactive nuclide is mixed with the CXCR4 receptor targeting probe precursor for reaction, the CXCR4 receptor targeting probe is obtained.

7. Use of the probe targeting CXCR4 receptor according to claim 4 or 5 or the probe targeting CXCR4 receptor prepared by the preparation method according to claim 6 in preparing a preparation for detecting the expression level of CXCR4 receptor in tumors.

8. Use of the probe targeting CXCR4 receptor according to claim 4 or 5 or the probe targeting CXCR4 receptor prepared by the preparation method according to claim 6 in preparing a tracer for PET molecular imaging.

9. Use of the probe targeting CXCR4 receptor according to claim 4 or 5 or the probe targeting CXCR4 receptor prepared by the preparation method according to claim 6 in preparing a preparation for diagnosing tumors with high CXCR4 expression.

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