A compound targeting the DDR1 receptor and its derived radiotracer

Abstract

The present invention relates to the technical field of radioactive drug labeling, and particularly relates to a compound targeting the DDR1 receptor and a radioactive tracer derived therefrom. The radioactive tracer formed by mixing the compound targeting the DDR1 receptor with a radionuclide has a strong receptor binding force with the DDR1 receptor, can accurately locate the DDR1 receptor in vivo, has excellent in vivo targeting performance, and realizes the purpose of tumor molecular imaging through nuclear medicine imaging. The compound targeting the DDR1 receptor has the following structural formula shown in formula (I): Formula (I).

Description

Technical Field

[0001] The present invention relates to the technical field of radioactive drug labeling, and particularly relates to a compound targeting the DDR1 receptor and a radioactive tracer derived therefrom. Background Art

[0002] Disclosing the information of this background art section is only intended to enhance the overall understanding of the present invention, and it is not necessarily regarded as an admission or an implication in any form that this information constitutes the prior art already known to those of ordinary skill in the art.

[0003] Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase that plays a key role in regulating important processes such as cell differentiation, proliferation, adhesion, migration, invasion, and matrix remodeling. Research has confirmed that DDR1 is expressed in a variety of tumors, such as lung cancer, breast cancer, colorectal cancer, ovarian cancer, esophageal cancer, head and neck tumors, liver cancer, and testicular cancer, and its high expression is closely related to poor tumor prognosis. Given the link between changes in DDR1 function and tumor development, DDR1 has become a new target for cancer research. Therefore, developing a new non-invasive DDR1 expression monitoring technology is of great significance for promoting early tumor detection and optimizing tumor treatment strategies.

[0004] With the in-depth development and integration of nuclear medicine and molecular biology, medical imaging technology has entered the era of molecular imaging. Among them, functional imaging by positron emission tomography (PET) enables people to truly understand and diagnose diseases at the molecular level, especially showing advantages in the diagnosis and treatment of tumors. By tracing receptor changes and abnormal cell signal transduction in diseased tissues, it can overcome the defects in modern diagnostic technologies, provide a basis for early tumor diagnosis, clinical staging, and efficacy evaluation, and evaluate the prognosis.

[0005] Therefore, developing a radioactive tracer targeting the DDR1 receptor and using positron emission tomography to evaluate the expression level of the DDR1 receptor in vivo can provide guidance for tumor diagnosis and treatment. Summary of the Invention

[0006] In order to overcome the above problems, the present invention provides a compound targeting the DDR1 receptor and a radioactive tracer derived therefrom.

[0007] To achieve the above technical objectives, the present invention adopts the following technical solutions:

[0008] In the first aspect of the present invention, a compound targeting the DDR1 receptor is provided, and its structural formula is shown as the following formula (Ⅰ):

[0009]

[0010] Formula (I).

[0011] In the second aspect of the present invention, there is provided an intermediate of the compound targeting the DDR1 receptor described in the first aspect, and its structural formula is shown as the following formula (II):

[0012]

[0013] Formula (II).

[0014] In the third aspect of the present invention, there is provided a preparation method of the compound targeting the DDR1 receptor described in the first aspect, including the following steps:

[0015] Deprotect the compound shown in formula (II) from Boc, and then add the chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-N-hydroxysuccinimide ester (DOTA-NHS) and N,N-diisopropylethylamine (DIPEA) for condensation reaction to obtain the compound targeting the DDR1 receptor.

[0016] In the fourth aspect of the present invention, there is provided a radioactive tracer, including the compound targeting the DDR1 receptor described in the first aspect or the compound targeting the DDR1 receptor prepared by the preparation method described in the third aspect and a radionuclide.

[0017] In the fifth aspect of the present invention, there is provided a preparation method of the radioactive tracer described in the fourth aspect, including:

[0018] Mix and react the radionuclide with the compound targeting the DDR1 receptor to obtain a radioactive tracer.

[0019] In the sixth aspect of the present invention, there is provided an application of the radioactive tracer described in the fourth aspect or the radioactive tracer prepared by the preparation method described in the fifth aspect in the preparation of a preparation for detecting the expression level of DDR1 receptor in tumors.

[0020] In the seventh aspect of the present invention, there is provided an application of the radioactive tracer described in the fourth aspect or the radioactive tracer prepared by the preparation method described in the fifth aspect in the preparation of a preparation for diagnosing tumors with high expression of DDR1 receptor.

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

[0022] (1) The radioactive tracer provided by the present invention has a strong receptor binding force with the DDR1 receptor, can accurately locate the DDR1 receptor in vivo, has excellent in vivo targeting performance, and realizes the purpose of tumor molecular imaging through nuclear medicine imaging.

[0023] (2) The present invention realizes the non-invasive visualization of the expression of DDR1 receptor molecules. By investigating the tumor imaging effect of radioactive tracers through small animal PET / CT, the non-invasive diagnosis of tumors is achieved, so it has good clinical application prospects.

[0024] (3) The compounds targeting DDR1 receptors and the derived radioactive tracers provided by the present invention have the advantages of simple preparation process, low cost, high specificity, high stability in vivo and in vitro, long imaging cycle, and easy clinical transformation. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The accompanying drawings forming a part of the present invention are used to provide a further understanding of the present invention. The schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention.

[0026] Figure 1 It is the synthesis route of the compound SDUHYX01 targeting DDR1 receptor shown in formula (I);

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

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

[0029] Figure 4 It is the high-resolution mass spectrum of the compound shown in formula (II);

[0030] Figure 5 It is the high-resolution mass spectrum of the compound SDUHYX01 targeting DDR1 receptor;

[0031] Figure 6 It is for the radiochemical purity detection chart of the radioactive tracer 68 [68Ga]Ga-SDUHYX01;

[0032] Figure 7 It is for the cell uptake and internalization experimental results of the radioactive tracer 68 [68Ga]Ga-SDUHYX01;

[0033] Figure 8 It is for the cell saturation experimental results of the radioactive tracer 68 [68Ga]Ga-SDUHYX01;

[0034] Figure 9 It is for the blood clearance curve of the radioactive tracer 68 [68Ga]Ga-SDUHYX01;

[0035] Figure 10 It is for the radioactive tracer 68PET / CT imaging of Ga]Ga-SDUHYX01 in tumor-bearing mice;

[0036] Figure 11 as a radioactive tracer 68 In vivo biodistribution map of Ga]Ga-SDUHYX01. Specific implementation manners

[0037] It should be noted that the following detailed description is exemplary and is intended to provide further illustration of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those of ordinary skill in the technical field to which the present invention belongs.

[0038] It should be noted that the terms used herein are only for describing specific implementation manners and are not intended to limit the 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, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0039] The first typical implementation manner of the present invention provides a compound targeting the DDR1 receptor, and its structural formula is shown as the following formula (I):

[0040]

[0041] Formula (I).

[0042] For the compound shown in formula (I), in addition to the small molecule entity with the above structure, the physiologically acceptable salts of the compound also belong to the technical solutions under the same concept of the first aspect of the present invention and are the technical contents protected by the present invention application.

[0043] Among them, the physiologically acceptable salts refer to the 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 hydrochloride, hydrobromide, phosphate, sulfate, perchlorate, etc., and organic acid salts such as acetate, oxalate, maleate, tartrate, citrate, succinate, malonate, etc., or salts obtained by other methods such as ion exchange method recorded in the literature.

[0044] The second typical implementation manner of the present invention provides an intermediate of the compound targeting the DDR1 receptor described in the first aspect, and its structural formula is shown as the following formula (II):

[0045]

[0046] Formula (II).

[0047] The third typical embodiment of the present invention provides a method for preparing a compound targeting the DDR1 receptor described in the first aspect, comprising the following steps:

[0048] Remove the Boc protection from the compound shown in formula (II), and then add the chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-N-hydroxysuccinimide ester (DOTA-NHS) and N,N-diisopropylethylamine (DIPEA) for condensation reaction to obtain the compound targeting the DDR1 receptor.

[0049] In one or more embodiments, the method for removing the Boc protection from the compound shown in formula (II) includes:

[0050] Dissolve the compound shown in formula (II) in a mixed solution of trifluoroacetic acid and dichloromethane, and after the reaction, concentrate to remove 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 for adding the chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-N-hydroxysuccinimide ester (DOTA-NHS) and N,N-diisopropylethylamine (DIPEA) for condensation reaction includes:

[0053] Remove the Boc protection from the compound shown in formula (II) to obtain a Boc-deprotected mixture, add the Boc-deprotected mixture and the chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-N-hydroxysuccinimide ester to an organic solvent, add N,N-diisopropylethylamine, and react to obtain the compound targeting the DDR1 receptor.

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

[0055] In one or more embodiments, the molar ratio of the compound shown in formula (II) to the chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-N-hydroxysuccinimide ester is 1:(0.9 - 1.2), preferably 1:1.

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

[0057] The fourth typical embodiment of the present invention provides a radioactive tracer, comprising the compound targeting the DDR1 receptor described in the first aspect or the compound targeting the DDR1 receptor prepared by the preparation method described in the third aspect and a radionuclide.

[0058] In one or more embodiments, the radionuclide is selected from18 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 and 166 one of Dy; preferably 68 Ga.

[0059] Preferably, the structural formula of the radioactive tracer is as shown in the following formula (III):

[0060]

[0061] Formula (III).

[0062] The fifth typical embodiment of the present invention provides a preparation method of the radioactive tracer described in the fourth aspect, including:

[0063] Mixing and reacting the radionuclide with the compound targeting the DDR1 receptor to obtain a radioactive tracer.

[0064] The sixth typical embodiment of the present invention provides the application of the radioactive tracer described in the fourth aspect or the radioactive tracer prepared by the preparation method described in the fifth aspect in the preparation of a preparation for detecting the expression level of the DDR1 receptor in tumors.

[0065] The seventh typical embodiment of the present invention provides the application of the radioactive tracer described in the fourth aspect or the radioactive tracer prepared by the preparation method described in the fifth aspect in the preparation of a preparation for diagnosing tumors with high expression of the DDR1 receptor.

[0066] The above-mentioned tumors include any one of lymphoma, multiple myeloma, and solid tumors. For example, but not limited to, lung cancer, liver cancer, pancreatic cancer, gastric cancer, colon cancer, thyroid cancer, and head and neck tumors, etc.

[0067] 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.

[0068] In the present invention, the DDR1 receptor highly expressed tumor model selects the HT-29 cell colon cancer model.

[0069] Example 1

[0070] Figure 1 The synthetic route of the compound SDUHYX01 targeting the DDR1 receptor shown in formula (I) is as follows. Refer to Figure 1 to synthesize the compound SDUHYX01 targeting the DDR1 receptor.

[0071] Dissolve 1-(bromomethyl)-3-nitro-5-(trifluoromethyl)benzene (1415 mg, 5 mmol), N-Boc-ethylenediamine (1200 mg, 7.5 mmol), and potassium carbonate (1035 mg, 7.5 mmol) in DMF (5 mL), react at 25 °C for 12 hours, filter by suction, and after concentration, purify by column chromatography (SiO2) to obtain compound 1 (1633.5 mg, yield 90%). The high-resolution mass spectrum of compound 1 is as shown in Figure 2 and the 1H NMR spectrum of compound 1 is as shown in Figure 3 shown.

[0072] Dissolve compound 1 (1633.5 mg, 4.5 mmol) in 5 mL of methanol, add Pd / C (the loading rate of Pd is 10%, 490 mg), react under a hydrogen atmosphere for 16 hours, filter, and then dissolve the product and 3-(2-pyrazolo[1,5-a]pyrimidin-6-yl ethynyl)benzoic acid (1385 mg, 5 mmol) in 5 mL of DMF, add 2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU) (2578 mg, 6.75 mmol), DIPEA (1451 mg, 11.25 mmol), and react at room temperature overnight to obtain the compound shown in formula (II) (1705 mg, yield 64%). The high-resolution mass spectrum of the compound shown in formula (II) is as shown in Figure 4 shown.

[0073] Dissolve the compound shown in formula (II) (35.5 mg, 0.06 mmol) in 2 mL of trifluoroacetic acid (TFA) and dichloromethane (DCM) (volume ratio 1:4), react at room temperature for 30 min, concentrate to remove TFA. Dissolve the de-Boc protected mixture and DOTA-NHS (30 mg, 0.06 mmol) in 1 mL of DMF, add DIPEA (74.2 mg, 0.57 mmol), react at room temperature for 10 h, purify by HPLC (reverse-phase chromatographic column, 5% acetonitrile containing 0.1% TFA, 95% acetonitrile containing 0.1% TFA, flow rate 3 mL / min), and lyophilize to obtain the compound SDUHYX01 targeting the DDR1 receptor (28.5 mg, yield 54%), which is the compound shown in formula (I). The high-resolution mass spectrometry results of the compound SDUHYX01 targeting the DDR1 receptor are shown in Figure 5.

[0074] Example 2

[0075] Dissolve the compound SDUHYX01 targeting the DDR1 receptor (4 nmol) in 100 μL of NaOAc buffer solution (concentration 0.1 M, pH 4.6), and then add 400 μL of 68 GaCl3 solution (2 mCi), react at 95 °C for 15 min to obtain the radioactive tracer 68 Ga]Ga-SDUHYX01.

[0076] For the radioactive tracer 68 Ga]Ga-SDUHYX01 prepared in this example, perform radiochemical purity detection by analytical HPLC with a radioactive detector. The HPLC results are as shown in Figure 6 It can be seen from Figure 6 that the radiochemical purity of the radioactive tracer 68 Ga]Ga-SDUHYX01 is greater than 95%.

[0077] 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.

[0078] Table 1 HPLC elution conditions

[0079]

[0080] Example 3

[0081] In vitro and in vivo stability studies:

[0082] For in vitro serum stability study: 10 μL of the radioactive tracer 68 Ga]Ga-SDUHYX01 was added to 190 μL of fetal bovine serum and incubated at 37 °C for 30 or 60 min. After incubation, absolute ethanol was added to the sample, followed by centrifugation and filtration, and then radiochemical purity detection was performed.

[0083] For in vivo stability study: Healthy NSG female mice were used to evaluate the metabolic stability of the radioactive tracer 68 Ga]Ga-SDUHYX01 in vivo. Each female mouse was injected with approximately 37 MBq of the radioactive tracer 68 Ga]Ga-SDUHYX01 via the tail vein. At 60 min after injection, blood, liver, and kidney samples were collected from 3 female mice respectively, and after processing, radiochemical purity detection was performed to observe the radiochemical purity in different samples.

[0084] The results of in vitro and in vivo stability studies are shown in Table 2.

[0085] Table 2 Results of in vitro and in vivo stability studies

[0086]

[0087] As can be seen from Table 2, the radioactive tracer 68 Ga]Ga-SDUHYX01 has good in vitro and in vivo stability and can be used for subsequent experimental studies.

[0088] Example 4

[0089] Hydrophilic-lipophilic property determination:

[0090] 10 μL of the radioactive tracer 68 Ga]Ga-SDUHYX01 was diluted to 500 μL with HEPES buffer solution 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 phase and the organic phase to measure its radioactivity count. The partition coefficient of lipid / water was calculated by the formula [Log (radioactivity count in the organic phase / radioactivity count in the aqueous phase)]. The log D of the radioactive tracer 68 Ga]Ga-SDUHYX01 was -1.25 ± 0.02. The experimental results showed that the radioactive tracer 68 Ga]Ga-SDUHYX01 had certain hydrophilicity.

[0091] Example 5

[0092] Cell uptake, internalization and saturation experimental study:

[0093] (1) Cell uptake and internalization experiment: For the cell uptake and internalization experiment, HT-29 cells were seeded at a density of 5×105 The cells were seeded at a density of [cell number] / well in 12-well plates and co-incubated with the radioactive tracer 68 Ga]Ga-SDUHYX01 (100 nM) at 37 °C for 30, 60, and 120 minutes. To evaluate the specificity of uptake, a blocking experiment was performed using a 1000-fold molar excess of the DDR1-targeting inhibitor 7rh. After incubation, the cells were washed three times with PBS, acidified with 0.05 M glycine buffer (pH = 2.8) for 10 minutes, washed three times with PBS, all the liquid was collected, lysed with 1 M NaOH solution, and then the radioactivity of the collected liquid and cell suspension was quantified using a gamma counter. The results are shown in Figure 7 and indicate that Figure 7 the cellular uptake of the radioactive tracer 68 Ga]Ga-SDUHYX01 increased over time and had a high internalization efficiency. In contrast, the uptake of the radioactive tracer 68 Ga]Ga-SDUHYX01 was significantly reduced in the presence of the DDR1-targeting inhibitor 7rh, indicating that the binding of the radioactive tracer 68 Ga]Ga-SDUHYX01 to the DDR1 receptor was specific.

[0094] The structure of the DDR1-targeting inhibitor 7rh is shown below:

[0095] .

[0096] (2) Cell saturation experiment: To evaluate the binding affinity of the radioactive tracer 68 Ga]Ga-SDUHYX01 to the DDR1 receptor, the equilibrium dissociation constant (K d d) was determined using the HT-29 cell line. For the cell saturation experiment, HT-29 cells were seeded at a density of 3×10 5 cells / well in 24-well plates and incubated for 1 hour with different concentrations of the radioactive tracer 68 Ga]Ga-SDHYX01 (0.78125 nM, 1.5625 nM, 3.125 nM, 6.25 nM, 12.5 nM, 25 nM, 50 nM, and 100 nM). Meanwhile, the non-specific binding was evaluated by co-incubating the cells with a 1000-fold molar excess of the DDR1-targeting inhibitor 7rh in the same concentration range. After incubation, the radioactivity of the cell suspension was measured using a gamma counter, and the data were analyzed by non-linear regression using GraphPad Prism 5.0 to determine the K d d value. The results are shown in Figure 8 and indicate that Figure 8 the radioactive tracer68 Ga]Ga-SDUHYX01 has a high binding affinity for the DDR1 receptor, and the radiotracer 68 Ga]Ga-SDUHYX01 has a K d value of 61.81 ± 0.43 nM. When incubated with the 7rh solution, the binding of the radiotracer 68 Ga]Ga-SDUHYX01 to the DDR1 receptor was significantly blocked, indicating its specific binding to the DDR1 receptor.

[0097] Example 6

[0098] Pharmacokinetic property study

[0099] The radiotracer 68 Ga]Ga-SDUHYX01 (0.2 mL, 7.4 MBq) was injected into 8-week-old female BALB / c mice via the tail vein, and blood samples were collected from the tail vein at 1, 3, 5, 10, 15, 30, 60, 90, and 120 minutes after injection. The samples were weighed and their radioactivity was measured using a gamma counter. The pharmacokinetic curve was characterized using DAS software. The results are as Figure 9 shown. The change in drug concentration obtained by fitting with DAS software reflects the summary of the distribution phase (α phase) and the elimination phase (β phase). In the distribution phase (α phase), the blood drug concentration decreased rapidly after administration, which is the fast elimination stage. The drug concentration in the elimination phase (β phase) decreased proportionally following the law of dynamic equilibrium, which is the slow elimination stage. By analyzing with DAS software, the blood clearance curve of the radiotracer 68 Ga]Ga-SDUHYX01 conforms to a two-compartment model, with a distribution-phase half-life (T1 / 2α) of 0.93 ± 0.11 minutes and an elimination-phase half-life (T1 / 2β) of 53.07 ± 2.26 minutes, and the blood metabolism time is moderate.

[0100] Example 8

[0101] Small animal PET / CT imaging:

[0102] Under anesthesia with 2% isoflurane in oxygen, PET / CT imaging was performed using a Mediso NanoScan μ-PET / CT scanner at 30 and 60 minutes after injection of the radiotracer 68 Ga]Ga-SDUHYX01 (0.2 mL, 7.4 MBq). HT-29 tumor-bearing mice (with tumors subcutaneously implanted in the shoulder) were randomly divided into an experimental group and a blocking group (n = 3). In the blocking group, the radiotracer 68Ga]Ga-SDUHYX01 and DDR1-targeted inhibitor 7rh (20 mg / kg). PET / CT images were reconstructed using Nucline NanoScan 3.00 software and then analyzed using InterView FUSION 3.0 software. As Figure 10 shown, the radiotracer 68 Ga]Ga-SDUHYX01 showed excellent imaging performance at 60 minutes (SUV: 0.56 ± 0.03), but due to its relatively high lipophilicity, the tumor background was relatively low at 30 minutes. While in the blocking group, the tumor uptake was significantly reduced, indicating that the radiotracer 68 Ga]Ga-SDUHYX01 has high specificity for DDR1 receptor uptake.

[0103] Example 9

[0104] Biodistribution study:

[0105] In the biodistribution study, HT-29 tumor-bearing mice (subcutaneous tumor in the shoulder) were injected with the radiotracer 68 Ga]Ga-SDUHYX01 (0.1 mL, 3.7 MBq) via the tail vein. The tumor-bearing mice were sacrificed at 30 minutes or 60 minutes after injection, and the tumors, blood, and a series of major tissues and organs (including the heart, lungs, liver, kidneys, spleen, intestines, bones, and muscles) were collected. The samples of each tissue and organ were weighed, and the radioactivity of each tissue and organ sample was measured using a gamma counter. As Figure 11 shown, the biodistribution results were basically consistent with the PET imaging results. At 60 minutes, the radiotracer 68 Ga]Ga-SDUHYX01 showed relatively high tumor uptake and a good tumor-to-background ratio. However, due to its relatively high lipophilicity, the tumor-to-liver ratio (the ratio of the radioactivity taken up by the tumor to the radioactivity taken up by the liver) was relatively low at 30 minutes.

[0106] The above are only the preferred embodiments of the present invention and are not used to limit the present invention. For those skilled in the art, the present invention can have various changes and modifications. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A compound targeting DDR1 receptor, characterized in that: Its structural formula is shown in the following formula (I): Formula (I).

2. The intermediate of the compound targeting DDR1 receptor according to claim 1, characterized in that: Its structural formula is shown in the following formula (II): Formula (II).

3. The method for preparing the compound targeting DDR1 receptor according to claim 1, characterized in that: The steps include: The compound represented by formula (II) is deprotected from Boc, and then a chelating agent tetraazacyclododecane tetraacetic acid-succinimide ester and N,N-diisopropylethylamine are added to carry out a condensation reaction to obtain a compound targeting the DDR1 receptor; Formula (II).

4. The preparation method according to claim 3, characterized in that: The method for removing Boc protection from the compound represented by formula (II) comprises: The compound represented by formula (II) is dissolved in a mixed solution of trifluoroacetic acid and dichloromethane, and after the reaction, the solution is concentrated to remove the trifluoroacetic acid; The method of adding a chelating agent tetraazacyclododecane tetraacetic acid-succinimide ester and N,N-diisopropylethylamine to carry out a condensation reaction comprises: The compound represented by formula (II) is de-Boc protected to obtain a de-Boc protected mixture, the de-Boc protected mixture and the chelating agent tetraazacyclododecane tetraacetic acid-succinimide ester are added to an organic solvent, and N,N-diisopropylethylamine is added to react to obtain the compound targeting the DDR1 receptor.

5. A radioactive tracer, characterized in that A compound targeting DDR1 receptor according to claim 1 or a compound targeting DDR1 receptor prepared by the preparation method according to claim 3 and a radionuclide; 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.

6. The radioactive tracer according to claim 5, characterized in that The structural formula of the radioactive tracer is shown in the following formula (III): Formula (III).

7. The method for preparing a radioactive tracer according to claim 5, characterized in that: include: After the radioactive nuclide is mixed and reacted with the compound targeting DDR1 receptor, a radioactive tracer is obtained.

8. Use of the radioactive tracer according to claim 5 or the radioactive tracer prepared by the preparation method according to claim 7 in preparing a preparation for detecting the expression level of DDR1 receptor in tumors.

9. Use of the radioactive tracer according to claim 5 or the radioactive tracer prepared by the preparation method according to claim 7 in preparing a preparation for diagnosing tumors with high expression of DDR1 receptor.

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