Compound targeting DDR1 receptor and radioactive tracer agent derived from compound

Abstract

The invention relates to the technical field of radiopharmaceutical labeling, in particular to a compound targeting a DDR1 receptor and a radioactive tracer derived from the compound. According to the present invention, the radioactive tracer agent generated after the mixing reaction of the DDR1 receptor targeting compound and the radionuclide has strong receptor binding force with the DDR1 receptor, can accurately position the DDR1 receptor in vivo, has excellent in-vivo targeting performance, and can achieve the tumor molecular imaging purpose through nuclear medicine imaging. The invention relates to a DDR1 receptor targeting compound, which has a structural formula as shown in a formula (I): # imgabs0 # formula (I).

Description

Technical Field

[0001] The invention relates to the technical field of radioactive drug labeling, and in particular to a compound targeting DDR1 receptor and a radioactive tracer derived therefrom. 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] 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. Studies have 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 cancer, liver cancer, and testicular cancer, and its high expression is closely related to poor tumor prognosis. Given the connection between changes in DDR1 function and tumor development, DDR1 has become a new target for cancer research. Therefore, the development of new non-invasive DDR1 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, functional imaging with positron emission tomography (PET) 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, the defects of modern diagnostic technology can be overcome, providing a basis for early diagnosis, clinical staging, and efficacy evaluation of tumors, and evaluating prognosis.

[0005] Therefore, developing radiotracers targeting DDR1 receptors and using positron emission tomography to assess the expression level of DDR1 receptors 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 DDR1 receptor and a radioactive tracer derived therefrom.

[0007] In order to achieve the above technical objectives, the present invention adopts the following technical solutions: The first aspect of the present invention provides a compound targeting DDR1 receptor, the structural formula of which is shown in the following formula (I):

[0008] Formula (I).

[0009] The second aspect of the present invention provides an intermediate of the compound targeting DDR1 receptor described in the first aspect, and its structural formula is shown in the following formula (II):

[0010] Formula (II).

[0011] The third aspect of the present invention provides a method for preparing the compound targeting DDR1 receptor according to the first aspect, comprising the following steps: The compound represented by formula (II) is deprotected from Boc, 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 a compound targeting the DDR1 receptor.

[0012] The fourth aspect of the present invention provides a radioactive tracer, comprising the compound targeting DDR1 receptor described in the first aspect or the compound targeting DDR1 receptor prepared by the preparation method described in the third aspect and a radioactive nuclide.

[0013] A fifth aspect of the present invention provides a method for preparing the radioactive tracer according to the fourth aspect, comprising: After the radioactive nuclide is mixed and reacted with the compound targeting DDR1 receptor, a radioactive tracer is obtained.

[0014] The sixth aspect of the present invention provides use of the radioactive tracer described in the fourth aspect or the radioactive tracer prepared by the preparation method described in the fifth aspect in preparing a preparation for detecting the expression level of DDR1 receptor in tumors.

[0015] The seventh aspect of the present invention provides use of the radioactive tracer described in the fourth aspect or the radioactive tracer prepared by the preparation method described in the fifth aspect in preparing a preparation for diagnosing tumors with high expression of DDR1 receptor.

[0016] The beneficial effects of the present invention are: (1) The radioactive tracer provided by the present invention has a strong receptor binding affinity with the DDR1 receptor, can accurately locate the DDR1 receptor in vivo, has excellent in vivo targeting performance, and can achieve the purpose of tumor molecular imaging through nuclear medicine imaging.

[0017] (2) The present invention realizes non-invasive visualization of DDR1 receptor molecule expression, examines the tumor imaging effect of radioactive tracers through small animal PET / CT, and realizes non-invasive diagnosis of tumors, so it has good clinical application prospects.

[0018] (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

[0019] 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.

[0020] Figure 1 A synthetic route of the compound SDUHYX01 targeting the DDR1 receptor as shown in formula (I); Figure 2 is the high-resolution mass spectrum of compound 1; Figure 3 is the H NMR spectrum of compound 1; Figure 4 is a high-resolution mass spectrum of the compound represented by formula (II); Figure 5 High-resolution mass spectrometry of SDUHYX01, a compound targeting DDR1 receptor; Figure 6 For radioactive tracers 68 Ga]Ga-SDUHYX01 radiochemical purity test chart; Figure 7 For radioactive tracers 68 Results of the cellular uptake and internalization experiments of Ga]Ga-SDUHYX01; Figure 8 For radioactive tracers 68 Ga]Ga-SDUHYX01 cell saturation experimental results; Fig. 9 For radioactive tracers 68 Blood clearance curve of Ga]Ga-SDUHYX01; Fig.10 For radioactive tracers 68 PET / CT imaging of Ga]Ga-SDUHYX01 in tumor-bearing mice; Fig.11 For radioactive tracers 68 Biodistribution of Ga]Ga-SDUHYX01 in vivo. DETAILED DESCRIPTION

[0021] 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.

[0022] 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.

[0023] The first typical embodiment of the present invention provides a compound targeting DDR1 receptor, the structural formula of which is shown in the following formula (I):

[0024] Formula (I).

[0025] The compound represented by formula (I), in addition to the small molecule entity having the above structure, the physiologically acceptable salt of the compound also belongs to the technical solution under the same concept as the first aspect of the present invention, and belongs to the technical content of the present invention.

[0026] 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.

[0027] A second typical embodiment of the present invention provides an intermediate of the compound targeting DDR1 receptor according to the first aspect, and its structural formula is shown in the following formula (II):

[0028] Formula (II).

[0029] A third typical embodiment of the present invention provides a method for preparing the compound targeting DDR1 receptor according to the first aspect, comprising the following steps: The compound represented by formula (II) is deprotected from Boc, 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 a compound targeting the DDR1 receptor.

[0030] In one or more embodiments, 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 trifluoroacetic acid is removed by concentration.

[0031] 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.

[0032] 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: 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.

[0033] Preferably, the organic solvent is N,N-dimethylformamide (DMF).

[0034] In one or more embodiments, the molar ratio of the compound represented by formula (II) to the chelating agent tetraazacyclododecane tetraacetic acid-succinimide ester is 1:(0.9-1.2), preferably 1:1.

[0035] In one or more embodiments, the molar ratio of the compound represented by formula (II) to N,N-diisopropylethylamine is 1:(9-10), preferably 1:9.5.

[0036] A fourth typical embodiment of the present invention provides a radioactive tracer, comprising the compound targeting DDR1 receptor described in the first aspect or the compound targeting DDR1 receptor prepared by the preparation method described in the third aspect and a radioactive nuclide.

[0037] In one or more embodiments, the radionuclide is selected from 18 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, 64Cu, 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.

[0038] Preferably, the structural formula of the radioactive tracer is as shown in the following formula (III):

[0039] Formula (III).

[0040] A fifth typical embodiment of the present invention provides a method for preparing the radioactive tracer according to the fourth aspect, comprising: After the radioactive nuclide is mixed and reacted with the compound targeting DDR1 receptor, a radioactive tracer is obtained.

[0041] A sixth typical embodiment of the present invention provides use of the radioactive tracer described in the fourth aspect or the radioactive tracer prepared by the preparation method described in the fifth aspect in preparing a preparation for detecting the expression level of DDR1 receptor in tumors.

[0042] A seventh typical embodiment of the present invention provides use of the radioactive tracer described in the fourth aspect or the radioactive tracer prepared by the preparation method described in the fifth aspect in preparing a preparation for diagnosing tumors with high expression of DDR1 receptor.

[0043] 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.

[0044] 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.

[0045] In the present invention, the DDR1 receptor high expression tumor model is selected from the HT-29 cell colon cancer model.

[0046] Example 1 Figure 1 The synthetic route of the compound SDUHYX01 targeting DDR1 receptor shown in formula (I) is as follows: Figure 1 , synthesized the compound SDUHYX01 targeting the DDR1 receptor.

[0047] 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) were dissolved in DMF (5 mL), reacted at 25 °C for 12 hours, filtered, concentrated and purified by column chromatography (SiO2) to obtain compound 1 (1633.5 mg, yield 90%). The high-resolution mass spectrum of compound 1 is shown in FIG. Figure 2 As shown, the H NMR spectrum of compound 1 is as follows Figure 3 shown.

[0048] Compound 1 (1633.5 mg, 4.5 mmol) was dissolved in 5 mL methanol, Pd / C (Pd loading rate was 10%, 490 mg) was added, and the reaction was carried out under hydrogen atmosphere for 16 hours. After filtration, the product and 3-(2-pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzoic acid (1385 mg, 5 mmol) were dissolved in 5 mL DMF, and 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU) (2578 mg, 6.75 mmol) and DIPEA (1451 mg, 11.25 mmol) were added. The reaction was carried out 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 shown in FIG. Figure 4 shown.

[0049] The compound represented by formula (II) (35.5 mg, 0.06 mmol) was dissolved in 2 mL trifluoroacetic acid (TFA) and dichloromethane (DCM) (volume ratio 1:4), reacted at room temperature for 30 min, concentrated to remove TFA, the de-Boc protected mixture and DOTA-NHS (30 mg, 0.06 mmol) were dissolved in 1 mL DMF, DIPEA (74.2 mg, 0.57 mmol) was added, reacted at room temperature for 10 h, 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 compound SDUHYX01 targeting DDR1 receptor (28.5 mg, yield 54%), i.e., the compound represented by formula (I). The high-resolution mass spectrometry results of the compound SDUHYX01 targeting DDR1 receptor are shown in Figure 5.

[0050] Example 2 The compound SDUHYX01 (4 nmol) targeting the DDR1 receptor 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 15 min to obtain the radioactive tracer [ 68 Ga]Ga-SDUHYX01.

[0051] The radioactive tracer prepared in this example [ 68 The radiochemical purity of Ga]Ga-SDUHYX01 was tested by analytical HPLC with a radioactivity detector. The HPLC results are shown in Figure 6 As shown, from Figure 6 As can be seen in the figure, the radiotracer [ 68 The radiochemical purity of Ga]Ga-SDUHYX01 is greater than 95%.

[0052] 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.

[0053] Table 1 HPLC elution conditions

[0054] Example 3 In vitro and in vivo stability studies: For in vitro serum stability studies: 10 μL of radioactive tracer [ 68 Ga]Ga-SDUHYX01 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.

[0055] For in vivo stability studies: healthy NSG female mice were used to evaluate the radiotracer [ 68 The metabolic stability of Ga]Ga-SDUHYX01 in vivo. Each female mouse was injected with about 37 MBq of radioactive tracer [ 68 Ga]Ga-SDUHYX01, 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.

[0056] The results of in vitro and in vivo stability studies are shown in Table 2.

[0057] Table 2 Results of in vitro and in vivo stability studies

[0058] It can be seen from Table 2 that the radiotracer [ 68 Ga]Ga-SDUHYX01 has good stability in vivo and in vitro and can be used for subsequent experimental studies.

[0059] Example 4 Hydrophilicity and lipophilicity determination: 10 μL radiotracer [ 68 Ga]Ga-SDUHYX01 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 count of the organic phase / radioactivity count of the aqueous phase)], and the radioactive tracer [ 68 The log D of Ga]Ga-SDUHYX01 is -1.25±0.02. The experimental results show that the radiotracer [ 68 Ga]Ga-SDUHYX01 has certain hydrophilicity.

[0060] Example 5 Cellular uptake, internalization and saturation experimental studies: (1) Cell uptake and internalization experiment: For the cell uptake and internalization experiment, HT-29 cells were cultured at 5×10 5 Cells were seeded at a density of 1 / well in 12-well plates and incubated at 37°C with radiotracer [ 68 Ga]Ga-SDUHYX01 (100 nM) was co-incubated for 30, 60 and 120 minutes. To evaluate the specificity of uptake, a blocking experiment was performed using a 1000-fold molar concentration of the DDR1-targeted inhibitor 7rh. After incubation, the cells were washed three times with PBS, incubated with 0.05 M glycine buffer (pH = 2.8) for 10 minutes, washed three times with PBS, all the fluid was collected, lysed with 1 M NaOH solution, and the radioactivity of the collected fluid and cell suspension was quantified using a γ counter. The results are shown in Figure 7 As shown, from Figure 7 The radioactive tracer [ 68 The cellular uptake of Ga]Ga-SDUHYX01 increased over time and had a high internalization efficiency, compared with the radiotracer [ 68 Ga]Ga-SDUHYX01 uptake was significantly reduced, indicating that the radiotracer [ 68 Ga]Ga-SDUHYX01 binds specifically to the DDR1 receptor.

[0061] The structure of DDR1 targeting inhibitor 7rh is shown below: .

[0062] (2) Cell saturation experiment: To evaluate the radiotracer 68 The binding affinity of Ga]Ga-SDUHYX01 to DDR1 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 radiotracer [ 68 The cells were incubated with 1000-fold molar concentrations of DDR1-targeted inhibitor 7rh at 1000-fold molar concentrations for 1 h. After incubation, the radioactivity of the cell suspension was measured using a gamma counter, and the data were analyzed by nonlinear regression using GraphPadPrism 5.0 to determine K. d The result is Figure 8 As shown, from Figure 8 As can be seen in the figure, the radiotracer [ 68 Ga]Ga-SDUHYX01 has a high binding affinity to DDR1 receptor, and the radiotracer [ 68 Ga]Ga-SDUHYX01 K d The value was 61.81±0.43 nM. When incubated with 7rh solution, the radioactive tracer [ 68 The binding of Ga]Ga-SDUHYX01 to DDR1 receptor was significantly blocked, indicating that its binding to DDR1 receptor is specific.

[0063] Example 6 Pharmacokinetic properties studies Eight-week-old female BALB / c mice were injected with radiotracer via the tail vein. 68 Ga]Ga-SDUHYX01 (0.2 mL, 7.4 MBq) was injected, and blood samples were collected from the tail vein at 1, 3, 5, 10, 15, 30, 60, 90, and 120 min after injection. The samples were weighed and their radioactivity was measured using a γ counter. The pharmacokinetic curves were characterized using DAS software. The results are shown in Fig. 9As 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 radioactive tracer [ 68 The blood clearance curve of Ga]Ga-SDUHYX01 conformed to the two-compartment model, with the distribution phase half-life (T1 / 2α) of 0.93±0.11 minutes and the elimination phase half-life (T1 / 2β) of 53.07±2.26 minutes, indicating a moderate blood metabolism time.

[0064] Example 8 Small Animal PET / CT Imaging: Under anesthesia with 2% isoflurane in oxygen, a Mediso NanoScan μ-PET / CT scanner was used after injection of radiotracer [ 68 PET / CT imaging was performed 30 and 60 minutes after the administration of Ga]Ga-SDUHYX01 (0.2 mL, 7.4 MBq). HT-29 tumor-bearing mice (shoulder subcutaneous tumor) were randomly divided into an experimental group and a blocking group (n=3). In the blocking group, mice were simultaneously injected with radioactive tracer [ 68 Ga]Ga-SDUHYX01 and DDR1 targeted inhibitor 7rh (20 mg / kg). PET / CT images were reconstructed using Nucline NanoScan3.00 software and subsequently analyzed using InterView FUSION 3.0 software. Fig.10 As shown, the radiotracer [ 68 Ga]Ga-SDUHYX01 showed excellent imaging effect at 60 minutes (SUV: 0.56±0.03), but due to its strong lipophilicity, the tumor background was relatively low at 30 minutes. In the blocking group, tumor uptake was significantly reduced, suggesting that the radiotracer [ 68 Ga]Ga-SDUHYX01 is highly specific for DDR1 receptor uptake.

[0065] Example 9 Biodistribution studies: In the biodistribution study, HT-29 tumor-bearing mice (subcutaneous tumors in the shoulder) were injected with radiotracer via the tail vein. 68 Ga]Ga-SDUHYX01 (0.1 mL, 3.7 MBq). Tumor-bearing mice were killed 30 minutes or 60 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.11 As shown, the biodistribution results were consistent with the PET imaging results. At 60 minutes, the radiotracer [ 68 Ga]Ga-SDUHYX01 showed high tumor uptake and good tumor-to-background ratio, but due to its high relative lipophilicity, the tumor-to-liver ratio (ratio of radioactivity taken up by tumor to radioactivity taken up by liver) was low at 30 minutes.

[0066] 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 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.

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 The invention comprises the compound targeting DDR1 receptor according to claim 1 or the compound targeting DDR1 receptor prepared by the preparation method according to claim 3 and a radionuclide.

6. The radioactive tracer according to claim 5, characterized in that The radionuclide is selected from 18 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.

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

8. 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.

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

10. Use of the radioactive tracer according to claim 5 or the radioactive tracer prepared by the preparation method according to claim 8 in preparing a preparation for diagnosing tumors with high expression of DDR1 receptor.

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