Self-fixing type hydrogen peroxide imaging tracer agent and preparation method and application thereof

Abstract

The invention relates to a self-immobilized hydrogen peroxide imaging tracer agent as well as a preparation method and application thereof, and belongs to the technical field of nuclear medicine. The invention provides a series of self-fixing type hydrogen peroxide imaging tracers based on aryl boric acid ester. The tracers comprise [18F] HYAS, [18F] HYAT and the like. The series of tracers are high in self-fixing capacity and can react with H2O2 to form QM intermediates, so that the QM intermediates and nucleophilic reagents in biomacromolecules form covalent bonds; in addition, the series of tracers have the physicochemical property of being capable of penetrating through the blood brain barrier; meanwhile, experiments show that the series of tracers can distinguish tissues with different H2O2 concentrations in vivo, and in animal brains treated by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, ingestion increase of the series of tracers can be observed, and the series of tracers have very strong H2O2 responsiveness. In conclusion, the series of tracers have great application prospects in non-invasive imaging of H2O2 in the brain.

Description

Technical Field

[0001] The present invention relates to a self-fixing hydrogen peroxide imaging tracer, a preparation method thereof, and an application thereof, belonging to the technical field of nuclear medicine. Background Art

[0002] Neurodegenerative diseases are a class of chronic diseases characterized by the gradual loss and functional degradation of neurons and myelin sheaths. These diseases lead to the gradual decline of the nervous system, affecting functions such as cognition, movement, emotion, and perception. Oxidative stress (OS) plays a crucial role in the occurrence and development of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). The brain has a high oxygen demand, and the brain, which accounts for only 2% of the body weight, consumes 20% of the body's oxygen supply. In addition, the brain contains a high concentration of polyunsaturated fatty acids and has a poor antioxidant defense ability. These factors make the brain extremely vulnerable to oxidative stress. Oxidative stress is caused by the uncontrolled accumulation of reactive oxygen species (ROS) in cells and tissues. Physiological levels of ROS are crucial for maintaining the normal physiological functions of the body. However, excessive ROS can cause oxidative damage to biomolecules such as proteins, lipids, and nucleic acids, ultimately impairing the normal functions of cells. Hydrogen peroxide (H2O2), as an important ROS, is overexpressed in the early stages of AD and PD and is involved in disease progression. Evaluating the level of H2O2 in the brain is considered a valuable tool for detecting neurodegenerative diseases and exploring their pathogenesis, contributing to the early diagnosis of neurodegenerative diseases and helping to deeply understand the relationship between ROS and the pathology of neurodegenerative lesions.

[0003] So far, various H2O2 probes have been developed, including fluorescent probes, chemiluminescent probes, and PET tracers. Among them, PET imaging can detect picomolar concentrations of targets using extremely low tracer doses (pM - nM), and the penetration depth is not limited. Due to the high reactivity of H2O2, responsive probes are usually employed in the design of probes targeting H2O2. Responsive probes undergo physical and chemical transformations after being activated by H2O2, generating enhanced signals in pathological tissues. The design principle of responsive probes is generally to regulate the penetration ability through biological barriers (such as cell membranes and the blood - brain barrier BBB) by responding to ROS, enabling them to accumulate in tissues rich in ROS. Different from fluorescent probes that can "turn on" fluorescence in the presence of H2O2, PET tracers continuously emit radioactive signals. As a responsive probe, self - immobilizing probes can form covalent bonds with nucleophiles around biomacromolecules, facilitating their retention in diseased tissues. This property is particularly advantageous for detecting short - lived substances such as ROS. At present, various scaffolds have been utilized to develop self - immobilizing probes. Among them, quinomethide (QM) has attracted much attention due to its ability to react rapidly with nucleophilic donors of biomolecules under physiological conditions. However, to date, there have been no reports on QM - based PET tracers targeting H2O2. Summary of the Invention

[0004] To solve the above problems, the present invention provides a self - immobilizing hydrogen peroxide imaging tracer, and the tracer has the following structure:

[0005]

[0006] In the formula, R is

[0007] The present invention also provides a method for preparing the above - mentioned tracer, and the method includes: when R is , the method includes: mixing compound 1F and dichloromethane containing trifluoroacetic acid and reacting to obtain a reaction product; mixing the reaction product and 18 F]FBA in methanol and reacting to obtain the above - mentioned self - immobilizing hydrogen peroxide imaging tracer;

[0008] When R is , the method includes: mixing compound 1F and dichloromethane containing trifluoroacetic acid and reacting to obtain a reaction product; mixing the reaction product and 18 F]FBA in methanol and reacting to obtain the above - mentioned self - immobilizing hydrogen peroxide imaging tracer;

[0009] The compound 1F has the following structure:

[0010]

[0011] Compound 2F has the structure shown below:

[0012]

[0013] In one embodiment of the present invention, the preparation method of Compound 1F includes: mixing 4-bromo-DL-mandelic acid, N-Boc-1,6-hexanediamine, 1-hydroxybenzotriazole, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N,N-diisopropylethylamine and reacting them to obtain Compound 1A; mixing Compound 1A and diethylaminosulfur difluoride and reacting them to obtain Compound 1B; mixing Compound 1B, bis(pinacolato)diboron, potassium acetate and bis(diphenylphosphino)ferrocene-palladium dichloride dichloromethane complex and reacting them to obtain Compound 1C; mixing Compound 1C and diethanolamine and reacting them to obtain Compound 1D; mixing Compound 1D and trifluoroacetic acid and reacting them to obtain Compound 1E; mixing Compound 1E, (tert-butoxycarbonyl-aminooxy)acetic acid, 1-hydroxybenzotriazole, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N,N-diisopropylethylamine and reacting them to obtain Compound 1F;

[0014] Compound 1A has the structure shown below:

[0015]

[0016] Compound 1B has the structure shown below:

[0017]

[0018] Compound 1C has the structure shown below:

[0019]

[0020] Compound 1D has the structure shown below:

[0021]

[0022] Compound 1E has the structure shown below:

[0023]

[0024] In one embodiment of the present invention, the preparation method of the compound 2F includes: reacting N-(3-bromopropyl)phthalimide, N-tert-butoxycarbonylhydroxylamine and 1,8-diazabicycloundec-7-ene to obtain the compound 2A; reacting the compound 2A and hydrazine hydrate to obtain the compound 2B; reacting the compound 2B, 4-bromo-DL-mandelic acid, 1-hydroxybenzotriazole, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N,N-diisopropylethylamine to obtain the compound 2C; reacting the compound 2C and diethylaminosulfur trifluoride to obtain the compound 2D; reacting the compound 2D, potassium acetate and bis(diphenylphosphino)ferrocene-palladium dichloride dichloromethane complex to obtain the compound 2E; reacting the compound 2E and diethanolamine to obtain the compound 2F;

[0025] The compound 2A has the following structure:

[0026]

[0027] The compound 2B has the following structure:

[0028]

[0029] The compound 2C has the following structure:

[0030]

[0031] The compound 2D has the following structure:

[0032]

[0033] The compound 2E has the following structure:

[0034]

[0035] The present invention also provides the application of the above tracer in the preparation of a hydrogen peroxide imaging agent or a product for detecting diseases, and the diseases include neurodegenerative diseases, tumors, arthritis and / or cardiovascular and cerebrovascular diseases.

[0036] In one embodiment of the present invention, the neurodegenerative diseases include Alzheimer's disease and / or Parkinson's disease.

[0037] In one embodiment of the present invention, the product is a detection kit.

[0038] The present invention also provides a hydrogen peroxide imaging agent, and the components of the imaging agent include the above tracer, and the diseases include neurodegenerative diseases, tumors, arthritis and / or cardiovascular and cerebrovascular diseases.

[0039] The present invention also provides a product for detecting neurodegenerative diseases, and the composition of the imaging agent contains the above-mentioned tracer.

[0040] In one embodiment of the present invention, the neurodegenerative diseases include Alzheimer's disease and / or Parkinson's disease.

[0041] In one embodiment of the present invention, the product is a detection kit.

[0042] The technical solution of the present invention has the following advantages:

[0043] The present invention provides a series of self-immobilized hydrogen peroxide imaging tracers, including 18 F]HYAS and 18 F]HYAT, etc. This series of tracers has the following advantages:

[0044] First, arylboronic acid and arylboronic acid esters are the most commonly used response groups for constructing targeted H2O2 probes. When modified with a suitable leaving group (such as fluoromethyl or carbamate), arylboronic acid and arylboronic acid esters can be converted into QM in the presence of H2O2, and thus can further react with nucleophiles. The series of self-immobilized hydrogen peroxide imaging tracers of the present invention are designed based on arylboronic acid. Therefore, this series of tracers have strong self-immobilization ability, can react with H2O2 to form QM intermediates, and thus quickly react with nucleophiles such as amino groups widely present in various biological macromolecules to form covalent bonds, so as to enhance their uptake in tissues with a higher H2O2 level.

[0045] Second, considering that reactive oxygen species will be generated during the radiolabeling process, the presence of antioxidants helps to improve the radiochemical yield. And preliminary experiments show that sodium ascorbate is tolerable in the reaction of benzaldehyde and hydroxylamine. Therefore, the present invention selects 4- 18 F]fluorobenzaldehyde ( 18 F]FBA) as the structural unit for radiolabeling, and a hydroxylamine group is introduced into the self-immobilized hydrogen peroxide imaging tracer, so as to effectively improve the radiochemical yield of the tracer.

[0046] Third, the series of self-immobilized hydrogen peroxide imaging tracers of the present invention use linkers with different lengths to connect 18 F]FBA and the self-immobilized part, so as to endow this series of self-immobilized hydrogen peroxide imaging tracers with physical and chemical properties that can cross the blood-brain barrier (BBB).

[0047] Fourth, animal experiments have shown that this series of self-immobilized hydrogen peroxide imaging tracers can distinguish tissues with different H2O2 concentrations in vivo. Moreover, an increased uptake of this series of self-immobilized hydrogen peroxide imaging tracers was observed in the brains of animals treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Therefore, the series of self-immobilized hydrogen peroxide imaging tracers of the present invention has a strong H2O2 responsiveness.

[0048] In summary, this series of tracers can dynamically and real-time monitor the changes in brain H2O2 levels through PET imaging, and has great application prospects in non-invasive imaging of brain H2O2. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 : Synthetic route of the non-radioactive compound HYAS.

[0050] Figure 2 : 1 1H-NMR spectrum of HYAS.

[0051] Figure 3 : Mass spectrum of HYAS.

[0052] Figure 4 : Synthetic route of the non-radioactive compound HYAT.

[0053] Figure 5 : 1 1H-NMR spectrum of HYAT.

[0054] Figure 6 : Mass spectrum of HYAT.

[0055] Figure 7 : High-performance liquid chromatography (HPLC) spectra of 5 μM HYAS (a) and HYAT (b) after incubation with 50 μM ethylamine, 100 μM hydrogen peroxide, and 50 μM ethylamine at 37 °C for 1 hour.

[0056] Figure 8 : Mass spectrometry analysis chart of EtNH2-labeled HYAS.

[0057] Figure 9 : Mass spectrometry analysis chart of EtNH2-labeled HYAT.

[0058] Figure 10 : Activation of 5 μM HYAS or HYAT for 1 hour in the presence of 100 μM hypochlorite ion (ClO - ), peroxynitrite anion (ONOO - ) or hydrogen peroxide (H2O2).

[0059] Figure 11 : Response mechanism of the tracer (after being activated by H2O2, the tracer first forms OH intermediates, and then undergoes a 1,6-elimination reaction to generate QM intermediates. These QM intermediates can quickly react with biomolecules, thereby enhancing the uptake of the tracer in tissues with higher H2O2 levels).

[0060] Figure 12 : Tracer 18 F]HYAS and 18 Radioactive synthesis routes of

[0061] Figure 13 : 18 F]HYAS and 18 Positron emission tomography (PET) images of 18 F]HYAS and 18 F]HYAT in Balb / c-nu mice (a) and time-radioactivity curves of the uptake of

[0062] Figure 14 : 18 F]HYAS and 18 Positron emission tomography (PET) images of 18 F]HYAS and 18 F]HYAT in the brains of SD rats (scanning time: 10 to 20 minutes) (a) and time-radioactivity curves of the uptake of

[0063] Figure 15 : 18 Positron emission tomography (PET) images of 18 F]HYAT in the brains of C57BL / 6 mice (scanning time: 5 to 15 minutes) (a) and time-radioactivity curves of the uptake of Detailed implementation methods

[0064] The following embodiments are provided to better understand the present invention further. It is not limited to the best embodiment described, and does not limit the content and protection scope of the present invention. Any product identical or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with those of other prior arts falls within the protection scope of the present invention.

[0065] For those embodiments without specific experimental steps or conditions noted below, the operations or conditions of the conventional experimental steps described in the literature in this field can be followed. For the reagents or instruments without the manufacturer noted, they are all conventional reagent products that can be obtained through commercial purchase.

[0066] Example 1: A non-radioactive compound HYAS

[0067] This example provides a non-radioactive compound HYAS, and the non-radioactive compound HYAS has the following structure:

[0068]

[0069] Example 2: A method for preparing the non-radioactive compound HYAS

[0070] This example provides a method for preparing the non-radioactive compound HYAS described in Example 1 (the synthesis route is shown in Figure 1 ), and the specific steps are as follows:

[0071] Step 1: 4-Bromo-DL-mandelic acid (1.5 g, 5.591 mmol, CAS: 6940-50-7), N-Boc-1,6-hexanediamine (1.7 mL, 7.702 mmol, CAS: 65915-94-8), 1-Hydroxybenzotriazole (HOBt, 204 mg, 1.512 mmol, CAS: 2592-95-2), 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 2.20 g, 11.511 mmol, CAS: 25952-53-8) and N,N-Diisopropylethylamine (DIPEA, 2.01 mL, 11.511 mmol) were successively added to 5 mL of N,N-Dimethylformamide (DMF). After that, the mixture was stirred (rotation speed 200 rpm) at room temperature (25 °C) for 48 hours to obtain a reaction product. The reaction product was diluted with ethyl acetate (EA, 50 mL), and then washed successively with saturated ammonium chloride solution (50 mL), saturated sodium bicarbonate solution (50 mL) and saturated brine (50 mL). The organic phase was taken. The organic phase was first dried over anhydrous sodium sulfate, then concentrated by a rotary evaporator, and further purified by silica gel column chromatography (using a mixed solution of dichloromethane and methanol as the eluent, where dichloromethane / methanol = 30 / 1, v / v) to obtain compound 1A in the form of a white solid (2.42 g, yield: 72%). The mass spectrometry (ESI) data of compound 1A was: [M+Na] + C 19 H 29 BN2NaO4, theoretical values: 451.12, 453.12, measured value: 453.36.

[0072] Step 2: Compound 1A (112 mg, 0.261 mmol) was dissolved in 5 mL of dichloromethane to obtain a solution. After the solution was cooled to -20 °C, diethylaminosulfur trifluoride (65 μL, 0.512 mmol, CAS: 38078-09-0) was added dropwise to the solution, and then the mixture was stirred and reacted in an ice bath for 3 hours to obtain a reaction product. After quenching the reaction by adding 500 μL of methanol dropwise to the reaction product at 0 °C, the reaction product was first placed at room temperature for 0.5 hour, then the solvent was evaporated by a rotary evaporator, and further purified by silica gel column chromatography (using a mixed solution of n-hexane and ethyl acetate as the eluent, where n-hexane / ethyl acetate = 3 / 1, v / v) to obtain compound 1B in the form of a colorless liquid (80 mg, yield: 72%). The mass spectrometry (ESI) data of compound 1B was: [M+Na] + C 19 H 28 BrFN2NaO3, theoretical values: 453.12, 454.12, measured value: 453.33.

[0073] Step 3: Dissolve compound 1B (285 mg, 0.630 mmol), bis(pinacolato)diboron (320 mg, 1.260 mmol, CAS: 73183-34-3), potassium acetate (180 mg, 1.890 mmol) and bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (50 mg, 0.060 mmol, CAS: 95464-05-4) in 5 mL of deoxygenated 1,4-dioxane. Then, stir the reaction mixture at 90 °C for 18 h under nitrogen protection to obtain the reaction product. After evaporating 1,4-dioxane using a rotary evaporator, redissolve the residue in dichloromethane (10 mL), filter to remove insoluble impurities, and purify by silica gel column chromatography (using a mixture of n-hexane and ethyl acetate as the eluent, where n-hexane / ethyl acetate = 2 / 1, v / v) to obtain colorless oily compound 1C (98 mg, yield: 80%). The mass spectrometry (ESI) data of compound 1C is: [M+Na]+C 25 H 40 BFN2NaO5, theoretical value: 501.29, measured value: 501.50.

[0074] Step 4: Dissolve compound 1C (194 mg, 0.40 mmol) in 5 mL of anhydrous tetrahydrofuran to obtain a solution. Add diethanolamine (232 μL, 2.400 mmol, CAS: 111-42-2) to the solution and stir the reaction mixture at room temperature for 12 h to obtain the reaction product. After evaporating tetrahydrofuran using a rotary evaporator, redissolve the residue in dichloromethane (20 mL), wash with water (20 mL), and collect the organic phase. Dry the organic phase over anhydrous sodium sulfate, concentrate it using a rotary evaporator, and purify by silica gel column chromatography (using a mixture of dichloromethane and methanol as the eluent, where dichloromethane / methanol = 15 / 1, v / v) to obtain colorless oily compound 1D (100 mg, yield: 62%). The mass spectrometry (ESI) data of compound 1D is: [M+Cl] - C 19 H 30 BClFN2O5, theoretical value: 431.19, measured value: 431.37.

[0075] Step 5: Dissolve compound 1D (100 mg, 0.25 mmol) in 2 mL of dichloromethane to obtain a solution. Add trifluoroacetic acid (200 μL) to the solution at 0 °C, then transfer the mixture to room temperature and stir for 1 h to obtain the reaction product. Concentrate the reaction product using a rotary evaporator to obtain compound 1E (74 mg, yield: 100%).

[0076] Step 6: Dissolve compound 1E in dry dichloromethane (10 mL) to obtain a solution. Add (tert-butoxycarbonyl-aminooxy)acetic acid (0.098 g, 0.5 mmol, CAS: 42989-85-5), HOBt (0.058 g, 0.41 mmol), EDCI (0.124 g, 0.62 mmol), and DIPEA (0.376 mL, 2.09 mmol) to the solution, and then let it stand overnight (16 hours) at room temperature to obtain a reaction product. Dilute the reaction product with 50 mL of dichloromethane, wash it with water (20 mL), and take the organic phase. Dry the organic phase over anhydrous sodium sulfate first, then concentrate it by a rotary evaporator, and further purify it by silica gel column chromatography (using a mixed solution of dichloromethane and methanol as the eluent, where dichloromethane / methanol = 20 / 1, v / v) to obtain colorless oily compound 1F (98 mg, yield: 78%). The hydrogen nuclear magnetic resonance spectrum ( 1 1H-NMR, 400 MHz, d6-DMSO) data of compound 1F are as follows: δ 10.31 (singlet, 1H), 8.43 (multiplet, J = 5.9 Hz, 1H), 8.11 (singlet, 2H), 7.99 (singlet, 1H), 7.84 - 7.78 (multiplet, 2H), 7.42 - 7.37 (multiplet, 2H), 5.83 (doublet, J = 4..8 Hz, 1H), 4.14 (singlet, 2H), 3.11 (quartet, J = 6.8 Hz, 4H), 1.41 (singlet, 13H), 1.24 (doublet, J = 3.1 Hz, 4H). The carbon nuclear magnetic resonance spectrum (13C-NMR, 100 MHz, d6-DMSO) data of compound 1F are as follows: δ 168.4, 168.0, 157.6, 134.6, 126.3, 126.3, 81.3, 79.7, 75.3, 40.6, 40.4, 40.2, 40.0, 39.7, 39.5, 39.3, 38.6, 32.3, 28.4, 26.5. The mass spectrum (ESI) data of compound 1F are: [M+Cl] - C 21 H 33 BClFN3O7, theoretical value: 504.21, measured value: 504.42.

[0077] Step 7: Dissolve compound 1F (15 mg, 0.032 mmol) in 2 mL of dichloromethane to obtain a solution. Add trifluoroacetic acid (200 μL) to the solution at 0 °C, then transfer it to room temperature and stir for 1 hour to obtain a reaction product. Concentrate the reaction product by a rotary evaporator to obtain compound 1G (12 mg, yield: 100%).

[0078] Step 8: Dissolve compound 1G (12 mg, 0.032 mmol) in 3 mL of methanol to obtain a solution; add 4-fluorobenzaldehyde (5.5 μL, 0.051 mmol, CAS: 459-57-4) to the solution, and stir the reaction at room temperature for 1 hour to obtain a reaction product; concentrate the reaction product by a rotary evaporator first, and then purify it by silica gel column chromatography (using a mixed solution of dichloromethane and methanol as the eluent, where dichloromethane / methanol = 20 / 1, v / v) to obtain a colorless oily compound HYAS (11 mg, yield 88%). The nuclear magnetic resonance analysis results of compound HYAS are shown in Figure 2 , and the mass spectrometry analysis results are shown in Figure 3 . The proton nuclear magnetic resonance spectrum of compound HYAS ( 1 H-NMR, 400 MHz, d6-DMSO) data are as follows: δ 8.44 - 8.38 (multiplet, 1H), 8.35 (singlet, 1H), 8.10 (singlet, 2H), 7.84 - 7.75 (multiplet, 3H), 7.71 - 7.62 (multiplet, 2H), 7.42 - 7.35 (multiplet, 2H), 7.33 - 7.21 (multiplet, 2H), 5.82 (doublet, J = 47.8 Hz, 1H), 4.49 (singlet, 2H), 3.11 - 3.05 (multiplet, 4H), 1.39 - 1.33 (multiplet, 4H), 1.22 - 1.20 (multiplet, 4H). The carbon nuclear magnetic resonance spectrum of compound HYAS (13C-NMR, 100 MHz, d6-DMSO) data are as follows: δ 168.8, 168.1, 167.9, 164.8, 162.4, 149.8, 138.1, 137.9, 135.6, 134.6, 129.8, 129.7, 128.6, 128.6, 126.2, 126.2, 116.5, 116.3, 92.3, 90.5, 73.2, 49.1, 40.6, 40.5, 40.4, 40.3, 40.2, 40.0, 39.8, 39.6, 39.4, 38.7, 38.5, 29.5, 29.3, 26.4. The mass spectrometry (ESI) data of compound HYAS are: [M + CF3COO] - C 25 H 28 BF5N3O7, theoretical value: 588.19, measured value: 588.41.

[0079] Example 3: A non-radioactive compound HYAT

[0080] This example provides a non-radioactive compound HYAT, and the non-radioactive compound HYAT has the following structure:

[0081]

[0082] Example 4: A method for preparing non-radioactive compound HYAT

[0083] This example provides a method for preparing the non-radioactive compound HYAT described in Example 3 (the synthesis route is shown in Figure 4 ), and the specific steps are as follows:

[0084] Step 1: Dissolve N-(3-bromopropyl)phthalimide (1.5 g, 5.591 mmol, CAS: 5460-29-7) and N-Boc hydroxylamine (1.48 g, 11.182 mmol, CAS: 36016-38-3) in 20 mL of anhydrous dichloromethane to obtain a solution; dropwise add 1,8-diazabicycloundec-7-ene (DBU, 4.18 ml, 27.955 mmol, CAS: 6674-22-2) to the solution, and stir the reaction at room temperature for 16 hours to obtain a reaction product; dilute the reaction product with 50 mL of dichloromethane, wash it with water (50 mL), and take the organic phase; dry the organic phase with anhydrous sodium sulfate first, then concentrate it by a rotary evaporator, and then purify it by silica gel column chromatography (using a mixed solution of n-hexane and dichloromethane as the eluent, where n-hexane / dichloromethane = 9 / 1, v / v) to obtain a colorless oily compound 2A (0.815 mg, yield: 46%). The mass spectrometry (ESI) data of compound 2A is: [M+Na] + C 16 H 20 N2NaO5, theoretical value 343.13, measured value: 343.45.

[0085] Step 2: Dissolve compound 2A (125 mg, 0.391 mmol) in 5 mL of methanol to obtain a solution; add hydrazine hydrate (379 μL, 7.810 mmol) to the solution, and let it stand overnight (16 hours) at room temperature to obtain a reaction product; evaporate the methanol from the reaction product by a rotary evaporator, first add dichloromethane (20 mL) to redissolve it, then wash it with water (20 mL), and take the organic phase; dry the organic phase with anhydrous sodium sulfate first, and then evaporate the solvent by a rotary evaporator to obtain a colorless oily compound 2B (23 mg, yield: 31%). The mass spectrometry (ESI) data of compound 2B is: [M+H] + C8H 19 N2O3, theoretical value: 191.14, measured value: 191.22.

[0086] Step 3: Add compound 2B (0.39 g, 2.005 mmol), 4-bromo-DL-mandelic acid (0.51 g, 2.212 mmol), 1-hydroxybenzotriazole (HOBt, 60 mg, 0.044 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 633 mg, 3.314 mmol) and N,N-diisopropylethylamine (DIPEA, 579 μL, 3.314 mmol) into 10 mL of N,N-dimethylformamide (DMF) successively. After that, stir and react at room temperature (25 °C) for 48 hours to obtain a reaction product. Dilute the reaction product with water (20 mL), extract with ethyl acetate (EA, 20 mL) to remove DMF and water-soluble impurities, and take the organic phase. Dry the organic phase with anhydrous sodium sulfate first, then evaporate ethyl acetate by a rotary evaporator, and further purify by silica gel column chromatography (using a mixed solution of dichloromethane and methanol as the eluent, where dichloromethane / methanol = 40 / 1, v / v) to obtain a colorless oily compound 2C (545 mg, yield: 61%). The mass spectrometry (ESI) data of compound 2C is: [M+H] + C 16 H 23 BrN2NaO5, theoretical values: 425.07, 427.07, measured value: 425.36.

[0087] Step 4: Dissolve compound 2C (0.55 g, 1.350 mmol) in 5 mL of dichloromethane to obtain a solution. Cool the solution to -20 °C, first add diethylaminosulfur trifluoride (180 μL, 2.560 mmol) dropwise to the solution, and then stir and react in an ice bath for 3 hours to obtain a reaction product. Quench the reaction by adding 500 μL of methanol dropwise to the reaction product at 0 °C. Then, let the reaction product stand at room temperature for 0.5 hour and further purify by silica gel column chromatography (using a mixed solution of n-hexane and ethyl acetate as the eluent, where n-hexane / ethyl acetate = 2 / 1, v / v) to obtain a colorless liquid compound 2D (254 mg, yield: 46%). The mass spectrometry (ESI) data of compound 2D is: [M+H]+C 16 H 22 BFN2NaO4, theoretical value: 427.06, measured value: 427.33.

[0088] Step 5: Dissolve compound 2D (254 mg, 0.630 mmol), bis(pinacolato)diboron (320 mg, 1.260 mmol), potassium acetate (180 mg, 1.890 mmol) and bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (50 mg, 0.060 mmol) in 5 mL of deoxygenated 1,4-dioxane, and then stir the reaction mixture at 90 °C for 18 h under nitrogen protection to obtain a reaction product. After evaporating 1,4-dioxane from the reaction product by a rotary evaporator, add dichloromethane (20 mL) to redissolve it, then filter to remove insoluble impurities, and further purify it by silica gel column chromatography (using a mixed solution of n-hexane and ethyl acetate as the eluent, where n-hexane / ethyl acetate = 2 / 1, v / v) to obtain a yellow oily compound 2E (104 mg, yield: 67%). The mass spectrometry (ESI) data of compound 2E is: [M+Na] + C 22 H 34 BFN2NaO6, theoretical value: 475.24, measured value: 475.52.

[0089] Step 6: Dissolve compound 2E (110 mg, 0.241 mmol) in 5 mL of anhydrous tetrahydrofuran to obtain a solution. Add diethanolamine (232 μL, 2.400 mmol) to the solution, and then stir the reaction mixture at room temperature for 12 h to obtain a reaction product. After evaporating tetrahydrofuran from the reaction product by a rotary evaporator, add dichloromethane (20 mL) to redissolve it, wash with water (20 mL), and take the organic phase. Dry the organic phase over anhydrous sodium sulfate first, then concentrate it by a rotary evaporator, and further purify it by silica gel column chromatography (using a mixed solution of dichloromethane and methanol as the eluent, where dichloromethane / methanol = 15 / 1, v / v) to obtain a colorless oily compound 2F (60 mg, yield: 68%). The 1H nuclear magnetic resonance spectrum of compound 2F 1The data of 1H-NMR (400 MHz, d6-DMSO) are as follows: δ 9.93 (singlet, 1H), 8.44 (triplet, J = 5.9 Hz, 1H), 8.11 (singlet, 2H), 7.76 (doublet, J = 7.8 Hz, 2H), 7.35 (doublet, J = 7.7 Hz, 2H), 5.80 (doublet, J = 47.6 Hz, 1H), 3.64 (triplet, J = 6.4 Hz, 2H), 3.20 - 3.13 (multiplet, 2H), 1.64 (multiplet, J = 6.7 Hz, 2H), 1.36 (singlet, 9H). The data of 13C-NMR (100 MHz, d6-DMSO) of compound 2F are: δ 168.4, 168.2, 156.8, 138.0, 137.8, 134.7, 126.3, 126.3, 92.3, 90.5, 79.7, 73.8, 40.6, 40.4, 40.2, 40.0, 39.7, 39.5, 39.3, 36.2, 28.6, 28.1. The data of the mass spectrum (ESI) of compound 2F are: [M-H] - C 16 H 23 BFN2O6, theoretical value: 369.16, measured value: 369.40.

[0090] Step 7: Dissolve compound 2F (10 mg, 0.027 mmol) in 2 mL of dichloromethane to obtain a solution; add trifluoroacetic acid (200 μL) to the solution at 0 °C, then transfer it to room temperature and stir for 1 hour to obtain a reaction product; concentrate the reaction product by a rotary evaporator to obtain compound 2G (7.3 mg, yield: 100%).

[0091] Step 8: Dissolve compound 2G (7 mg, 0.026 mmol) in 3 mL of methanol to obtain a solution; add 4-fluorobenzaldehyde (5.5 μL, 0.051 mmol) to the solution, then stir at room temperature for 1 hour to obtain a reaction product; first concentrate the reaction product by a rotary evaporator, and then purify it by silica gel column chromatography (using a mixed solution of dichloromethane and methanol as the eluent, where dichloromethane / methanol = 15 / 1, v / v) to obtain the white solid compound HYAT (9 mg, yield 90%). The results of nuclear magnetic resonance analysis of compound HYAT are shown in Figure 5 and the results of mass spectrometry analysis are shown in Figure 6 . The 1H-nuclear magnetic resonance spectrum of compound HYAT 1The data of 1H-NMR (400 MHz, d6-DMSO) were as follows: δ 8.49 (multiplet, J = 5.7 Hz, 1H), 8.19 (singlet, 1H), 8.12 (singlet, 2H), 7.77 (doublet, J = 7.7 Hz, 2H), 7.67 - 7.55 (multiplet, 2H), 7.36 (doublet, J = 7.6 Hz, 2H), 7.27 - 7.15 (multiplet, 2H), 5.81 (doublet, J = 47.7 Hz, 1H), 4.05 (multiplet, J = 6.4 Hz, 2H), 3.19 (multiplet, J = 6.9, 2.6 Hz, 2H), 1.79 (multiplet, J = 6.7 Hz, 2H). The carbon nuclear magnetic resonance spectrum of compound HYAT ( 13 13C-NMR (100 MHz, d6-DMSO) data were as follows: δ 168.4, 162.2, 148.2, 138.0, 137.8, 134.7, 129.6, 129.5, 126.3, 126.3, 116.5, 116.3, 92.3, 90.5, 71.9, 40.6, 40.4, 40.2, 40.0, 39.8, 39.6, 39.4, 36.0, 29.2. The mass spectrum (ESI) data of compound HYAT were: [M + CF3COO] - C 20 H 19 BF5N2O6, theoretical value: 489.13, measured value: 489.37.

[0092] Experimental Example 1: Self-fixation experiment of non-radioactive compounds

[0093] As a nucleophile, amino groups widely exist in various biological macromolecules, including proteins and enzymes. Therefore, to verify the self-fixation ability of non-radioactive compounds, this experimental example selected ethylamine (EtNH2) as a nucleophile model to study the reactivity of non-radioactive compounds with nucleophiles in the presence of H2O2. The specific process is as follows:

[0094] Experiment 1: Non-radioactive compound HYAS or HYAT (5 μM) was separately added to PBS buffer (pH = 7.4, 0.01 M) containing ethylamine (50 μM) or simultaneously containing ethylamine (50 μM) and H2O2 (100 μM) to obtain a mixed solution; the mixed solution was incubated at 37 °C for 1 hour; after the incubation ended, the incubated solution was analyzed by HPLC; after the analysis ended, the eluate was collected for electrospray ionization mass spectrometry (ESI-MS) analysis. The analysis results are shown in Figures 7 - 9 。

[0095] Experiment 2: Non-radioactive compounds HYAS or HYAT (5 μM) were separately added to PBS buffer (pH = 7.4, 0.01 M) containing H2O2 (100 μM), molsidomine (100 μM) or sodium hypochlorite (100 μM) to obtain a mixed solution; the mixed solution was incubated at 37 °C for 1 hour; after the incubation ended, the incubation solution was taken for analysis by HPLC; after the analysis ended, the area of the corresponding peak in HPLC was calculated, and the calculation results are shown in Figure 10 .

[0096] Experimental results: In the absence of H2O2, both non-radioactive compounds HYAS and HYAT remained intact after incubation with EtNH2 for 1 hour ( Figure 7 ). However, in the presence of H2O2 (100 μM), the peaks of non-radioactive compounds HYAS and HYAT disappeared after incubation, and new peaks were detected. Mass spectrometry (MS) analysis of the eluate showed that the new peaks appearing at 17.6 minutes and 17.8 minutes corresponded to the addition products of HYAS (EtNH2-labeled HYAS) and HYAT (EtNH2-labeled HYAT) with EtNH2 ( Figures 8 - 9 ). The results indicate that non-radioactive compounds HYAS and HYAT can form covalent bonds with nucleophiles in biological macromolecules after being activated by H2O2. In addition to the EtNH2-labeled products, other products were also formed. It is speculated that this may be due to the strong oxidizing property of H2O2 and the high reactivity of the QM intermediate. First, H2O2 can oxidize various organic compounds including amino groups and phenolic hydroxyl groups, resulting in the oxidation of the compounds in the sample. Second, the QM intermediate can also react with H2O2. These two factors may complicate the HPLC analysis results. It has been reported in the literature that other reactive oxygen species, mainly peroxynitrite (ONOO - ) and perchlorate (ClO - ), can activate aryl boronic esters. Therefore, the reactivity of the probe towards H2O2, ONOO - and ClO - was compared ( Figure 10 ). Among these three reactive oxygen species, H2O2 is the most effective reactive oxygen species for activating the probe, while ONOO - has the worst activity.

[0097] Example 5: A self-fixed hydrogen peroxide imaging tracer 18 F]HYAS

[0098] This example provides a self-fixed hydrogen peroxide imaging tracer 18 F]HYAS (for the response mechanism of the tracer, see Figure 11 ), and the tracer 18 F]HYAS has the following structure:

[0099]

[0100] Example 6: A method for preparing a self-fixed hydrogen peroxide imaging tracer 18 F]HYAS

[0101] This example provides a method for preparing the self-fixed hydrogen peroxide imaging tracer 18 F]HYAS described in Example 5 (for the radiochemical synthesis route of the tracer, see Figure 12 ), and the specific steps are as follows:

[0102] Pass 18 F]fluoride ions through a Sep-Pak Light QMA column (Waters Corporation), dry with 5 mL of anhydrous acetonitrile, and elute with methanol (1 mL) containing 4-formyl-N,N,N-trimethylanilinium trifluoromethanesulfonate (3 mg, CAS: 124915-02-2) to obtain 18 F]fluoride ion eluate; after evaporating methanol from the 18 F]fluoride ion eluate under reduced pressure at 60 °C, first add dimethyl sulfoxide (DMSO, 1.5 mL), and then react at 120 °C for 5 minutes to obtain a reaction product containing 18 F]FBA; dilute the reaction product containing 18 F]FBA with water (20 mL), first pass through a C18 Sep-Pak cartridge (Waters Corporation), and then elute with methanol (1 mL) to obtain 18 F]FBA eluate; add compound 1F (2.5 mg) to dichloromethane containing 50% (v / v) trifluoroacetic acid, and incubate at 25 °C for 1 hour to obtain an incubation product; concentrate the incubation product under vacuum to obtain a concentrated solution; add 18 F]FBA eluate (0.5 mL) and the concentrated solution (0.5 mL) to a methanol solution (0.2 mL) containing 2 mg / mL sodium ascorbate, and react at room temperature for 1 hour to obtain a reaction product; purify the reaction product by semi-preparative HPLC to obtain the self-fixed hydrogen peroxide imaging tracer 18 F]HYAS.

[0103] Detect the radiochemical yield and radiochemical purity of 18 F]HYAS by analytical HPLC, and the analysis results are shown in Figure 12 . The measured radiochemical yield is 10.4 ± 0.8%, the radiochemical purity > 90%, and the molar activity is 12.7 ± 0.9 GBq / μM.

[0104] Example 7: A self-fixed hydrogen peroxide imaging tracer 18F]HYAT

[0105] This example provides a self - immobilized hydrogen peroxide imaging tracer 18 F]HYAT (for the response mechanism of the tracer, see Figure 11 ), and the tracer 18 F]HYAT has the following structure:

[0106]

[0107] Example 8: A method for preparing a self - immobilized hydrogen peroxide imaging tracer 18 F]HYAT

[0108] This example provides a method for preparing the self - immobilized hydrogen peroxide imaging tracer 18 F]HYAT described in Example 7 (for the radiochemical synthesis route of the tracer, see Figure 12 ), and the specific steps are as follows:

[0109] On the basis of Example 6, compound 1F is replaced with compound 2F to obtain the self - immobilized hydrogen peroxide imaging tracer 18 F]HYAT.

[0110] The radiochemical yield and radiochemical purity of 18 F]HYAT are detected by analytical HPLC, and the analysis results are shown in Figure 12 . The measured radiochemical yield is 8.3 ± 1.0%, the radiochemical purity > 90%, and the molar activity is 11.5 ± 1.2 GBq / μM.

[0111] Experimental Example 2: In vitro stability experiment of the self - immobilized hydrogen peroxide imaging tracer

[0112] This experimental example provides an in vitro stability experiment of the self - immobilized hydrogen peroxide imaging tracer, and the specific process is as follows:

[0113] The non - radioactive compounds HYAS or HYAT, the tracers 18 F]HYAS or 18 F]HYAT are respectively mixed with PBS buffer (pH = 7.4, 0.01 M) containing sodium ascorbate (~0.01 mg / mL) at a volume ratio of 1:9 to obtain a mixed solution; the mixed solution is incubated at 37 °C for 4 hours; after the incubation ends, the incubated solution is taken for radio - high performance liquid chromatography (Radio - HPLC) analysis, and the analysis results are shown in Figure 12 .

[0114] From Figure 12It can be seen that both non-radioactive compounds and two self-immobilized hydrogen peroxide imaging tracers showed high stability, and no obvious degradation was observed in the HPLC chromatogram after incubation in PBS buffer for 4 hours.

[0115] Experimental Example 3: Experiment on the octanol-water partition coefficient of self-immobilized hydrogen peroxide imaging tracer

[0116] This experimental example provides an experiment on the octanol-water partition coefficient of self-immobilized hydrogen peroxide imaging tracer, and the specific process is as follows:

[0117] Take a centrifuge tube, first add 1 mL of deionized water and 1 mL of n-octanol, and then add the tracer 18 F]HYAS or 18 F]HYAT (~0.7 MBq) to obtain a mixed solution; after shaking the mixed solution for 5 min, centrifuge it at 6000 r / min for 5 min at high speed to separate the two phases; take 500 μL each of the n-octanol phase and the water phase into a radioimmunoassay tube, and then use a gamma counter to detect the radioactivity of the n-octanol phase and the water phase respectively and calculate LogP (LogP = LogC o / C w ), where C o represents the radioactive dose of the tracer in the n-octanol phase, and C w represents the radioactive dose of the tracer in the water phase. After the first test, add 500 μL of n-octanol and 500 μL of water to the original centrifuge tube again, shake, centrifuge, sample and measure LogP again; repeat the experiment multiple times until three consecutive measured LogP values are close, and take the average of the three groups of data as the octanol-water partition coefficient value, and the result is expressed as the average value ± standard deviation. Use the same method to detect the octanol-water partition coefficient of the tracer.

[0118] The experimental measurement showed that the octanol-water partition coefficients of the tracers 18 F]HYAS and 18 F]HYAT were 2.34 ± 0.14 and 2.09 ± 0.02 respectively, indicating that the lipophilicity of the probe meets the requirements of brain imaging probes.

[0119] Experimental Example 4: PET imaging experiment of self-immobilized hydrogen peroxide imaging tracer

[0120] This experimental example provides a PET imaging experiment of self-immobilized hydrogen peroxide imaging tracer. All animal experiments were approved by the Animal Ethics Committee of Jiangsu Institute of Atomic Medicine (JSINM-2023-040 and JSINM-2023-057), and the specific process is as follows:

[0121] Experiment 1: H2O2 (25 mM, 50 μL) prepared with physiological saline was injected into the left hind limb of Balb / c-nu mice (female, 6 - 8 weeks old, purchased from Cavens) to establish a high-level H2O2 region. Immediately after the injection of H2O2, 18 F]HYAS or 18 F]HYAT (5.55 MBq, 200 μL) was injected into the mice via the tail vein. After the injection, dynamic PET imaging of the lower limbs of the mice was performed on a small animal PET scanner (Siemens Inveon, Germany) for 1 hour. After the imaging, regions of interest (ROIs) were outlined for both thighs of the mice and quantitative analysis was performed using the ASIPro image processing software. The imaging and quantitative analysis results are shown in Figure 13 . The uptake of the region of interest (ROI) was expressed as the percentage of the injected dose per cubic centimeter (%ID / mL).

[0122] Experiment 2: 18 F]HYAS or 18 F]HYAT (14.8 MBq, 350 μL) was injected into Sprague-Dawley (SD) rats (female, 3 months old, purchased from Cavens) via the tail vein. After the injection, dynamic PET imaging of the heads of the rats was performed on a small animal PET scanner (Siemens Inveon, Germany) for 1 hour. After the imaging, regions of interest (ROIs) were outlined for the brain tissues of the rats and quantitative analysis was performed using the ASIPro image processing software. The imaging and quantitative analysis results are shown in Figure 14 . The uptake of the region of interest (ROI) was expressed as the percentage of the injected dose per cubic centimeter (%ID / mL).

[0123] Experiment 3: MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin that can selectively damage dopaminergic neurons and is widely used in research models of Parkinson's disease. MPTP prepared with physiological saline (injection concentration 5 mg / mL, injection dose 30 mg / kg / day) was injected intraperitoneally into C57BL / 6 mice (male, 8 - 10 weeks old, purchased from Cavens) to establish a mouse model of Parkinson's disease. The control group was injected intraperitoneally with physiological saline. Seven days after the injection of MPTP, 18 F]HYAS or 18[[F]]HYAT (5.55 MBq, 200 μL) was injected into mice via the tail vein. After the injection, dynamic PET imaging of the mouse head was performed for 1 hour on a small animal PET scanner (Siemens Inveon, Germany). After the imaging, the region of interest (ROI) of the mouse brain tissue was delineated and quantitatively analyzed using ASIPro image processing software. The imaging and quantitative analysis results are shown in Figure 15 . The uptake of the region of interest (ROI) was expressed as the percentage of the injection dose per cubic centimeter (%ID / mL).

[0124] Experimental results: As Figure 13 shown, the tissue uptake of both tracers in the muscle injected with H2O2 was higher than that in the untreated muscle. However, 18 the difference in [[[F]]HYAS was not statistically significant. In contrast, 18 [[[F]]HYAT showed better selectivity. During the entire imaging period, the uptake ratio of the H2O2-treated muscle to the untreated muscle (H2O2 / untreated) exceeded 2 and reached a maximum ratio of 3.4 at 5 - 10 minutes after injection. Meanwhile, compared with 18 [[[F]]HYAS, 18 [[[F]]HYAT also had higher uptake in the H2O2-treated muscle. 18 The highest uptake of [[[F]]HYAT in the muscle injected with H2O2 was 3.65 ± 0.14 %ID / mL at 2.5 minutes after injection, while 18 the highest uptake of [[[F]]HYAS at 2.5 minutes after injection was only 1.05 ± 0.48 %ID / mL (c) in Figure 13 . These results indicate that 18 [[[F]]HYAT can distinguish tissues with different H2O2 concentrations in vivo.

[0125] Tracers for brain imaging should have the ability to cross the blood-brain barrier. As Figure 14 shown, 18 [[[F]]HYAS seems unable to cross the blood-brain barrier because almost no signal was detected in the brain. In contrast, 18 [[[F]]HYAT could rapidly cross the blood-brain barrier after tail vein injection. The maximum uptake was reached at 3 - 3.5 minutes after injection, which was 1.31 ± 0.06 %ID / mL, and the uptake decreased to approximately 0.51 %ID / mL at 15 minutes and remained at this level within 1 hour (b) in Figure 14 . Certain physicochemical properties of small molecules play a decisive role in their ability to cross the blood-brain barrier, including the octanol-water partition coefficient (log P), the number of hydrogen bond donors (HBD), the molecular weight (MW), and the topological polar surface area (tPSA). 18 [[[F]]HYAS and18 These parameters of F]HYAT and the suggested ranges are shown in Table 1. Compared with 18 F]HYAT, 18 F]HYAT is more in line with the suggested ranges, which can explain 18 the blood-brain barrier permeability of F]HYAT.

[0126] Since 18 F]HYAT has the ability to penetrate the blood-brain barrier, it was selected for further study. Brain PET scans were performed on C57BL / 6 mice treated with MPTP to detect endogenous 18 F]HYAT. As Figure 15 shown, in control mice, 18 the initial rate of brain uptake of F]HYAT was high, reaching a peak within the first minute and then rapidly cleared. In mice treated with MPTP, the highest brain uptake (3.63 ± 0.07% ID / mL) was reached approximately 1.5 minutes after injection. In both control mice and mice treated with MPTP, the brain uptake of 18 F]HYAT tended to stabilize approximately 5 minutes after injection. The brain uptake of mice treated with MPTP was significantly higher than that of the control group. From 1.5 to 25 minutes after injection, the brain uptake of mice treated with MPTP was more than 1.5 times higher than that of control mice. These experiments show that 18 F]HYAT can detect elevated H2O2 levels in the brain.

[0127] Table 1. 18 The physicochemical properties of F]HYAS and 18 F]HYAT

[0128]

[0129] In Table 1, for the relevant information of SuggestedRanges, please refer to the literature "J. Med. Chem. 2021, 64, 13152 - 13173.".

[0130] Obviously, the above embodiments are merely examples given for clear illustration and are not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or alterations can be made based on the above description. It is not necessary and impossible to list all the implementation manners here. And the obvious changes or alterations derived therefrom are still within the protection scope of this invention.

Claims

1. A self-fixing hydrogen peroxide imaging tracer, characterized in that, The tracer has the structure shown below: In the formula, R is 2. A method for preparing the tracer according to claim 1, characterized in that, When R is , the method includes: mixing compound 1F and dichloromethane containing trifluoroacetic acid and reacting to obtain a reaction product; mixing the reaction product and 18 F]FBA in methanol and reacting to obtain a self-fixed hydrogen peroxide imaging tracer; When R is , the method includes: mixing compound 1F and dichloromethane containing trifluoroacetic acid and reacting them to obtain a reaction product; mixing the reaction product and 18 F]FBA in methanol and reacting them to obtain a self-fixed hydrogen peroxide imaging tracer; The compound 1F has the structure shown below: The compound 2F has the structure shown below:

3. The method according to claim 2, wherein The preparation method of the compound 1F includes: mixing 4-bromo-DL-mandelic acid, N-Boc-1,6-hexanediamine, 1-hydroxybenzotriazole, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and N,N-diisopropylethylamine and reacting them to obtain the compound 1A; mixing the compound 1A and diethylaminosulfur trifluoride and reacting them to obtain the compound 1B; mixing the compound 1B, bis(pinacolato)diboron, potassium acetate, and bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex and reacting them to obtain the compound 1C; mixing the compound 1C and diethanolamine and reacting them to obtain the compound 1D; mixing the compound 1D and trifluoroacetic acid and reacting them to obtain the compound 1E; mixing the compound 1E, (tert-butoxycarbonyl-aminooxy)acetic acid, 1-hydroxybenzotriazole, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and N,N-diisopropylethylamine and reacting them to obtain the compound 1F; The compound 1A has the structure shown below: The compound 1B has the structure shown below: The compound 1C has the structure shown below: The compound 1D has the structure shown below: The compound 1E has the structure shown below:

4. The method according to claim 2, wherein The preparation method of the compound 2F includes: mixing N-(3-bromopropyl)phthalimide, N-Boc-hydroxylamine, and 1,8-diazabicyclo[5.4.0]undec-7-ene and reacting them to obtain the compound 2A; mixing the compound 2A and hydrazine hydrate and reacting them to obtain the compound 2B; mixing the compound 2B, 4-bromo-DL-mandelic acid, 1-hydroxybenzotriazole, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and N,N-diisopropylethylamine and reacting them to obtain the compound 2C; mixing the compound 2C and diethylaminosulfur trifluoride and reacting them to obtain the compound 2D; mixing the compound 2D, potassium acetate, and bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex and reacting them to obtain the compound 2E; mixing the compound 2E and diethanolamine and reacting them to obtain the compound 2F; The compound 2A has the structure shown below: The compound 2B has the structure shown below: The compound 2C has the structure shown below: The compound 2D has the structure shown below: The compound 2E has the structure shown below:

5. Use of the tracer according to claim 1 in the preparation of a hydrogen peroxide imaging agent or a product for detecting diseases, characterized in that, The diseases include neurodegenerative diseases, tumors, arthritis, and / or cardiovascular and cerebrovascular diseases.

6. The application according to claim 5, wherein The neurodegenerative diseases include Alzheimer's disease and / or Parkinson's disease.

7. The application according to claim 5 or 6, characterized in that The product is a detection kit.

8. A hydrogen peroxide imaging agent, characterized in that, The components of the imaging agent include the tracer described in claim 1.

9. A product for detecting a disease, characterized in that, The components of the product include the tracer described in claim 1; the diseases include neurodegenerative diseases, tumors, arthritis, and / or cardiovascular and cerebrovascular diseases.

10. The product according to claim 9, wherein, The neurodegenerative diseases include Alzheimer's disease and / or Parkinson's disease.

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