Tumor affinity peptide and application thereof

Abstract

The application discloses a tumor affinity peptide and application thereof. The tumor affinity peptide is a high-affinity polypeptide simulating FAP (fibroblast activation protein), and can be used for targeting fibroblast activation protein (FAP). An M label is connected to the amino acid N terminal of the tumor affinity peptide, so that a modified polypeptide is obtained. The tumor affinity peptide and the modified polypeptide can be used for preparing a tumor diagnosis reagent, a fluorescent imaging reagent or a radioactive imaging reagent of a tumor, and a tumor-targeting drug carrier.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to a tumor affinity peptide and its applications. Background Technology

[0002] Cancer threatens human health, and its mortality rate continues to rise. Early detection of malignant lesions before they metastasize to other organs allows for timely and targeted local treatment, resulting in extremely high survival rates. Therefore, early diagnosis and treatment of malignant tumors are crucial.

[0003] For tumors, conventional imaging diagnostic techniques mainly include ultrasound, CT, and MRI. These imaging diagnostic techniques achieve diagnostic results by displaying functional changes in tissues and have good application value, but they still have certain shortcomings in differential diagnosis, systemic staging, and early efficacy evaluation.

[0004] In recent years, with the deepening understanding and research of tumors and related disciplines, the focus of research has shifted to specific tumor diagnostic drugs targeting abnormally expressed targets within tumor cells for early tumor diagnosis. Target-specific tumor diagnostic drugs primarily bind specifically to tumor cells, without binding to normal cells, thus achieving highly selective and low-toxicity diagnostic effects. Currently, targeted peptides are considered a relatively ideal means of tumor targeted therapy, possessing the following advantages: 1) rapid plasma clearance, high affinity, and strong specificity; 2) good tissue penetration, enabling uptake by tumor cells; 3) easy chemical synthesis and low immunogenicity, avoiding the shortcomings of monoclonal antibody therapy.

[0005] The complex interactions and signal regulation between tumor cells and the tumor microenvironment play a crucial role in tumorigenesis and development. Fibroblasts in the tumor microenvironment, upon activation, become carcinoma-associated fibroblasts (CAFs). One characteristic that distinguishes CAFs from ordinary fibroblasts is their high expression of fibroblast activation protein (FAP). FAP is a type II transmembrane serine protease belonging to the prolyl oligopeptidase family, primarily located on the cell membrane. Its cytoplasmic, transmembrane, and extracellular structures are composed of 6, 18, and 736 amino acids, respectively. Common forms include a 95 kDa monomeric form or a 170 kDa homodimer. This homodimer consists of two molecules with identical enzymatic activity and a molecular weight of 97 × 10⁻⁶. 3The subunit composition of FAP is as follows. As a major member of the dipeptidyl peptidase family, FAP not only shares the same domain as DPP4, but also shares 48% of its amino acids in its complete amino acid sequence. The subunit composition of FAP includes a β-helical domain and an α / β hydrolysis catalytic domain. The catalytic triad composed of Ser624, Asp702, and His734 is located at the interface between the β-helical domain and the α / β hydrolysis catalytic domain, with eight β-propeller blades located at the top of the catalytic triad, serving as the inlet and outlet for selectively filtering proteins.

[0006] CAFs (cellular adenocarcinoma cells) play a crucial role in regulating the dynamic and symbiotic network among malignant epithelial cells, the extracellular matrix, and numerous non-tumor cells (such as endothelial cells, adipocytes, inflammatory cells, and immune cells), participating in processes such as tumorigenesis, progression, angiogenesis, immune regulation, signal transduction, drug resistance, and metastasis. Fibroblasts (FAPs), as a specific biomarker of CAFs, are highly expressed in the matrix of CAFs in over 90% of epithelial-derived malignant tumors (such as breast cancer, colon cancer, skin cancer, pancreatic cancer, ovarian cancer, myeloma, soft tissue cancer, and bone-derived sarcomas), while fibroblasts in normal tissues show little or no FAP expression. Therefore, FAP, as a potential biomarker and specific tumor therapeutic target, has been studied in various oncological diseases. Summary of the Invention

[0007] Purpose of the Invention: The purpose of this invention is to provide a tumor affinity peptide and its applications. The tumor affinity peptide can target human fibroblast activating protein (FAP), enabling in vivo diagnosis of tumors with high FAP receptor expression, and can be used to prepare novel targeted drug carriers.

[0008] Technical solution: The objective of this invention is achieved through the following technical solution:

[0009] This invention provides a tumor affinity peptide, the amino acid sequence of which is shown in one of SEQ ID No. 1 to 4:

[0010] SEQ ID No.1:Ser-Met-Val-Gly-Pro-Ser-Gln-Gly-Arg-Ser;

[0011] SEQ ID No.2: Thr-Gly-Pro-Gly-Pro-Asn-Gln-Cys;

[0012] SEQ ID No.3: Ser-Gly-Pro-Gly-Pro-Asn-Gln-Cys;

[0013] SEQ ID No. 4: Gly-Gly-Pro-Gly-Pro-Asn-Gln-Cys.

[0014] The aforementioned tumor affinity peptides can target human fibroblast activating protein (FAP).

[0015] This invention also provides the application of the above-mentioned tumor affinity peptide in the preparation of tumor diagnostic reagents. Preferably, it is used in the preparation of tumor diagnostic imaging agents.

[0016] This invention also provides the application of the above-mentioned tumor affinity peptide in the preparation of fluorescent imaging reagents or radioactive imaging reagents for tumors. Preferably, it is used in the preparation of tumor diagnostic imaging agents and radionuclide imaging reagents for precise localization of tumor boundaries and intraoperative image navigation.

[0017] This invention also provides the application of the above-mentioned tumor affinity peptide in the preparation of tumor-targeting drug carriers.

[0018] The tumor affinity peptide described in this invention can highly mimic the tumor targeting of FAP (fibroblast activating protein), efficiently bind to fibroblast activating protein (FAP) to the tumor site, and has good uptake and retention at the tumor site, with a high target / non-target ratio. It is suitable as a fluorescent tumor imaging agent and can be used to prepare optical imaging drugs for intraoperative tumor image navigation and precise localization of tumor boundaries.

[0019] The tumors described in this invention include, but are not limited to, breast cancer, colorectal cancer, glioma, lung cancer, and prostate cancer.

[0020] Another object of the present invention is to provide a modified polypeptide having an M-label attached to the N-terminus of the amino acid sequence of any of the above-mentioned tumor affinity peptides;

[0021] The modified polypeptide described in this invention can be represented by the general formula M-FAP-X.

[0022] Wherein, M is an optical label or a radionuclide label.

[0023] X is any integer from 1 to 4.

[0024] FAP-1 is a polypeptide with the amino acid sequence SEQ ID No. 1; FAP-2 is a polypeptide with the amino acid sequence SEQ ID No. 2; FAP-3 is a polypeptide with the amino acid sequence SEQ ID No. 3; and FAP-4 is a polypeptide with the amino acid sequence SEQ ID No. 4.

[0025] When M is optically labeled, M-FAP-X is a fluorescent molecular imaging probe with excellent imaging function. Its structure contains the present invention's polypeptide FAP-X for targeting tumors and the optically labeled M for optical imaging.

[0026] Preferably, the photolabel is selected from organic chromophores, organic fluorophores, light-absorbing compounds, light-reflecting compounds, light-scattering compounds, or bioluminescent molecules.

[0027] More preferably, the organic fluorophore is a near-infrared fluorescent dye. Even more preferably, the near-infrared fluorescent dye is ICG-Der-02(MPA), IRDye800, Cy7.5, or Cy5.5; and even more preferably, MPA.

[0028] Preferably, the radionuclide is selected from... 99m Tc, 68 Ga 64 Cu, 67 Ga 90 Y, 111 In、 177 Lu or 125 I.

[0029] The present invention also provides the use of the modified polypeptides described above in the preparation of reagents for tumor diagnosis, treatment, or tracing. Preferably, the use is in the preparation of tumor diagnostic imaging agents.

[0030] This invention also provides the use of the modified peptides in the preparation of fluorescent imaging reagents or radioactive imaging reagents for tumors. Preferably, their use is in the preparation of reagents for precise localization of tumor boundaries and intraoperative image-guided imaging, or in the preparation of radionuclide imaging reagents.

[0031] When M is fluorescently labeled, the modified polypeptide described above is a fluorescent molecular imaging probe, also known as a tumor affinity probe (fluorescent targeting probe).

[0032] Beneficial effects:

[0033] 1. This invention develops a series of novel high-affinity peptides that mimic FAP (fibroblast activating protein), which can be used to target fibroblast activating protein (FAP). Utilizing the high expression of the FAP receptor in tumors, and based on the principle of specific binding of FAP-X (X=1-4) peptides to the FAP receptor, this can be used for the early diagnosis of tumors with high FAP expression.

[0034] 2. These peptides are all low molecular weight peptides, with low synthesis costs, and they are relatively stable in vivo. By extending the half-life of the peptides, their circulation time in vivo can be increased, promoting the concentration and retention of imaging probes at the tumor site, thereby obtaining better tumor imaging results and making them more suitable for clinical application.

[0035] 3. These peptides are all reported for the first time, and the preparation methods are simple and the acquisition channels are convenient.

[0036] 4. The FAP-X (X = 1-4) series of peptides can specifically bind to tumor cells. In vivo optical imaging results have confirmed that they have excellent imaging effects on a variety of tumors, including breast cancer, colorectal cancer, and lung cancer.

[0037] 5. This invention utilizes the advantages of near-infrared fluorescent dye MPA, which has a deeper penetration depth and weaker autofluorescence in background tissue, and has good application prospects in fluorescence imaging and fluorescence-guided surgery.

[0038] 6. FAP-X (X=1-4) peptide radiopharmaceuticals can be used for tumor screening and early diagnosis, as well as for real-time non-invasive in-situ monitoring and treatment of early malignant tumors. Attached Figure Description

[0039] Figure 1 The structure of tumor affinity peptide FAP-1 is shown.

[0040] Figure 2 This is the mass spectrum of the tumor affinity peptide FAP-1.

[0041] Figure 3 This is the mass spectrum of the tumor affinity probe (fluorescent targeting probe) MPA-FAP-1.

[0042] Figure 4 The results of flow cytometry analysis were used to detect the affinity of different fluorescent targeting probes for MCF-7 cells.

[0043] Figure 5 Optical imaging of the fluorescent targeting probe MPA-FAP-1 in MCF-7 breast cancer-bearing mice.

[0044] Figure 6 Optical imaging of the fluorescent targeting probe MPA-FAP-2 in MCF-7 breast cancer-bearing mice.

[0045] Figure 7 Optical imaging of the fluorescent targeting probe MPA-FAP-3 in A549 lung cancer-bearing mice.

[0046] Figure 8 Optical imaging of the fluorescent targeting probe MPA-FAP-4 in HCT116 colorectal adenocarcinoma-bearing mice. Detailed Implementation

[0047] The technical solution of the present invention will be described in detail below through specific embodiments, but the scope of protection of the present invention is not limited to the embodiments described.

[0048] Unless otherwise specified, all reagents or instruments used in this invention are conventional products that can be purchased on the market.

[0049] The amino acids used in this invention were purchased from Jier Biochemical (Shanghai) Co., Ltd., the Rink Amide MBHA resin was purchased from Jiangsu Jitai Peptide Co., Ltd., the DMEM culture medium was purchased from Jiangsu Kaiji Biotechnology Co., Ltd., and the MCF-7 cells were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences.

[0050] Example 1: Preparation of peptide FAP-1

[0051] The amino acid sequence of FAP-1 is: Ser-Met-Val-Gly-Pro-Ser-Gln-Gly-Arg-Ser.

[0052] The polypeptide was synthesized using a solid-phase synthesis method, as detailed below:

[0053] (1) Resin swelling

[0054] Weigh 1 mmol equivalent of Rink Amide MBHA resin into a peptide synthesis tube, add enough dichloromethane (DCM) to cover the resin, and allow it to swell for 30 minutes. Remove the DCM solution, wash with DMF, and then dry.

[0055] (2) Removal of Fmoc

[0056] Add a 20% (v / v) DMF solution of piperidine to the synthesis tube, just enough to cover the resin. Deprotection time is 5 min, and this process is repeated twice. After the reaction is complete, wash with DMF.

[0057] (3) Coupling

[0058] Add 2 mmol equivalent of amino acids, 4 mmol equivalent of DIPEA, 2 mmol equivalent of HCTU and DMF to the synthesis tube, shake for 1 h, remove the reaction solution and wash with DMF, then remove Fmoc in step (2), wash, and detect ninhydrin.

[0059] (4) Add different amino acids from the sequence sequentially in the manner described in step (3) for coupling. The amino acid residues involved can be L-type or D-type. Proline (Pro) can also be replaced with hydroxyproline (Hyp), arginine (Arg) can be replaced with homo-Arg, and alanine can be replaced with β-alanine.

[0060] (5) Pyrolysis

[0061] The resin was dried with nitrogen gas. A cleavage solution (87.5% TFA + 5% anisole sulfide + 2.5% ethylenedithiol + 2.5% phenol + 2.5% water) was added to the peptide synthesis tube. The ratio of the cleavage solution volume to the resin was approximately 10 ml / g. After reacting for 2-3 hours, the solution was filtered to obtain the filtrate. A large amount of diethyl ether was added, and the mixture was centrifuged. The solid was washed three times with diethyl ether to obtain the crude peptide.

[0062] (6) Separation and purification

[0063] The peptide was purified by reversed-phase high-performance liquid chromatography (RP-HPLC) using a 10 μm reversed-phase C18 packing material. The mobile phase consisted of 0.1% TFA / water solution and acetonitrile solution, eluted using a gradient system. Quantification was performed by UV spectrophotometry to determine the UV absorbance of the peptide. The results showed that the peptide (FAP-1) was successfully synthesized (structural formula shown below). Figure 1 The purity is above 95%, and the MS results are as follows. Figure 2 As shown. The collected eluent was placed in a freeze dryer for concentration and freeze-dried into a white powder.

[0064] Example 2: Preparation of peptide FAP-X (X = 2-4)

[0065] Tumor affinity peptides FAP-2, FAP-3, and FAP-4 were prepared according to the method in Example 1.

[0066] The amino acid sequence of FAP-2 is Thr-Gly-Pro-Gly-Pro-Asn-Gln-Cys; mass spectrometry confirmed [MH]. - =772.33.

[0067] The amino acid sequence of FAP-3 is Ser-Gly-Pro-Gly-Pro-Asn-Gln-Cys; mass spectrometry confirmed [MH]. - =758.29.

[0068] The FAP-4 amino acid sequence is Gly-Gly-Pro-Gly-Pro-Asn-Gln-Cys; mass spectrometry confirmed [MH]. - =728.36.

[0069] Example 3: Preparation of the fluorescent targeting probe MPA-FAP-1

[0070] For the preparation of MPA, please refer to the inventor's previously authorized patent CN101440282.

[0071] The specific preparation method of the fluorescent targeting probe MPA-FAP-1 is as follows:

[0072] (1) Dissolve 0.02 mmol MPA in 200 μL of ultra-dry DMSO, add 3.7 mg 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 2.2 mg N-hydroxysuccinimide (EDCI / NHS) (molar ratio MPA:EDCI:NHS=1:1.5:1.5), react in the dark for 4 h to carry out the carboxyl activation reaction.

[0073] (2) Take 0.02 mmol of the solid-phase synthesized peptide FAP-1 in Example 1, 0.1 mmol of triethylamine and 200 μL of ultra-dry DMSO and add them to a 5 mL reaction flask. React for 10 min under nitrogen protection. Add the reaction solution from step (1) to the reaction solution from step (2) and stir at room temperature for 12 h.

[0074] (3) After the reaction is completed, the reaction solution is concentrated by freeze drying, then diluted with distilled water, and separated and purified by preparative liquid phase.

[0075] The preparation conditions for the liquid phase are as follows:

[0076] An Agilent 1220 Infinity II series HPLC system equipped with an Agilent ZORBAX SB-C18 semi-preparative column (9.4 × 250 mm, 5 μm) was used. Gradient elution was performed for 60 minutes at a flow rate of 2 mL / min. Mobile phase A was ultrapure water (0.01% TFA / water solution by volume), and mobile phase B was acetonitrile.

[0077] The rinsing gradient was set as follows: 95% A and 5% B for 0-5 minutes; 85% A and 15% B for 15 minutes; 70% A and 30% B for 30 minutes; 50% A and 50% B for 45 minutes; and 10% A and 90% B for 60 minutes.

[0078] The final green product was confirmed as the expected product MPA-FAP-1 by analytical HPLC and ESI-MS mass spectrometry. MS results are as follows: Figure 3 As shown.

[0079] In the above preparation process, FAP-X (X = 2, 3, 4) peptides synthesized in the solid phase are used to replace FAP-1 peptides used in the steps, thereby obtaining other peptide compounds with tumor-targeting optical imaging functions, such as MPA-FAP-2, MPA-FAP-3, and MPA-FAP-4.

[0080] Example 4: In vitro affinity experiment of fluorescent targeting probe MPA-FAP-X (X = 1-4) for MCF-7 cells

[0081] (1) First, prepare a 12-well plate. Digest the MCF-7 cells that are growing well and free from contamination. Count the cells using a counting plate. Add the same amount of cells to each well of the 12-well plate and then place it in a cell culture incubator at 37°C with 5% CO2 for 24 hours.

[0082] (2) After 24 hours of cell growth, the culture medium in the 12-well plate was discarded and 500 μL of fresh DMEM medium without serum was added. Different groups were set up: blank control group, single dye group MPA, and peptide group. 5 μL of MPA and 5 μL of MPA-FAP-X (X=1,2,3,4) fluorescent targeting probe were added respectively. The initial concentration of each group was 500 μM, and the final concentration in the well plate was 5 μM. The cells were then incubated in the incubator for 2 hours.

[0083] (3) Sample preparation before flow cytometry: Discard the old culture medium in the well plate, digest with 0.05% trypsin, resuspend in culture medium containing 10% fetal bovine serum, transfer the cell suspension to a 1.5 mL EP tube, centrifuge at 1200 rpm for 5 min, wash 3 times with 500 μL PBS buffer (pH 7.2), and finally resuspend in 500 μL PBS buffer (pH 7.2) for later use.

[0084] (4) Flow cytometry determination of cell fluorescence intensity: Set the flow cytometer parameters to medium flow rate and 40,000 cells per sample. Load the samples and measure the fluorescence intensity of each group, as well as the fluorescence intensity relative to the control group and the single dye group.

[0085] (5) Data processing: FlowJo 7.0 software was used to generate peak plots from the raw data and calculate the mean fluorescence intensity (MFI). GraphPad Prism software was used to quantitatively plot the mean fluorescence intensity and perform data difference analysis.

[0086] When the probe has a strong affinity for the receptor on the cell, the average fluorescence intensity value detected by flow cytometry is high. (See [reference needed]) Figure 4 In vitro affinity assay results showed that when the probes of MPA-FAP-X (X=1-4) at the same concentration were incubated with MCF-7 cells that expressed FAP at high concentrations, FAP-4 of the present invention had the greatest affinity for MCF-7, but FAP-1, FAP-2, and FAP-3 also had significant affinity compared with the blank control group.

[0087] Example 5: Optical imaging of the fluorescent targeting probe MPA-FAP-1 in breast cancer MCF-7 tumor-bearing mice.

[0088] The fluorescent targeting probe MPA-FAP-1 prepared in Example 3 was dissolved in physiological saline solution to prepare a solution with a concentration of 1 mg / mL. 15 μL of the MPA-FAP-1 solution was injected into three MCF-7 breast cancer-bearing nude mice (weighing approximately 20 g) via the tail vein. Optical signals were acquired at 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, and 12 h post-injection. The distribution of the MPA-FAP-1 fluorescent targeting probe in the mice and its enrichment in the tumor region were observed.

[0089] The imaging results of the fluorescent targeting probe MPA-FAP-1 in three tumor-bearing nude mice were basically consistent. The 1-hour imaging showed that the probe had significantly accumulated in the tumor, with a relatively clear tumor margin. Even at 12 hours, the probe remained embedded in the tumor. The imaging results are as follows: Figure 5 As shown in the figure, the probe was most enriched at the tumor site at 1 hour, while it was rapidly taken up and cleared in other background organs. The signal from the bladder suggests that the probe is mainly metabolized by the kidneys.

[0090] Example 6: Optical imaging of the fluorescent targeting probe MPA-FAP-2 in MCF-7 breast cancer-bearing mice.

[0091] The fluorescent targeting probe MPA-FAP-2 prepared in Example 3 was dissolved in physiological saline solution to prepare a solution with a concentration of 1 mg / mL. 15 μL of the MPA-FAP-2 solution was injected into three MCF-7 breast cancer-bearing nude mice (weighing approximately 20 g) via the tail vein. Optical signals were acquired at 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, and 12 h post-injection. The distribution of the probe in the mice and its enrichment in the tumor region were observed.

[0092] The imaging results of the fluorescent targeting probe MPA-FAP-2 in three tumor-bearing nude mice were basically consistent. The 1-hour imaging showed that the probe had significantly accumulated in the tumor, with a relatively clear tumor margin. Even at 12 hours, the probe remained in the tumor. The imaging results are as follows: Figure 6 As shown in the figure, the probe was most enriched at the tumor site at 1 hour, while it was rapidly taken up and cleared in other background organs. The signal from the bladder suggests that the probe is mainly metabolized by the kidneys.

[0093] Example 7 Optical imaging of the fluorescent targeting probe MPA-FAP-3 in A549 lung cancer tumor-bearing mice

[0094] The fluorescent targeting probe MPA-FAP-3 prepared in Example 3 was dissolved in physiological saline solution to prepare a solution with a concentration of 1 mg / mL. 15 μL of the MPA-FAP-3 solution was injected into three A549 tumor-bearing nude mice (weighing approximately 20 g) via the tail vein. Optical signals were acquired at 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, and 12 h post-injection. The distribution of the probe in the mice and its enrichment in the tumor region were observed.

[0095] The imaging results of the fluorescent targeting probe MPA-FAP-3 in three tumor-bearing nude mice were basically consistent. The 1-hour imaging showed that the probe had significantly accumulated in the tumor, with a relatively clear tumor margin. Even at 12 hours, the probe remained in the tumor. The imaging results are as follows: Figure 7 As shown in the figure, the probe was most enriched at the tumor site at 1 hour, while it was rapidly taken up and cleared in other background organs. The signal from the bladder suggests that the probe is mainly metabolized by the kidneys.

[0096] Example 8: Optical imaging of the fluorescent targeting probe MPA-FAP-4 in HCT116 colorectal adenocarcinoma-bearing mice.

[0097] The fluorescent targeting probe MPA-FAP-4 prepared in Example 3 was dissolved in physiological saline solution to prepare a solution with a concentration of 1 mg / mL. 15 μL of the MPA-FAP-4 solution was injected into three HCT116 nude mice (weighing approximately 20 g) bearing colorectal adenocarcinoma via the tail vein. Optical signals were acquired at 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, and 12 h post-injection. The distribution of the probe in the mice and its enrichment in the tumor region were observed.

[0098] The imaging results of the fluorescent targeting probe MPA-FAP-4 in three tumor-bearing nude mice were basically consistent. The 1-hour imaging showed that the probe had significantly accumulated in the tumor, with a relatively clear tumor margin. Even at 12 hours, the probe remained in the tumor. The imaging results are as follows: Figure 8 As shown in the figure, the probe accumulated most at the tumor site at 0.5 h, while it was rapidly taken up and cleared in other background organs. The signal from the bladder suggests that the probe is mainly metabolized by the kidneys.

[0099] The above pharmacodynamic experiments show that the peptides of the present invention can specifically bind to various tumor cells, preferably breast cancer, colorectal cancer, and lung cancer. The high affinity properties of the targeting peptides can be used for optical imaging of malignant tumors. These high-affinity peptide monomers, peptide dimers, or peptide multimers, directly or indirectly coupled with fluorescent dyes, can serve as tumor-specific targeting molecular probes, expected to achieve precise localization of tumor boundaries, providing real-time capabilities for preoperative and intraoperative image navigation, and improving surgical precision.

[0100] As described above, although the invention has been shown and described with reference to specific preferred embodiments, it should not be construed as limiting the invention itself. Various changes in form and detail may be made without departing from the spirit and scope of the invention as defined in the appended claims.

Claims

1. A fluorescent targeting probe, characterized in that, The fluorescent targeting probe has an MPA label attached to the N-terminus of the amino acid sequence of the tumor affinity peptide; the amino acid sequence of the tumor affinity peptide is one of SEQ ID No. 2 to 4; The MPA is the near-infrared fluorescent dye ICG-Der-02 described in CN101440282.

2. The use of the fluorescent targeting probe according to claim 1 in the preparation of reagents for tumor diagnosis or tracing, characterized in that, The tumors are breast cancer, lung cancer, and colorectal adenocarcinoma.

3. The application of the fluorescent targeting probe according to claim 1 in the preparation of fluorescent imaging reagents for tumors, characterized in that, The tumors are breast cancer, lung cancer, and colorectal adenocarcinoma.

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