Application of near-infrared fluorescent probe of targeted folate receptor in preparation of near-infrared first region and near-infrared second region diagnostic drugs

Abstract

The invention provides application of a near-infrared fluorescent probe of a targeted folate receptor in preparation of a near-infrared first region and near-infrared second region diagnostic drug, and relates to the technical field of organic fluorescent molecules. The folate receptor-targeted near-infrared fluorescent probe has a structural formula as shown in a formula I which is described in the specification. The near-infrared fluorescent probe provided by the invention has good tumor targeting capability and water solubility, also has near-infrared two-region developing capability, and has huge development potential and application prospect in fluorescence-guided intraoperative navigation. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the technical field of organic fluorescent molecules, and in particular to the application of a near-infrared fluorescent probe targeting folate receptors in the preparation of diagnostic drugs in the first near-infrared region and the second near-infrared region. Background Art

[0002] Cancer seriously threatens human life and health. With the deepening of population aging and the change of people's lifestyles, the challenges brought by cancer are becoming increasingly severe. Therefore, the early diagnosis and treatment of cancer have become increasingly important. With the continuous progress of technology, various advanced medical devices such as diagnostic computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), ultrasound (US), and near-infrared (NIR) fluorescence imaging have been continuously developed, which can effectively improve the detection rate of cancer and assist in resection. In particular, near-infrared fluorescence imaging provides high-resolution images of tissues and organs, has the advantages of low biotoxicity and low autofluorescence, which is conducive to minimizing background interference to the greatest extent; in addition, compared with near-infrared first-region imaging, near-infrared second-region imaging has lower background fluorescence and deeper penetration depth. Therefore, there is an urgent need to develop a fluorescent probe that can be imaged in both the first and second near-infrared regions, and it is expected that the near-infrared second-region imaging has a higher background ratio compared with the first region.

[0003] The main folate receptors are folate receptor α and folate receptor β, which are of great significance in cell growth, proliferation, etc. In tumor tissues, folate receptor α has varying degrees of overexpression, especially in ovarian cancer, non-small cell lung cancer, endometrial cancer, breast cancer, etc. Folate receptor β is mainly overexpressed in inflammatory factors such as macrophages. Therefore, designing a specific binding targeting probe for folate receptors is of great significance, which can more effectively achieve tumor imaging and improve tumor detection and resection.

[0004] CN117159552A discloses the application of peitai cyanine green in the preparation of inhibitors for subcutaneous xenografts of ovarian cancer and / or cervical cancer. The present invention provides the application of peitai cyanine green in the preparation of inhibitors for subcutaneous xenografts of human ovarian clear cell carcinoma cells, human ovarian adenocarcinoma cells, human cervical squamous carcinoma cells, and human cervical carcinoma cells. The near-infrared fluorescent probe targeting folate receptors shown in formula I of the present invention has a certain inhibitory effect on subcutaneous xenografts of SK-OV-3 cells, and during the administration of the near-infrared fluorescent probe targeting folate receptors shown in formula I, the body weight of the recipient does not change significantly, and there are no significant differences in the organ coefficients of organs such as the liver, spleen, lung, and kidney.

[0005] In view of this, the present invention is specifically proposed. Summary of the Invention

[0006] The present invention aims to provide an application of a near-infrared fluorescence probe targeting folate receptor in the preparation of diagnostic drugs in the first near-infrared region and the second near-infrared region. The near-infrared fluorescence probe targeting folate receptor can be used in fields such as urinary tract imaging and / or fluorescence-guided surgery for tumors in the first and second near-infrared regions.

[0007] In order to achieve the above object of the present invention, the following technical solutions are specifically adopted:

[0008] The present invention provides an application of a near-infrared fluorescence probe targeting folate receptor in the preparation of diagnostic drugs in the first near-infrared region and the second near-infrared region. The structural formula of the near-infrared fluorescence probe targeting folate receptor is shown as the following formula I:

[0009]

[0010] Further, the wavelength of the first near-infrared region is 700 - 900 nm, and the wavelength of the second near-infrared region is 1000 - 1700 nm.

[0011] Further, the diagnostic drugs in the first near-infrared region and the second near-infrared region include tumor imaging drugs in the first near-infrared region and the second near-infrared region.

[0012] Further, the tumor imaging drug is an ovarian cancer imaging drug.

[0013] Further, the tumor imaging drug includes ovarian cancer cell imaging drugs, and the ovarian cancer cells include any one of IGROV-1, SKOV3, OVCAR3, or OV90.

[0014] Further, the diagnostic drugs in the first near-infrared region and the second near-infrared region include urinary tract imaging drugs in the first near-infrared region and the second near-infrared region.

[0015] Further, the urinary tract imaging drug is a ureter imaging drug.

[0016] Further, the administration method of the near-infrared fluorescence probe targeting folate receptor is intravenous injection.

[0017] Further, the intravenous injection concentration of the near-infrared fluorescence probe targeting folate receptor is 0.1 - 1 nmol / μL, and imaging occurs 12 - 48 h after administration.

[0018] Further, the background ratio of the near-infrared fluorescence probe targeting folate receptor in tumors or the urinary tract in the second near-infrared region > the background ratio of the near-infrared fluorescence probe targeting folate receptor in tumors or the urinary tract in the first near-infrared region.

[0019] Further, the background ratio of the near-infrared fluorescence probe targeting folate receptor in tumors or the urinary tract in the second near-infrared region is 2.06 - 2.36.

[0020] Furthermore, the background ratio of the near-infrared fluorescence probe targeting folate receptor in tumors or urinary tracts in the first near-infrared region is 1.72 - 1.87.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] (1) The present invention provides an application of a near-infrared fluorescence probe targeting folate receptor in the preparation of diagnostic drugs in the first near-infrared region and the second near-infrared region. The near-infrared fluorescence probe targeting folate receptor shown in Formula I provided by the present invention has good tumor imaging ability in the first and second near-infrared regions in tumor-bearing mice with ovarian cancer (IGROV-1, SKOV3, OVCAR3, OV90), and has potential development and application prospects for near-infrared fluorescence imaging in the second near-infrared region. Meanwhile, the near-infrared fluorescence probe targeting folate receptor shown in Formula I provided by the present invention has good imaging effect in aspects such as ureter positioning.

[0023] (2) The background ratio of the near-infrared fluorescence probe targeting folate receptor shown in Formula I provided by the present invention in tumors or urinary tracts in the second near-infrared region > the background ratio of the near-infrared fluorescence probe targeting folate receptor in tumors or urinary tracts in the first near-infrared region, and compared with near-infrared imaging in the first near-infrared region, near-infrared imaging in the second near-infrared region has lower background fluorescence and deeper penetration depth. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required for the description of the specific embodiments or the prior art. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0025] Figure 1 Are the near-infrared fluorescence detection results of the near-infrared fluorescence probe targeting folate receptor shown in Formula I and indocyanine green (ICG) glucose injection in the second near-infrared region respectively.

[0026] Figure 2 Are the in vivo imaging results of the near-infrared fluorescence probe targeting folate receptor shown in Formula I in the first and second near-infrared regions in tumor-bearing mice with ovarian cancer IGROV-1.

[0027] Figure 3 Are the in vivo imaging results of the near-infrared fluorescence probe targeting folate receptor shown in Formula I in the first and second near-infrared regions in tumor-bearing mice with ovarian cancer SKOV3.

[0028] Figure 4 Are the in vivo imaging results of the near-infrared fluorescence probe targeting folate receptor shown in Formula I in the first and second near-infrared regions in tumor-bearing mice with ovarian cancer OV90.

[0029] Figure 5 In vivo imaging results in the first and second near-infrared regions of a near-infrared fluorescent probe targeting folate receptor shown in Formula I in OVCAR3 tumor-bearing mice with ovarian cancer.

[0030] Figure 6 In vivo imaging results of the ureter imaging of a near-infrared fluorescent probe targeting folate receptor shown in Formula I in New Zealand rabbits.

[0031] Figure 7 In vivo imaging results in the first and second near-infrared regions of a near-infrared fluorescent probe targeting folate receptor shown in Formula I in the ureter of New Zealand rabbits. Detailed implementation manners

[0032] Unless otherwise defined herein, scientific and technical terms used in conjunction with the present invention shall have the meanings commonly understood by those of ordinary skill in the art. The meanings and scopes of the terms should be clear. However, in any case of potential ambiguity, the definitions provided herein shall prevail over any dictionary or extrinsic definition. In this application, unless otherwise specified, the use of "or" means "and / or". In addition, the use of the term "comprising" and other forms is non-restrictive.

[0033] It should be noted that specific details are set forth in the following description to facilitate a thorough understanding of the present invention. However, the present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar generalizations without departing from the connotation of the present invention. Therefore, the present invention is not limited by the specific implementation manners disclosed below.

[0034] The technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0035] In a first aspect, the present invention provides an application of a near-infrared fluorescent probe targeting folate receptor in the preparation of diagnostic drugs in the first and second near-infrared regions, and the structural formula of the near-infrared fluorescent probe targeting folate receptor is shown as Formula I below:

[0036]

[0037] The present invention provides an application of a near-infrared fluorescent probe targeting folate receptor in the preparation of diagnostic drugs in the first near-infrared region and the second near-infrared region. The near-infrared fluorescent probe described in the present invention can actively target folate receptor, has tumor-specific targeting ability, good in vivo metabolic characteristics, and long tumor retention time. It can not only be applied to the preparation of fluorescent contrast agents or tumor diagnostic drugs in the first and second near-infrared regions, but also has application potential in the fields such as fluorescence-guided tumor surgical resection during clinical surgery. At the same time, the near-infrared fluorescent probe described in the present invention has good in vivo metabolic characteristics, is excreted from the body through the kidney in the form of urine after entering the body, has good potential for ureter imaging, can be applied to the preparation of urogram contrast agents or diagnostic drugs, and has application potential in the fields such as ureter positioning or protection in the clinical fields of gynecology, urology, etc.

[0038] As an alternative embodiment, the wavelength of the first near-infrared region is 650 - 900 nm, and the wavelength of the second near-infrared region is 1000 - 1700 nm.

[0039] As an alternative embodiment, the diagnostic drugs in the first near-infrared region and the second near-infrared region include tumor imaging drugs in the first near-infrared region and the second near-infrared region.

[0040] As an alternative embodiment, the tumor imaging drug is an ovarian cancer imaging drug.

[0041] As an alternative embodiment, the tumor imaging drug includes ovarian cancer cell imaging drugs, and the ovarian cancer cells include any one of IGROV-1, SKOV3, OVCAR3 or OV90.

[0042] As an alternative embodiment, the diagnostic drugs in the first near-infrared region and the second near-infrared region include urogram imaging drugs in the first near-infrared region and the second near-infrared region.

[0043] As an alternative embodiment, the urogram imaging drug is a ureter imaging drug.

[0044] As an alternative embodiment, the administration method of the near-infrared fluorescent probe targeting folate receptor is intravenous injection.

[0045] As an alternative embodiment, the intravenous injection concentration of the near-infrared fluorescent probe targeting folate receptor is 0.1 - 1 nmol / μL, and imaging occurs 12 - 48 h after administration.

[0046] As an alternative embodiment, the intravenous injection concentration of the near-infrared fluorescent probe targeting folate receptor is 0.1-1 nmol / μL, and can be, for example, 0.1 nmol / μL, 0.2 nmol / μL, 0.3 nmol / μL, 0.4 nmol / μL, 0.5 nmol / μL, 0.6 nmol / μL, 0.7 nmol / μL, 0.8 nmol / μL, 0.9 nmol / μL, 1 nmol / μL, etc.

[0047] As an alternative embodiment, the imaging time after administration of the near-infrared fluorescent probe targeting folate receptor is 12-48 h, and can be, for example, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 24 h, 26 h, 28 h, 30 h, 32 h, 34 h, 36 h, 38 h, 40 h, 42 h, 44 h, 46 h, 48 h, etc.

[0048] As an alternative embodiment, the background ratio of the near-infrared fluorescent probe targeting folate receptor in tumors or urinary tracts in the second near-infrared region > the background ratio of the near-infrared fluorescent probe targeting folate receptor in tumors or urinary tracts in the first near-infrared region.

[0049] As an alternative embodiment, the background ratio of the near-infrared fluorescent probe targeting folate receptor in tumors or urinary tracts in the second near-infrared region is 2.06-2.36.

[0050] As an alternative embodiment, the background ratio of the near-infrared fluorescent probe targeting folate receptor in tumors or urinary tracts in the first near-infrared region is 1.72-1.87.

[0051] The present invention will be further described below by way of examples. Unless otherwise specified, the materials in the examples are prepared according to existing methods or directly purchased from the market.

[0052] Structural formulas of each test sample in the following examples:

[0053] As shown in Formula I

[0054]

[0055] Example 1

[0056] This example provides near-infrared second-region fluorescence detection of the near-infrared fluorescent probe targeting folate receptor shown in Formula I and indocyanine green (ICG).

[0057] Detection method: Using 5% glucose injection, the near-infrared fluorescent probe targeting folate receptor shown in Formula I and ICG were configured into a solution with a concentration of 10 nmol / 100 μL. Detection was performed using a small animal in vivo drug screening system (Suzhou Yingrui Optoelectronic Technology Co., Ltd., Dali-IGS-600). The instrument parameters were: filter LP1000, power 10 W, exposure time 50 MS.

[0058] The detection results are as Figure 1 shown. Under the conditions of this experiment, compared with ICG, the near-infrared fluorescent probe targeting folate receptor shown in Formula I has higher near-infrared second-region luminescence efficiency and better application potential for near-infrared second-region imaging.

[0059] Example 2

[0060] This example provides in vivo imaging detection of the near-infrared fluorescent probe targeting folate receptor shown in Formula I in subcutaneous tumor-bearing IGROV-1 mice (human ovarian cancer cells).

[0061] Detection method: In a subcutaneous tumor-bearing IGROV-1 mouse model, the near-infrared fluorescent probe targeting folate receptor shown in Formula I (10 nmol / mouse, 100 μL of glucose injection) was administered via the tail vein. 24 hours after administration, near-infrared first-region and second-region fluorescence imaging were performed using a small animal in vivo imaging system (model: 3D Specturm) and a small animal in vivo drug screening system (Suzhou Yingrui Optoelectronic Technology Co., Ltd., Dali-IGS-600), respectively.

[0062] The detection results are as Figure 2 shown. Under the conditions of this experiment, the near-infrared fluorescent probe targeting folate receptor shown in Formula I in subcutaneous tumor-bearing IGROV-1 mice has good tumor targeting ability and near-infrared first-region and second-region imaging ability. The calculation results show that near-infrared second-region imaging has a higher tumor-to-background ratio compared with near-infrared first-region (TBR: 2.06 (second region) VS 1.72 (first region)). Thus, it can be seen that the near-infrared fluorescent probe targeting folate receptor shown in Formula I has good ovarian cancer imaging ability and has near-infrared second-region clinical application prospects and application potential.

[0063] Example 3

[0064] This example provides near-infrared first-region and second-region in vivo imaging of the near-infrared fluorescent probe targeting folate receptor shown in Formula I in subcutaneous tumor-bearing SKOV3 mice (human ovarian cancer cells).

[0065] Detection method: In a subcutaneous tumor SKOV3-bearing mouse model, the near-infrared fluorescence probe targeting folate receptor shown in Formula I was administered via the tail vein (10 nmol / mouse, 100 μL of glucose injection). After 24 hours of administration, fluorescence imaging in the first near-infrared region and the second near-infrared region was performed using a small animal in vivo imaging system (model: 3D Specturm) and a small animal in vivo drug screening system (Suzhou Yingrui Optoelectronic Technology Co., Ltd., Dali-IGS-600), respectively.

[0066] The detection results are as Figure 3 shown. Under the conditions of this experiment, in subcutaneous tumor SKOV3-bearing mice, the near-infrared fluorescence probe targeting folate receptor shown in Formula I had obvious tumor fluorescence signals, with good tumor targeting ability and good fluorescence imaging ability in the first near-infrared region and the second near-infrared region. The calculation results showed that the second near-infrared imaging had a higher tumor background ratio compared with the first near-infrared region (TBR: 2.15 (second region) VS 1.81 (first region)), that is, the near-infrared fluorescence probe targeting folate receptor shown in Formula I had good ovarian cancer imaging ability and had clinical application prospects and application potential in the second near-infrared region.

[0067] Example 4

[0068] This example provides the near-infrared fluorescence probe targeting folate receptor shown in Formula I for in vivo imaging in the first near-infrared region and the second near-infrared region of subcutaneous tumor OV90-bearing mice (human ovarian cancer cells).

[0069] Detection method: In a subcutaneous tumor OV90-bearing mouse model, the near-infrared fluorescence probe targeting folate receptor shown in Formula I was administered via the tail vein (10 nmol / mouse, 100 μL of glucose injection). After 24 hours of administration, fluorescence imaging in the first near-infrared region and the second near-infrared region was performed using a small animal in vivo imaging system (model: 3D Specturm) and a small animal in vivo drug screening system (Suzhou Yingrui Optoelectronic Technology Co., Ltd., Dali-IGS-600), respectively.

[0070] The detection results are as Figure 4 shown. Under the conditions of this experiment, in subcutaneous tumor OV90-bearing mice, the near-infrared fluorescence probe targeting folate receptor shown in Formula I had good tumor targeting ability and good fluorescence imaging ability in the first near-infrared region and the second near-infrared region. The calculation results showed that the second near-infrared imaging had a higher tumor background ratio compared with the first near-infrared region (TBR: 2.35 (second region) VS 1.87 (first region)), that is, the near-infrared fluorescence probe targeting folate receptor shown in Formula I had good ovarian cancer imaging ability and had clinical application prospects and application potential in the second near-infrared region.

[0071] Example 5

[0072] This example provides in vivo imaging in the near-infrared regions I and II of nude mice bearing subcutaneous tumors of OVCAR3 (human ovarian cancer cells) using the near-infrared fluorescent probe targeting folate receptor shown in Formula I.

[0073] Detection method: In a nude mouse model bearing subcutaneous tumors of OVCAR3, the near-infrared fluorescent probe targeting folate receptor shown in Formula I (10 nmol / animal, 100 μL of glucose injection solution) was administered via the tail vein. After 24 hours of administration, near-infrared imaging in region I and near-infrared imaging in region II were respectively performed using a surgical fluorescence imaging system (Nanjing Nuoyuan Medical Instrument Co., Ltd., 10B) and a small animal in vivo drug screening system (Suzhou Yingrui Optoelectronic Technology Co., Ltd., Dali-IGS-600).

[0074] The detection results are as Figure 5 shown. Under the experimental conditions of this study, in nude mice bearing subcutaneous tumors of OVCAR3, the near-infrared fluorescent probe targeting folate receptor shown in Formula I has good tumor targeting ability and good near-infrared fluorescence imaging ability in regions I and II. The calculated results show that the near-infrared imaging in region II has a higher tumor-to-background ratio (TBR: 2.24 (region II) vs 1.78 (region I)) compared to region I, that is, the near-infrared fluorescent probe targeting folate receptor shown in Formula I has good imaging ability for ovarian cancer and has the potential for clinical application in the near-infrared region II.

[0075] Example 6

[0076] This example provides in vivo imaging of the ureters of healthy New Zealand rabbits using the near-infrared fluorescent probe targeting folate receptor shown in Formula I.

[0077] Detection method: In healthy New Zealand rabbits, after anesthesia with sodium pentobarbital, the abdomen of the rabbit was dissected to expose the kidneys and bladder. After the intestines were dissected to one side, the near-infrared fluorescent probe targeting folate receptor shown in Formula I was administered via the marginal ear vein (10 nmol / animal, 1 mL of glucose injection solution). After administration, approximately 50 mL of glucose injection solution was further infused via the marginal ear vein, and fluorescence imaging was performed using a surgical fluorescence imaging system (Nanjing Nuoyuan Medical Instrument Co., Ltd., 10B).

[0078] The detection results are as Figure 6As shown, in normal rabbits, after administration of the near-infrared fluorescent probe targeting folate receptor shown in Formula I, obvious fluorescent signals appeared in the ureter region. As urine was excreted from the kidneys, obvious fluorescent signals intermittently appeared in the ureter region. After further ligating the ureter, the blocked site could be clearly observed, which helped clinicians to inspect and locate the blocked site during the operation, shortening the screening time for the lesion. At the same time, it could also help clinicians to locate the ureter in real time during the operation, avoiding accidental injury to the ureter during the operation. That is, the near-infrared fluorescent probe targeting folate receptor shown in Formula I has potential clinical application prospects and application potential in ureter imaging, with the expectation of being applied to intraoperative ureter localization and protection.

[0079] The detection results are as Figure 7 shown. The near-infrared fluorescent probe targeting folate receptor shown in Formula I has good near-infrared region I and region II fluorescence imaging capabilities in in vivo ureter imaging. The calculation results show that the near-infrared region II imaging has a higher tumor-to-background ratio (TBR: 2.36 (region II) VS 1.76 (region I)) compared with region I. That is, the near-infrared fluorescent probe targeting folate receptor shown in Formula I has good ureter imaging capabilities, has near-infrared region II clinical application prospects and application potential, and is applied to clinical ureter localization and visualization, effectively avoiding accidental injury to the ureter during the operation and improving the success rate of the operation and the postoperative quality of life of patients.

[0080] In summary, the present invention also provides an application of a near-infrared fluorescent probe targeting folate receptor in the preparation of diagnostic drugs, including applications in urinary tract imaging and near-infrared region I and region II tumor imaging. This near-infrared fluorescent probe has good tumor targeting ability and water solubility. The fluorescent probe also has the imaging ability in near-infrared region II and has great development potential and application prospects in fluorescence-guided intraoperative navigation.

[0081] Finally, it should be noted that: the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. Use of a near-infrared fluorescent probe targeting folate receptor in the preparation of diagnostic drugs in the first near-infrared region and the second near-infrared region, characterized in that, The structural formula of the near-infrared fluorescent probe targeting folate receptor is shown as Formula I below:

2. The application according to claim 1, wherein The wavelength of the first near-infrared region is 700 - 900 nm, and the wavelength of the second near-infrared region is 1000 - 1700 nm.

3. The application according to claim 1, characterized in that, The diagnostic drugs in the first near-infrared region and the second near-infrared region include tumor imaging drugs in the first near-infrared region and the second near-infrared region.

4. The application according to claim 3, characterized in that The tumor imaging drug is an ovarian cancer imaging drug.

5. The application according to claim 3 or 4, characterized in that, The tumor imaging drug includes ovarian cancer cell imaging drugs; among them, the ovarian cancer cells include any one of IGROV-1, SKOV3, OVCAR3, or OV90.

6. The application according to claim 1, characterized in that, The diagnostic drugs in the first near-infrared region and the second near-infrared region include urinary tract imaging drugs in the first near-infrared region and the second near-infrared region.

7. The application according to claim 6, wherein The urinary tract imaging drug is a ureter imaging drug.

8. The application according to claim 1, wherein The administration method of the near-infrared fluorescent probe targeting folate receptor is intravenous injection; Among them, the intravenous injection concentration of the near-infrared fluorescent probe targeting folate receptor is 0.1 - 1 nmol / μL, and imaging occurs 12 - 48 h after administration.

9. The application according to claim 1, wherein The background ratio of the near-infrared fluorescent probe targeting folate receptor in tumors or the urinary tract in the second near-infrared region > the background ratio of the near-infrared fluorescent probe targeting folate receptor in tumors or the urinary tract in the first near-infrared region.

10. The application according to claim 1, characterized in that The background ratio of the near-infrared fluorescent probe targeting folate receptor in tumors or the urinary tract in the second near-infrared region is 2.06 - 2.36; And / or, the background ratio of the near-infrared fluorescent probe targeting folate receptor in tumors or the urinary tract in the first near-infrared region is 1.72 - 1.87.

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