Use of folate receptor-targeting near-infrared fluorescent probe in preparation of diagnostic drug for near-infrared region i and near-infrared region ii

WO2026219094A1PCT designated stage Publication Date: 2026-10-22NANJING NUOYUAN MEDICAL DEVICES CO LTD
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Patent Information

Application Number
PCT/CN2026/089873
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2025-04-16
Filing Date
2026-04-10
Publication Date
2026-10-22

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Abstract

Use of a folate receptor-targeting near-infrared fluorescent probe in the preparation of a diagnostic drug for near-infrared region I and near-infrared region II. The structural formula of the folate receptor-targeting near-infrared fluorescent probe is represented by the following formula I. The fluorescent probe exhibits good tumor targeting ability and water solubility, and also has imaging capability in the near-infrared region II, and can be used for fluorescence-guided intraoperative navigation.
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Description

Application of a near-infrared fluorescent probe targeting folate receptor in the preparation of diagnostic drugs in the near-infrared I and near-infrared II regions Technical Field

[0001] This invention relates to the field of organic fluorescent molecular technology, specifically to the application of a near-infrared fluorescent probe targeting folic acid receptors in the preparation of diagnostic drugs in the near-infrared I and near-infrared II regions. Background Technology

[0002] Cancer poses a serious threat to human life and health. With the deepening of population aging and changes in lifestyle, the challenges posed by cancer are becoming increasingly severe. Therefore, early diagnosis and treatment of cancer are becoming increasingly important. With the continuous advancement 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 are constantly developing, effectively improving the detection rate and assisting in cancer clearance. Near-infrared fluorescence imaging, in particular, provides high-resolution images of tissues and organs, with advantages such as low biotoxicity and low autofluorescence, which helps to minimize background interference. Furthermore, compared with near-infrared I imaging, near-infrared II imaging has lower background fluorescence and deeper penetration depth. Therefore, there is an urgent need to develop a fluorescent probe capable of imaging in both near-infrared I and II regions, with the expectation that its near-infrared II imaging will have a higher background contrast ratio compared to I region.

[0003] The most important folate receptors are the α-receptor and β-receptor, which play a crucial role in cell growth and proliferation. In tumor tissues, α-receptors are overexpressed to varying degrees, particularly in ovarian cancer, non-small cell lung cancer, endometrial cancer, and breast cancer. β-receptors are mainly overexpressed in inflammatory cytokines such as macrophages. Therefore, designing specific binding-targeting probes against folate receptors is of great significance, enabling more effective tumor visualization and improving tumor detection and resection.

[0004] CN117159552A discloses the application of Peptazone Green in the preparation of inhibitors for subcutaneous xenografts of ovarian cancer and / or cervical cancer. This invention provides the application of Peptazone Green in the preparation of inhibitors for human ovarian clear cell carcinoma cells, human ovarian adenocarcinoma cells, human cervical squamous cell carcinoma cells, and human cervical cancer subcutaneous xenografts. The near-infrared fluorescent probe targeting the folate receptor, as shown in Formula I of this invention, exhibits a certain inhibitory effect on subcutaneous xenografts of SK-OV-3 cells. Furthermore, the near-infrared fluorescent probe targeting the folate receptor, as shown in Formula I, shows no significant change in the recipient's body weight during administration, and no significant difference in organ coefficients for the liver, spleen, lungs, and kidneys.

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

[0006] The purpose of this invention is to provide an application of a near-infrared fluorescent probe targeting the folate receptor in the preparation of diagnostic drugs in the near-infrared I and near-infrared II regions. This near-infrared fluorescent probe targeting the folate receptor can be used in fields such as urinary tract imaging and / or near-infrared I and II region tumor fluorescence-guided surgery.

[0007] In order to achieve the above-mentioned objectives of the present invention, the following technical solution is adopted:

[0008] This invention provides the application of a near-infrared fluorescent probe targeting the folic acid receptor in the preparation of diagnostic drugs in the near-infrared I and near-infrared II regions. The structural formula of the near-infrared fluorescent probe targeting the folic acid receptor is shown in Formula I below.

[0009] Formula I:

[0010] Furthermore, the wavelength of the near-infrared region I is 700~900 nm, and the wavelength of the near-infrared region II is 1000~1700 nm.

[0011] Furthermore, the near-infrared I and near-infrared II diagnostic drugs include near-infrared I and near-infrared II tumor contrast agents.

[0012] Furthermore, the tumor contrast agent is an ovarian cancer contrast agent.

[0013] Furthermore, the tumor contrast agent includes an ovarian cancer cell contrast agent, wherein the ovarian cancer cells include any one of IGROW-1, SKOV3, OVCAR3, or OV90.

[0014] Furthermore, the near-infrared I and near-infrared II diagnostic drugs include near-infrared I and near-infrared II urinary tract imaging drugs.

[0015] Furthermore, the urinary tract contrast agent is a ureter contrast agent.

[0016] Furthermore, the near-infrared fluorescent probe targeting the folic acid receptor is administered via intravenous injection.

[0017] Furthermore, the intravenous injection concentration of the near-infrared fluorescent probe targeting the folic acid receptor is 0.1~1 nmol / μL, and the image is developed 12~48 h after administration.

[0018] Furthermore, the background ratio of the near-infrared fluorescent probe targeting the folic acid receptor in the near-infrared II region of the tumor or urinary tract is greater than that of the near-infrared fluorescent probe targeting the folic acid receptor in the near-infrared I region of the tumor or urinary tract.

[0019] Furthermore, the near-infrared fluorescent probe targeting the folic acid receptor has a background ratio of 2.06 to 2.36 in the near-infrared II region for tumors or urinary tracts.

[0020] Furthermore, the near-infrared fluorescent probe targeting the folic acid receptor has a background ratio of 1.72 to 1.87 in the near-infrared region of tumors or urinary tracts.

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

[0022] (1) This invention provides the application of a near-infrared fluorescent probe targeting the folate receptor in the preparation of near-infrared I and near-infrared II diagnostic drugs. The near-infrared fluorescent probe targeting the folate receptor shown in Formula I provided by this invention has good near-infrared I and II tumor imaging ability in ovarian cancer (IGROV-1, SKOV3, OVCAR3, OV90) tumor-bearing mice, and has potential prospects for the development and application of near-infrared II fluorescence imaging. At the same time, the near-infrared fluorescent probe targeting the folate receptor shown in Formula I provided by this invention has good imaging effect in ureter localization and other aspects.

[0023] (2) The background ratio of the near-infrared fluorescent probe targeting the folate receptor shown in Formula I provided by the present invention in the near-infrared II region of the tumor or urinary tract is greater than that of the near-infrared fluorescent probe targeting the folate receptor in the near-infrared I region of the tumor or urinary tract. Compared with the near-infrared I region imaging, the near-infrared II region imaging has lower background fluorescence and deeper penetration depth.

[0024] Attached Figure Description

[0025] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0026] Figure 1 shows the near-infrared fluorescence detection results of the near-infrared II region for the near-infrared fluorescent probe targeting the folic acid receptor shown in Formula I and the glucose injection of indocyanine green (ICG).

[0027] Figure 2 shows the in vivo imaging results of the near-infrared fluorescent probe targeting the folate receptor, as shown in Formula I, in IGROWV-1 ovarian cancer-bearing mice in the near-infrared regions I and II.

[0028] Figure 3 shows the in vivo imaging results of the near-infrared fluorescent probe targeting the folate receptor, as shown in Formula I, in SKOV3 ovarian cancer-bearing mice in the near-infrared regions I and II.

[0029] Figure 4 shows the in vivo imaging results of the near-infrared fluorescent probe targeting the folate receptor, as shown in Formula I, in OV90 ovarian cancer-bearing mice in the near-infrared regions I and II.

[0030] Figure 5 shows the in vivo imaging results of the near-infrared fluorescent probe targeting the folate receptor, as shown in Formula I, in OVCAR3 ovarian cancer-bearing mice in the near-infrared regions I and II.

[0031] Figure 6 shows the imaging results of the near-infrared fluorescent probe targeting the folic acid receptor, as shown in Formula I, in the ureter of a New Zealand rabbit.

[0032] Figure 7 shows the in vivo imaging results of the near-infrared fluorescent probe targeting the folic acid receptor, as shown in Formula I, in the near-infrared regions I and II of the ureter in a New Zealand rabbit.

[0033] Detailed Implementation

[0034] Unless otherwise defined herein, the scientific and technical terms used in conjunction with this invention shall have the meanings commonly understood by one of ordinary skill in the art. The meaning and scope of terms shall be clear; however, in any case of potential ambiguity, the definitions provided herein shall prevail over any dictionary or foreign definitions. In this application, unless otherwise stated, the use of "or" means "and / or". Furthermore, the use of the term "comprising" and other forms is non-limiting.

[0035] It should be noted that specific details are set forth in the following description to provide a full understanding of the invention. However, the invention can be practiced in many ways other than those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0036] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0037] In a first aspect, the present invention provides the application of a near-infrared fluorescent probe targeting the folic acid receptor in the preparation of diagnostic drugs in the near-infrared I and near-infrared II regions, wherein the structural formula of the near-infrared fluorescent probe targeting the folic acid receptor is shown in Formula I below:

[0038] Formula I:

[0039] This invention provides the application of a near-infrared fluorescent probe targeting folate receptors in the preparation of near-infrared I and near-infrared II diagnostic drugs. The near-infrared fluorescent probe of this invention can actively target folate receptors, exhibiting tumor-specific targeting capability, good in vivo metabolic characteristics, and long tumor retention time. It can be used not only in the preparation of near-infrared I and II fluorescent contrast agents or tumor diagnostic drugs, but also has potential applications in clinical surgical procedures such as fluorescence-guided tumor resection. Furthermore, the near-infrared fluorescent probe of this invention has good in vivo metabolic characteristics, being excreted through the kidneys in the form of urine after entering the body, exhibiting good ureteral imaging potential. It can be used in the preparation of urinary tract contrast agents or diagnostic drugs, and has potential applications in clinical fields such as gynecology and urology for ureteral localization or protection.

[0040] As an optional implementation, the wavelength of the near-infrared region I is 650~900 nm, and the wavelength of the near-infrared region II is 1000~1700 nm.

[0041] As an optional implementation, the near-infrared I and near-infrared II diagnostic drugs include near-infrared I and near-infrared II tumor imaging drugs.

[0042] As an optional implementation, the tumor contrast agent is an ovarian cancer contrast agent.

[0043] As an optional implementation, the tumor contrast agent includes an ovarian cancer cell contrast agent, wherein the ovarian cancer cells include any one of IGROW-1, SKOV3, OVCAR3, or OV90.

[0044] As an optional implementation, the near-infrared I and near-infrared II diagnostic drugs include near-infrared I and near-infrared II urinary tract imaging drugs.

[0045] As an optional implementation, the urinary tract contrast agent is a ureter contrast agent.

[0046] As an optional implementation, the near-infrared fluorescent probe targeting the folic acid receptor is administered via intravenous injection.

[0047] As an optional implementation, the intravenous injection concentration of the near-infrared fluorescent probe targeting the folic acid receptor is 0.1~1 nmol / μL, and the image is developed 12~48 h after administration.

[0048] As an optional implementation, the intravenous injection concentration of the near-infrared fluorescent probe targeting the folic acid receptor is 0.1~1 nmol / μL, for example, it can be 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.

[0049] As an optional implementation, the administration and development time of the near-infrared fluorescent probe targeting the folic acid receptor is 12-48 h, for example, it can be 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.

[0050] As an optional implementation, the background ratio of the near-infrared fluorescent probe targeting the folate receptor in the near-infrared II region of the tumor or urinary tract is greater than the background ratio of the near-infrared fluorescent probe targeting the folate receptor in the near-infrared I region of the tumor or urinary tract.

[0051] As an optional implementation, the near-infrared fluorescent probe targeting the folic acid receptor has a background ratio of 2.06 to 2.36 in the near-infrared II region of tumors or urinary tracts.

[0052] As an optional implementation, the near-infrared fluorescent probe targeting the folic acid receptor has a background ratio of 1.72 to 1.87 in the near-infrared region of tumors or urinary tracts.

[0053] The present invention will be further illustrated by the following examples. Unless otherwise specified, the materials in the examples are prepared according to existing methods or purchased directly from the market.

[0054] The following examples illustrate the structural formulas of the test samples:

[0055] As shown in Equation I:

[0056] Indocyanine Green (ICG):

[0057] Example 1

[0058] This embodiment provides a near-infrared fluorescent probe targeting the folic acid receptor as shown in Formula I and near-infrared II fluorescence detection of indocyanine green (ICG).

[0059] Detection method: The near-infrared fluorescent probe targeting the folic acid receptor shown in Formula I and ICG were prepared into a solution with a concentration of 10 nmol / 100 μL using 5% glucose injection. The solution was detected using a small animal in vivo drug screening system (Suzhou Yingrui Optical Technology Co., Ltd., Dali-IGS-600). The instrument parameters were: LP1000 filter, 10 W power, and 50 MS exposure time.

[0060] The test results are shown in Figure 1. Under the experimental conditions, compared with ICG, the near-infrared fluorescent probe targeting the folic acid receptor shown in Formula I has higher near-infrared II luminescence efficiency and better near-infrared II imaging application potential.

[0061] Example 2

[0062] This embodiment provides the in vivo imaging detection of the near-infrared fluorescent probe targeting the folate receptor as shown in Formula I in subcutaneous tumor IGROWV-1 tumor-bearing mice (human ovarian cancer cells).

[0063] Detection method: In the subcutaneous tumor IGROWV-1 tumor-bearing mouse model, the near-infrared fluorescent probe targeting the folate receptor (10 nmol / mouse, 100 μL glucose injection) of Formula I was administered via tail vein. 24 h after administration, fluorescence imaging was performed in the near-infrared I and near-infrared II regions using a small animal in vivo imaging system (model: 3D Specturm) and a small animal in vivo drug screening system (Suzhou Yingrui Optical Technology Co., Ltd., Dali-IGS-600).

[0064] The detection results are shown in Figure 2. Under the experimental conditions, the near-infrared fluorescent probe targeting the folate receptor, as shown in Formula I, exhibited good tumor targeting ability and near-infrared I and II imaging capabilities in subcutaneous tumor-bearing IGROWV-1 mice. Calculation results showed that near-infrared II imaging had a higher tumor background ratio (TBR: 2.06 (II) vs. 1.72 (I)) compared to near-infrared I imaging. Therefore, the near-infrared fluorescent probe targeting the folate receptor, as shown in Formula I, possesses good imaging ability for ovarian cancer and has promising clinical application prospects and potential in the near-infrared II region.

[0065] Example 3

[0066] This embodiment provides in vivo imaging of near-infrared regions I and II of SKOV3 tumor-bearing mice (human ovarian cancer cells) using a near-infrared fluorescent probe targeting the folate receptor as shown in Formula I.

[0067] Detection method: In the subcutaneous tumor SKOV3 tumor-bearing mouse model, the near-infrared fluorescent probe targeting the folate receptor (10 nmol / mouse, 100 μL glucose injection) of Formula I was administered via tail vein. 24 h after administration, fluorescence imaging was performed in the near-infrared I and near-infrared II regions using a small animal in vivo imaging system (model: 3D Specturm) and a small animal in vivo drug screening system (Suzhou Yingrui Optical Technology Co., Ltd., Dali-IGS-600), respectively.

[0068] The detection results are shown in Figure 3. Under the experimental conditions, in SKOV3 subcutaneous tumor-bearing mice, the near-infrared fluorescent probe targeting the folate receptor, as shown in Formula I, exhibited significant tumor fluorescence signals, demonstrating good tumor targeting ability and excellent near-infrared I and II fluorescence imaging capabilities. Calculation results showed that near-infrared II imaging had a higher tumor background ratio (TBR: 2.15 (II) vs. 1.81 (I)) compared to I, indicating that the near-infrared fluorescent probe targeting the folate receptor, as shown in Formula I, possesses good ovarian cancer imaging capabilities and demonstrates promising clinical application prospects and potential in near-infrared II imaging.

[0069] Example 4

[0070] This embodiment provides in vivo imaging of near-infrared regions I and II of subcutaneous tumor-bearing mice (human ovarian cancer cells) using a near-infrared fluorescent probe targeting the folic acid receptor as shown in Formula I.

[0071] Detection method: In the OV90 subcutaneous tumor-bearing mouse model, the near-infrared fluorescent probe targeting the folate receptor (10 nmol / mouse, 100 μL glucose injection) of Formula I was administered via tail vein. 24 h after administration, near-infrared I and near-infrared II 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 Optical Technology Co., Ltd., Dali-IGS-600), respectively.

[0072] The detection results are shown in Figure 4. Under the experimental conditions, in subcutaneous tumor-bearing OV90 mice, the near-infrared fluorescent probe targeting the folate receptor as shown in Formula I exhibited good tumor targeting ability and good near-infrared I and near-infrared II fluorescence imaging capabilities. Calculation results showed that near-infrared II imaging had a higher tumor background ratio (TBR: 2.35 (II) vs. 1.87 (I)) compared to I, indicating that the near-infrared fluorescent probe targeting the folate receptor as shown in Formula I has good ovarian cancer imaging ability and shows promising clinical application prospects and potential in the near-infrared II region.

[0073] Example 5

[0074] This embodiment provides in vivo imaging of near-infrared regions I and II of subcutaneous tumor OVCAR3 tumor-bearing mice (human ovarian cancer cells) using a near-infrared fluorescent probe targeting the folate receptor as shown in Formula I.

[0075] Detection method: In the OVCAR3 subcutaneous tumor-bearing mouse model, the near-infrared fluorescent probe targeting the folate receptor (10 nmol / mouse, 100 μL glucose injection) of Formula I was administered via tail vein. 24 h after administration, near-infrared imaging was performed in the near-infrared I and near-infrared II regions using a surgical fluorescence imaging system (Nanjing Nuoyuan Medical Instrument Co., Ltd., 10B) and a small animal in vivo drug screening system (Suzhou Yingrui Optical Technology Co., Ltd., Dali-IGS-600), respectively.

[0076] The detection results are shown in Figure 5. Under the experimental conditions, in subcutaneous OVCAR3 tumor-bearing mice, the near-infrared fluorescent probe targeting the folate receptor as shown in Formula I exhibited good tumor targeting ability and good near-infrared I and near-infrared II fluorescence imaging capabilities. Calculation results showed that near-infrared II imaging had a higher tumor background ratio (TBR: 2.24 (II) vs. 1.78 (I)) compared to I, indicating that the near-infrared fluorescent probe targeting the folate receptor as shown in Formula I has good ovarian cancer imaging ability and shows promising clinical application prospects and potential in the near-infrared II region.

[0077] Example 6

[0078] This embodiment provides in vivo imaging of the ureter of a healthy New Zealand rabbit using a near-infrared fluorescent probe targeting the folic acid receptor as shown in Formula I.

[0079] Detection method: In healthy New Zealand rabbits, after anesthesia with sodium pentobarbital, the abdomen of the rabbits was opened to expose the kidneys and bladder. After the intestines were dissected to one side, the near-infrared fluorescent probe targeting the folic acid receptor shown in Formula I was administered via the marginal ear vein (10 nmol / rabbit, 1 mL of glucose injection). After administration, about 50 mL of glucose injection was infused via the marginal ear vein. Fluorescence imaging was performed using a surgical fluorescence imaging system (Nanjing Nuoyuan Medical Instrument Co., Ltd., 10B).

[0080] The test results are shown in Figure 6. In normal rabbits, after administration of the near-infrared fluorescent probe targeting the folic acid receptor (Formula I), a significant fluorescent signal was observed in the ureter. As urine was excreted from the kidneys, the ureter showed intermittently prominent fluorescent signals. Further ligation of the ureter could clearly reveal the obstruction site, aiding clinicians in visualizing and locating the obstruction during surgery and shortening the lesion screening time. It also helps clinicians locate the ureter in real time during surgery, avoiding accidental injury. Therefore, the near-infrared fluorescent probe targeting the folic acid receptor (Formula I) has potential clinical applications in ureteral imaging, aiming for intraoperative ureteral localization and protection.

[0081] The detection results are shown in Figure 7. The near-infrared fluorescent probe targeting the folate receptor, as shown in Formula I, exhibits excellent near-infrared I and near-infrared II fluorescence imaging capabilities in ureteral in vivo imaging. Calculation results show that near-infrared II imaging has a higher tumor basal ratio (TBR: 2.36 (II) vs. 1.76 (I)) compared to II. This indicates that the near-infrared fluorescent probe targeting the folate receptor, as shown in Formula I, has good ureteral imaging capabilities and demonstrates promising clinical application prospects and potential in near-infrared II imaging. Its application in clinical ureteral localization and visualization can effectively avoid intraoperative ureteral injury, improve surgical success rates, and enhance postoperative patient quality of life.

[0082] In summary, this invention also provides the application of a near-infrared fluorescent probe targeting the folate receptor in the preparation of diagnostic drugs, including its application in urinary tract imaging and near-infrared I and II region tumor imaging. This near-infrared fluorescent probe has good tumor targeting ability and water solubility, and it also has near-infrared II region imaging capability, showing great development potential and application prospects in fluorescence-guided navigation.

[0083] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. The application of a near-infrared fluorescent probe targeting the folic acid receptor in the preparation of diagnostic drugs in the near-infrared I and near-infrared II regions, characterized in that, The structural formula of the near-infrared fluorescent probe targeting the folic acid receptor is shown in Formula I below: Formula I: 。 2. The application according to claim 1, characterized in that, The wavelength of the near-infrared region I is 700~900 nm, and the wavelength of the near-infrared region II is 1000~1700 nm.

3. The application according to claim 1, characterized in that, The near-infrared I and near-infrared II diagnostic drugs include near-infrared I and near-infrared II tumor imaging drugs.

4. The application according to claim 3, characterized in that, The tumor contrast agent is a contrast agent for ovarian cancer.

5. The application according to claim 3 or 4, characterized in that, The tumor contrast agent includes a contrast agent for ovarian cancer cells; wherein the ovarian cancer cells include any one of IGROW-1, SKOV3, OVCAR3, or OV90.

6. The application according to claim 1, characterized in that, The near-infrared I and near-infrared II diagnostic drugs include near-infrared I and near-infrared II urinary tract imaging drugs.

7. The application according to claim 6, characterized in that, The urinary tract contrast agent is a ureter contrast agent.

8. The application according to claim 1, characterized in that, The near-infrared fluorescent probe targeting the folic acid receptor is administered via intravenous injection. The intravenous injection concentration of the near-infrared fluorescent probe targeting the folic acid receptor is 0.1~1 nmol / μL, and the fluorescence is observed 12~48 h after administration.

9. The application according to claim 1, characterized in that, The background ratio of the near-infrared fluorescent probe targeting the folate receptor in the near-infrared II region of the tumor or urinary tract is greater than that of the near-infrared fluorescent probe targeting the folate receptor in the near-infrared I region of the tumor or urinary tract.

10. The application according to claim 1, characterized in that, The near-infrared fluorescent probe targeting the folic acid receptor has a background ratio of 2.06 to 2.36 in the near-infrared II region for tumors or urinary tracts. And / or, the near-infrared fluorescent probe targeting the folate receptor has a background ratio of 1.72 to 1.87 in the near-infrared region of tumors or urinary tracts.