Method for assessing rapid recurrent in-stent restenosis of a coronary artery

Abstract

The application discloses a method for evaluating rapid recurrence type coronary in-stent restenosis. The method adopts an imaging agent, the imaging agent targets fibroblast activation protein, and the imaging agent comprises a radionuclide-labeled fibroblast activation protein inhibitor for specifically binding to the fibroblast activation protein. The imaging agent for evaluating rapid recurrence type coronary in-stent restenosis provided by the application can quickly and non-invasively evaluate the risk of rapid recurrence type coronary in-stent restenosis based on an imaging technology.

Description

Technical Field

[0001] This application relates to biomedical technology, specifically to a method for evaluating rapidly recurrent in-stent restenosis of the coronary arteries. Background Technology

[0002] Among related technologies, percutaneous coronary intervention (PCI) is commonly used for coronary artery disease. PCI involves placing a coronary stent within the narrowed coronary artery, effectively relieving myocardial ischemia and improving patient prognosis. After PCI, some patients may experience in-stent restenosis, one type of which is called rapid recurrent coronary in-stent restenosis (RECUR). RECUR is defined as three or more myocardial infarctions or target vessel revascularizations within one year of stent implantation via PCI due to coronary artery stenosis. The annual incidence of RECUR is approximately 1%–2%, accounting for 5%–10% of all PCI cases. The 3-year risk of cardiac death and myocardial infarction is significantly higher in RECUR patients than in those with conventional in-stent restenosis.

[0003] Among related technologies, the average time to diagnosis of RECUR exceeds 12 months; conventional treatments have limited effectiveness for RECUR with high inflammatory burden and proliferative drive, requiring targeted anti-inflammatory therapy. Therefore, early and accurate assessment of the risk of developing RECUR is crucial. However, currently, there are no effective non-invasive imaging techniques for RECUR risk assessment. Summary of the Invention

[0004] The purpose of this application is to provide an imaging agent and method for evaluating rapidly recurrent in-stent restenosis of the coronary arteries, which can solve the technical problem that there is no effective non-invasive imaging technology for RECUR risk assessment in related technologies.

[0005] The technical solution of this application is as follows: In a first aspect, an imaging agent is provided for evaluating rapidly recurrent in-stent restenosis of the coronary artery, the imaging agent targeting and activating fibroblasts, the imaging agent comprising a radionuclide-labeled inhibitor of fibroblast activating protein, the inhibitor of fibroblast activating protein being used to specifically bind to fibroblast activating protein.

[0006] In some embodiments, the developing agent includes a fibroblast activator protein inhibitor precursor and a radionuclide, wherein the fibroblast activator protein inhibitor precursor is labeled with the radionuclide.

[0007] In some embodiments, the active structure of the fibroblast activator protein inhibitor precursor is 5-iodoquinoline-4-amide.

[0008] In some embodiments, radionuclides include 18 F, 68 Ga、 64 Cu、 99m Tc, 90 Y、 225 Ac、 125 I, 131 At least one of I.

[0009] In some embodiments, the fibroblast activator protein inhibitor precursor includes at least one of FAPI-04, FAPI-42, FAPI-34, FAPI-74, DP-FAPI, or iFAPI, and the fibroblast activator protein inhibitor precursor is coupled with a radionuclide.

[0010] In some embodiments, information on the uptake intensity of fibroblast activator protein inhibitors in the heart and coronary artery regions of subjects who have received imaging agents is positively correlated with the risk of rapid recurrent in-stent restenosis of the coronary arteries.

[0011] Secondly, it provides the use of the imaging agents described above in evaluating rapid recurrent in-stent restenosis of the coronary arteries.

[0012] Thirdly, a method for evaluating rapidly recurrent in-stent restenosis of the coronary arteries is provided, comprising the following steps: Administer an effective dose of the imaging agent as described above to the subject; Images of the subject's heart and coronary artery regions were acquired using radionuclide imaging technology; Analyze the distribution characteristics of radionuclides in the images, and assess the distribution characteristics and activation degree of fibroblast activation proteins based on the distribution characteristics; The risk of rapidly recurrent in-stent restenosis in coronary arteries is assessed based on the distribution characteristics and activation levels of fibroblast activating proteins.

[0013] In one embodiment, the distribution features include ingestion spatial distribution and ingestion intensity information.

[0014] The technical solutions provided by the embodiments of this application bring at least the following beneficial effects: The imaging agent and method provided in this application for evaluating rapidly recurrent coronary artery in-stent restenosis include a radionuclide-labeled fibroblast activator protein inhibitor. The fibroblast activator protein inhibitor is used to specifically bind to fibroblast activator protein, thereby enabling the imaging agent to target fibroblasts. The distribution characteristics of fibroblast activator protein in the subject's body are traced by radionuclide labeling, thereby generating an assessment of the risk of rapidly recurrent coronary artery in-stent restenosis based on the distribution characteristics and activation degree of fibroblast activator protein.

[0015] It should be understood that the above general description and the following detailed description are exemplary and explanatory only, and do not limit this application. Attached Figure Description

[0016] The accompanying drawings, which are incorporated in and form part of this specification, illustrate embodiments consistent with this application and, together with the description, serve to explain the principles of this application, and do not constitute an undue limitation of this application.

[0017] Figure 1 These are comparison images of PET images, PET / CT fusion images, and maximum density projection maps of the experimental and control groups provided in the embodiments of this application; Figure 2 These are hematoxylin-eosin staining control images of the experimental and control groups provided in the embodiments of this application; Figure 3 This is a comparison image of elastic fiber-Vangissen staining between the experimental and control groups provided in the embodiments of this application; Figure 4 These are immunohistochemical staining comparison images of the experimental group and the control group provided in the embodiments of this application; Figure 5 These are immunofluorescence staining control images of the experimental group and the control group provided in the embodiments of this application; Figure 6 These are PET and PET / CT fusion images of rapidly recurrent restenosis vessels provided in the embodiments of this application; Figure 7 These are PET and PET / CT fusion images of slowly progressive restenosis vessels provided in the embodiments of this application; Figure 8 These are PET and PET / CT fusion images of vessels without restenosis provided in the embodiments of this application; Detailed Implementation

[0018] To enable those skilled in the art to better understand the technical solutions of this application, the technical solutions in the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. It should be understood that the specific embodiments described herein are merely intended to explain this application and not to limit it. For those skilled in the art, this application can be implemented without some of these specific details. The following description of the embodiments is merely to provide a better understanding of this application by illustrating examples.

[0019] It should be noted that the terms "first," "second," etc., used in the specification, claims, and accompanying drawings of this application are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that such data can be interchanged where appropriate so that the embodiments of this application described herein can be implemented in orders other than those illustrated or described herein. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with this application. Rather, they are merely examples consistent with some aspects of this application as detailed in the appended claims.

[0020] Among related technologies, percutaneous coronary intervention (PCI) is commonly used for coronary artery disease. PCI involves placing a coronary stent within the narrowed coronary artery, effectively relieving myocardial ischemia and improving patient prognosis. After PCI, some patients may experience in-stent restenosis, one type of which is called rapid recurrent coronary in-stent restenosis (RECUR). RECUR is defined as three or more myocardial infarctions or target vessel revascularizations within one year of stent implantation via PCI due to coronary artery stenosis. The annual incidence of RECUR is approximately 1%–2%, accounting for 5%–10% of all PCI cases. The 3-year risk of cardiac death and myocardial infarction is significantly higher in RECUR patients than in those with conventional in-stent restenosis.

[0021] Coronary stent implantation causes arterial damage, triggering vascular smooth muscle cell proliferation and extracellular matrix deposition, which together lead to changes in the matrix composition of the arterial wall and intimal hyperplasia. This is the main mechanism of RECUR (Recurrent Embolism). Intravascular imaging techniques such as intravascular ultrasound and optical coherence tomography (OCT) can effectively identify newly formed atherosclerotic plaques and thrombi, but they are structural imaging techniques. Computed tomography coronary angiography can assess the density of pericoronary adipose tissue, but these techniques cannot directly visualize and assess the pathological processes driven by inflammation and proliferation, as well as the progression level of in-stent restenosis, in vivo.

[0022] Among related technologies, the average time to diagnosis of RECUR exceeds 12 months; conventional treatments have limited effectiveness for RECUR with high inflammatory burden and proliferative drive, requiring targeted anti-inflammatory therapy. Therefore, early and accurate assessment of the risk of developing RECUR is crucial. However, currently, there are no effective non-invasive imaging techniques for RECUR risk assessment.

[0023] To address the aforementioned issues, embodiments of this application provide an imaging agent for evaluating rapidly recurrent in-stent restenosis of the coronary arteries. The imaging agent targets fibroblast activating proteins and includes a radionuclide-labeled fibroblast activating protein inhibitor, which specifically binds to the fibroblast activating proteins.

[0024] Fibroblasts are a common cell type in connective tissue, responsible for synthesizing and maintaining the extracellular matrix. Under physiological conditions, fibroblasts are in a resting state with low functional activity. When tissues are injured, inflamed, or subjected to mechanical stress, fibroblasts are activated and transform into activated fibroblasts. Activated fibroblasts are star-shaped or bundled and secrete large amounts of pro-inflammatory factors such as IL-17A and TNF-α, as well as the chemokine CCL2.

[0025] Fibroblast activating protein (FAP) is a type II transmembrane serine protease belonging to the prolyl oligopeptidase family, with a molecular weight of approximately 97 kDa. FAP expression is extremely low in normal adult tissues; however, it is highly expressed on the surface of activated fibroblasts and is almost entirely absent on resting fibroblasts or other normal cells (endothelial cells, smooth muscle cells, macrophages). Therefore, FAP is one of the specific markers of fibroblast activating proteins.

[0026] Fibroblast activating protein inhibitor (FAPI) is a small molecule compound that specifically binds to the enzyme active site of FAP, thereby inhibiting FAP protease activity. When FAPI is labeled with a radionuclide, it becomes a radioactive tracer. The radionuclide-labeled FAPI specifically binds to fibroblast activating proteins. By observing the distribution characteristics of the radionuclide label, the distribution characteristics of fibroblast activating proteins and activated fibroblasts can be analyzed.

[0027] In patients with recurrent fibroblastic renal activator protein 1 (RECUR), the level of low-density lipoprotein receptor-associated protein 1 (LRP1) gene-encoded RNA in peripheral blood is significantly elevated, and its expression level is highly positively correlated with pro-inflammatory factors IL-17A and TNF-α. LRP1, as a key regulator of pro-inflammatory function in fibroblasts, can activate the c-Jun pathway, promote CCL2 secretion, and thus drive the fibroblast-M1 macrophage inflammatory cascade. Therefore, activated fibroblasts, which are closely related to the inflammatory mechanism of RECUR, can serve as targets for assessing RECUR risk. Imaging agents, including radionuclide-labeled fibroblast activation protein inhibitors, can be used to trace the distribution characteristics of activated fibroblasts, thereby assessing RECUR risk based on these distribution characteristics. Since radionuclide-labeled fibroblast activation protein inhibitors can be visualized using radionuclide imaging techniques, the inflammatory and fibrotic proliferative lesion characteristics of RECUR can be specifically visualized through imaging images, enabling timely identification of the occurrence of RECUR.

[0028] In the imaging agent provided in this application for evaluating rapidly recurrent coronary artery in-stent restenosis, by including a radionuclide-labeled fibroblast activator protein inhibitor in the imaging agent, the imaging agent tracer can specifically target and activate fibroblasts. The radionuclide-labeled fibroblast activator protein inhibitor can be visualized using radionuclide imaging technology, thereby specifically visualizing activated fibroblasts through the imaging images. This allows for the identification of inflammatory and fibrotic proliferative lesion characteristics of RECUR through activated fibroblasts, and the risk of RECUR can be assessed based on the distribution characteristics of activated fibroblasts.

[0029] In some embodiments, the developing agent includes a fibroblast activator protein inhibitor precursor and a radionuclide, wherein the fibroblast activator protein inhibitor precursor is labeled with the radionuclide.

[0030] The fibroblast activator protein inhibitor precursor is used to specifically target and bind to fibroblast activator proteins, enabling the fibroblast activator protein inhibitor to bind to FAP with high affinity and high specificity. Optionally, the active structure of the fibroblast activator protein inhibitor precursor is 5-iodoquinoline-4-amide.

[0031] Radionuclides are used for diagnostic imaging. Optionally, radionuclides include... 18 F, 68 Ga、 64 Cu、 99m Tc, 90 Y、 225 Ac、 125 I, 131 At least one of I.

[0032] In some embodiments, the fibroblast activator protein inhibitor precursor includes at least one of FAPI-04, FAPI-42, FAPI-34, FAPI-74, DP-FAPI, or iFAPI, and the fibroblast activator protein inhibitor precursor is coupled with a radionuclide.

[0033] In some embodiments, information on the uptake intensity of fibroblast activator protein inhibitors in the heart and coronary artery regions of subjects who have received imaging agents is positively correlated with the risk of rapid recurrent in-stent restenosis of the coronary arteries.

[0034] An imaging agent was administered to the subjects, and radionuclide imaging was used. Analysis of the images revealed the uptake intensity of the subjects' hearts and coronary arteries, which was correlated with the degree of inflammatory-proliferative activity. Weaker uptake intensity correlated with a lower risk of rapid recurrent in-stent restenosis, while stronger uptake intensity correlated with a higher risk.

[0035] Thirdly, the application of imaging agents, as described above, in evaluating rapidly recurrent in-stent restenosis of the coronary arteries is also provided.

[0036] Since the developer provided in any of the above embodiments is used, it has the same technical effect, which will not be described in detail here.

[0037] Fourthly, a method for evaluating rapidly recurrent in-stent restenosis of the coronary arteries is provided, comprising the following steps: S1, administer an effective dose of the imaging agent as described above to the subject; S2, using radionuclide imaging technology to acquire images of the subject's heart and coronary artery region; S3, analyze the distribution characteristics of radionuclides in the image, and assess the distribution characteristics and activation level of fibroblasts based on the distribution characteristics; S4 is used to assess the risk of rapidly recurrent in-stent restenosis of the coronary arteries based on the distribution characteristics and activation level of fibroblast activating proteins.

[0038] Optionally, in S2, CT images of the subject's heart and coronary artery region can be obtained using CT imaging technology, and PET images of the subject's heart and coronary artery region can be obtained using PET imaging technology. The CT images and PET images are then fused to obtain a fused image. In S3, the distribution characteristics of radionuclides in the fused image are analyzed, and the distribution characteristics and activation level of fibroblasts are assessed based on these characteristics. By fusing CT and PET images to obtain a fused image, the location of the metal implant (which can be all or part of a coronary artery stent) can be identified using the CT image; the location of activated fibroblasts can be determined using the PET image. The metal implant and surrounding activated fibroblasts in the fused image can be precisely registered, thereby determining the source of restenosis risk.

[0039] In some embodiments, S2 further includes: CT images of the heart and coronary artery regions of the subjects were obtained using CT imaging technology, and the CT images were processed based on attenuation correction and scattering correction. PET images of the heart and coronary artery regions of the subject were obtained using PET imaging technology, and the PET images were processed using the ultraHD-PET algorithm. The processed CT and PET images are fused to obtain a fused image.

[0040] In one embodiment, the distribution features include ingestion spatial distribution and ingestion intensity information.

[0041] Spatial uptake distribution characterizes the three-dimensional spatial distribution of the imaging agent in the cardiac and coronary artery regions. Uptake intensity information characterizes the amount of radionuclide per unit tissue volume, reflecting the expression of FAP.

[0042] In some embodiments, the uptake intensity information includes the maximum standard uptake value (SUVmax) and the maximum lesion-to-background ratio (TBRmax); S4 includes: When SUVmax is less than or equal to the first preset threshold and TBRmax is less than or equal to the second preset threshold, the risk of rapid recurrent in-stent restenosis of the coronary arteries is generated as relatively low. When SUVmax is greater than the first preset threshold and TBRmax is greater than the second preset threshold, the subject is considered to have a relatively high risk of rapid recurrent in-stent restenosis. The first preset threshold is 1.30~3.86; the second preset threshold is 1.55~4.27, and the first preset threshold is less than the second preset threshold.

[0043] Preferably, the first preset threshold is 2.47; the second preset threshold is 2.75.

[0044] SUVmax is the highest radioactivity concentration measured at a single pixel in the coronary artery stent region. TBRmax is the SUVmax of the coronary artery stent region divided by the SUVmax of normal myocardium or blood pool to eliminate individual differences.

[0045] Since the biomarkers provided in any of the above embodiments are used, they have the same technical effects, which will not be repeated here.

[0046] To verify the effects achievable by the above embodiments, the following embodiments and comparative examples are provided for illustration: Example 1: Constructing a rapid recurrence coronary artery in-stent restenosis model.

[0047] All mice were provided by the Shanghai Southern Model Organism Research Center (product number NM-KO-210110). All mice were housed in a specific pathogen-free environment with a 12-hour / 12-hour light / dark cycle and were given free access to standard rodent feed. Twelve-week-old male mice were used due to their larger size, which facilitated guidewire angioplasty and minimized surgical stress.

[0048] The procedure for guidewire-induced femoral artery injury under anesthesia is as follows: The thigh skin is incised to expose the rectus femoris and vastus medialis muscles. The vessels and nerves surrounding the femoral artery are meticulously dissected and exposed. Blood flow is temporarily blocked by wrapping the vessel with 4-0 silk suture. Another 4-0 silk suture is placed below the branch vessel. A transverse arterial incision is made at the branch. A 0.35mm flexible angioplasty guidewire is inserted >5mm into the femoral artery towards the iliac artery, and vascular dilation and endothelial stripping are performed for 3 minutes. The branch vessel is ligated with 7-0 sutures, and the ligation sutures are released to restore blood flow. The incision is sutured with 4-0 silk sutures.

[0049] Example 2: Application of imaging agent to a rapid recurrence coronary artery in-stent restenosis model.

[0050] Twenty-eight days after guidewire injury in a rapid recurrent coronary artery in-stent restenosis model, four mice with rapid recurrent coronary artery in-stent restenosis were used as the experimental group, and four mice without guidewire-induced femoral artery injury were used as the control group. Mice were fasted for 4 hours but had free access to water. Anesthesia was induced and maintained with 2% isoflurane using inhaled oxygen. Imaging agents were injected via the tail vein. 18F-FAPI was approximately 3.7-5 MBq in volume, 100 uL. Sixty minutes post-injection, a 10-minute static PET scan was performed using a small animal PET / CT scanner (MIRA Micro PET-CT, MIPWC-1041, Ping Sheng Technology). Following the PET scan, a low-dose CT scan was performed with an exposure time of 300 ms and a voltage of 50 kVp for anatomical localization and attenuation correction. Image reconstruction was performed using the ordered subset maximum expectation algorithm. Image reconstruction and analysis were performed using Hermes software. On the fused PET / CT images, regions of interest (ROIs) were delineated along the femoral artery, identifying the femoral artery injury and the contralateral normal vessel. The radioactive uptake values ​​of each ROI were calculated, with the standard uptake value (SUVmax) as the uptake index.

[0051] like Figure 1 As shown, the imaging agent was injected. 18 Sixty minutes after F-FAPI administration, no abnormally high uptake was observed in the bilateral femoral artery region of the control group, while focal areas of increased uptake were visible in the bilateral femoral artery region of the experimental group, as indicated by the arrows in the figure. Therefore, the imaging agent... 18 In the experimental group of mice, F-FAPI showed significant focal radioactive concentration in the femoral artery, which was significantly higher than that in the normal femoral artery of the control group. The SUVmax values ​​were 1.62±0.47 and 0.28±0.8, respectively, with a statistical test P<0.0001.

[0052] Example 3 Referring to Example 2, imaging agents were injected via the tail vein into multiple mouse models of rapid recurrent coronary artery in-stent restenosis. 68 Ga-FAPI-04 18 F-FAPI-04 18 F-FAPI-42, 18 F-FAPI-74, 99m Tc-FAPI-04 99m Tc-iFAP, 64 Cu-FAPI-42 90 Y-FAPI-74 225 Ac-DP-FAPI, 125 I-iFAPI, 131 I-FAPI-04. Sixty minutes after injection of the imaging agent, significant focal radioactive concentration was observed in the femoral artery lesions of mice, which was significantly higher than that in the normal femoral artery of the control group.

[0053] Example 4 validates the reliability of imaging agents in assessing rapid recurrent in-stent restenosis of the coronary arteries.

[0054] Twenty-eight days after guidewire injury in a rapid recurrent coronary artery in-stent restenosis model, mice were fixed and euthanized after 5 mL formalin perfusion to the left ventricle. Femoral artery samples were obtained and embedded in paraffin for morphometric and histological analysis. Mice that did not undergo guidewire-induced femoral artery injury served as the control group. Hematoxylin-eosin (HE) staining, elastic-Van Gieson (EVG) staining, immunohistochemical staining, and immunofluorescence staining were performed. For immunohistochemical staining, the primary antibody was anti-fibroblast activator protein α antibody (abcam, catalog number ab53066, 1:100); for immunofluorescence staining, the primary antibody was a macrophage marker CD68 antibody and a rabbit monoclonal antibody (Cell Signaling Technology, catalog number 76437, 1:200).

[0055] like Figure 2 and Figure 3 As shown, compared with the control group, the experimental group showed significant proliferation of the femoral artery intima and adventitia obtained on day 28 after injury, indicating successful establishment of the mouse restenosis model.

[0056] like Figure 4 As shown, compared with the control group, the expression level of fibroblast activation protein in the neointima and adventitia of the femoral artery obtained 28 days after guidewire injury was significantly higher in the experimental group than in the control group.

[0057] like Figure 5 As shown, the number of femoral artery macrophages after guidewire injury was significantly higher in the experimental group compared to the control group.

[0058] In summary, this indicates that the experimental group suffered from rapidly recurrent in-stent restenosis of the coronary arteries, and the imaging agent... 18 F-FAPI showed significant focal radioactive concentration in the femoral artery of mice in the experimental group.

[0059] Example 5 validates the use of imaging agents to assess the recurrence risk of rapid recurrent in-stent restenosis in coronary arteries.

[0060] Subjects were administered an effective dose of the imaging agent 18F-FAPI, and PET / CT fusion images of the heart and coronary artery regions were acquired using radionuclide imaging. The imaging agent uptake distribution characteristics were analyzed based on the PET / CT fusion images. PET images were reconstructed using the ultraHD-PET algorithm (TrueX TOF; 4 iterations, 5 subsets), and CT images were processed based on CT attenuation and scattering correction (120 kV, automatic mAs). An additional metal artifact correction algorithm was employed to minimize interference from metal stents.

[0061] The processed images were analyzed to obtain the distribution characteristics of radionuclides, and SUVmax and TBRmax were generated based on these characteristics. A first preset threshold of 2.47 and a second preset threshold of 2.75 were set to assess the risk of rapid recurrent in-stent restenosis in the subject.

[0062] like Figure 6 As shown, this is a vessel with high uptake of imaging agent in the coronary stent course area, where SUVmax is 4.94 and TBRmax is 5.09, indicating a relatively high risk for rapidly recurrent in-stent restenosis. In-stent restenosis occurred rapidly 4 months after treatment.

[0063] like Figure 7 As shown, this is a vessel with mild uptake of imaging agent in the coronary artery stent course area, where SUVmax is 1.85 and TBRmax is 2.06, indicating a relatively low risk for rapidly recurrent in-stent restenosis. Restenosis occurred 3 years after stent placement.

[0064] like Figure 8 As shown, in the coronary artery stent course area, no significant uptake of imaging agent was observed in the vessels, indicating stent patency. The SUVmax was 1.30 and TBRmax was 1.37, classifying the risk of rapid recurrent in-stent restenosis as relatively low. No restenosis occurred 2 years post-placement. This demonstrates a positive correlation between imaging agent uptake intensity and the risk of rapid recurrent in-stent restenosis within the coronary artery stent implantation area.

[0065] It should also be noted that the exemplary embodiments mentioned in this application describe methods, complexes, or kits based on a series of steps. However, this application is not limited to the order of the above steps; that is, the steps can be performed in the order mentioned in the embodiments, or in a different order, or several steps can be performed simultaneously.

[0066] The above are merely specific embodiments of this application. Those skilled in the art will clearly understand that, for the sake of convenience and brevity, the methods, complexes, and kits described above can be referred to the corresponding descriptions in the foregoing connective body embodiments, and will not be repeated here. It should be understood that the scope of protection of this application is not limited thereto. Any person skilled in the art can easily conceive of various equivalent modifications or substitutions within the scope of the technology disclosed in this application, and these modifications or substitutions should all be covered within the scope of protection of this application.

Claims

1. An imaging agent for evaluating rapidly recurrent in-stent restenosis of the coronary arteries, characterized in that, The imaging agent targets fibroblast activation proteins, and the imaging agent includes a radionuclide-labeled fibroblast activation protein inhibitor, which is used to specifically bind to fibroblast activation proteins.

2. The developer according to claim 1, characterized in that, The imaging agent comprises a fibroblast activator protein inhibitor precursor and a radionuclide, wherein the fibroblast activator protein inhibitor precursor labels the radionuclide.

3. The developer according to claim 2, characterized in that, The active structure of the fibroblast activator protein inhibitor precursor is 5-iodoquinoline-4-amide.

4. The developer according to claim 2, characterized in that, The radionuclides include 18 F, 68 Ga、 64 Cu、 99m Tc, 90 Y、 225 Ac、 125 I, 131 At least one of I.

5. The developer according to claim 2, characterized in that, The fibroblast activator protein inhibitor precursor includes at least one of FAPI-04, FAPI-42, FAPI-34, FAPI-74, DP-FAPI, or iFAPI, and the fibroblast activator protein inhibitor precursor is coupled with the radionuclide.

6. The developer according to claim 1, characterized in that, The uptake intensity of the fibroblast activator protein inhibitor in the heart and coronary artery regions of subjects who received the imaging agent was positively correlated with the risk of the subjects developing the rapid recurrent in-stent restenosis of the coronary arteries.

7. The use of the imaging agent as described in claims 1 to 6 in evaluating rapid recurrent in-stent restenosis of the coronary arteries.

8. A method for evaluating rapidly recurrent in-stent restenosis of the coronary arteries, characterized in that, Includes the following steps: Administering an effective dose of the imaging agent as described in any one of claims 1 to 6 to the subject; Images of the subject's heart and coronary artery regions were acquired using radionuclide imaging technology; The distribution characteristics of radionuclides in the images were analyzed, and the distribution characteristics and activation degree of fibroblast activation proteins were evaluated based on the distribution characteristics. The risk of rapid recurrent in-stent restenosis in coronary arteries is assessed based on the distribution characteristics and activation level of the fibroblast activation proteins.

9. The method for evaluating rapidly recurrent in-stent restenosis of the coronary arteries according to claim 8, characterized in that, The distribution characteristics include ingestion spatial distribution and ingestion intensity information.

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