Application of Ga-labeled peritoneal fibrosis marker PET tracer in peritoneal dialysis related peritoneal fibrosis diagnostic product

Abstract

The invention discloses application of a Ga-labeled peritoneal fibrosis marker PET tracer agent in peritoneal dialysis related peritoneal fibrosis diagnosis products, and belongs to the technical field of peritoneal function detection. According to the method, fibroblast activating protein, a discoid structural domain receptor 2, integrin linked kinase and the like are selected as peritoneal fibrosis markers, and gallium 68 is used for marking, so that the PET tracer is prepared. The tracer agent can be specifically combined to peritoneal fibrosis tissue, and PET imaging with high sensitivity and high specificity is achieved. Meanwhile, the invention also provides a corresponding PET diagnostic kit which integrates a tracer agent, a purified buffer solution, a stabilizer and image analysis software, so that the operation process is simplified, and the detection efficiency is improved. By means of the method, noninvasive and accurate detection of peritoneal fibrosis can be achieved, a scientific basis is provided for selection and adjustment of peritoneal dialysis schemes, the progress condition of peritoneal fibrosis can be continuously monitored, a treatment scheme can be adjusted in time, the dialysis time of peritoneal dialysis patients is expected to be prolonged, and the life quality is improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of peritoneal function detection, and in particular relates to an application of a Ga-labeled peritoneal fibrosis marker PET tracer in a peritoneal fibrosis diagnosis product associated with peritoneal dialysis. Background Art

[0002] Peritoneal dialysis (PD) is a high-quality, low-cost, and convenient renal replacement therapy. It is one of the important home dialysis treatments for patients with end-stage renal failure (ESRD). It has the advantages of protecting residual renal function, simple operation, low cost, and high social return rate. PD can not only be used for long-term home dialysis treatment of patients with chronic renal failure, but also for emergency life support treatment of multiple organ failure after cardiac surgery, battlefield injuries, etc. The implementation of peritoneal dialysis mainly relies on the human peritoneum as a key filtration membrane, but under the stimulation of factors such as long-term high-concentration dialysate, the expression of molecules such as transcription growth factor β (TGF-β) and integrin-linked kinase (ILK) in the peritoneum increases, leading to peritoneal mesothelial cell transdifferentiation (MMT), which in turn activates fibroblasts, promotes capillary proliferation and collagen fiber deposition, and may eventually cause peritoneal fibrosis, leading to peritoneal dialysis failure. At present, the assessment of peritoneal function mainly relies on dialysis equilibrium test and calculation of Kt / V value. These methods require 1-2 days of abdominal stay, specimen testing and complex calculation. The process is complicated, invasive and time-consuming, and the patient compliance is poor. In addition, these methods can only indirectly assess the degree of peritoneal fibrosis through the clearance rate of glucose and creatinine through the peritoneum, and the results are not intuitive and accurate. The early symptoms of peritoneal fibrosis are often not obvious, and traditional imaging methods are difficult to accurately diagnose. Therefore, a simple and easy-to-use method for early diagnosis and progression monitoring of peritoneal fibrosis is urgently needed in the clinic to achieve the sustainability of PD treatment and improve the quality of life of patients.

[0003] Positron emission computed tomography (PET) is a non-invasive nuclear medicine detection technology with directional positioning and functional development, which is widely used in the detection of fibrosis in other organs and tissues. PET uses compounds labeled with positron nuclides as tracers to trace the corresponding physiological and biochemical processes or special structures in the body, achieving non-invasive and accurate development of specific parts; and by collecting the intensity of radionuclides, quantitative analysis of the marked parts can be achieved. In the field of fibrosis detection, studies have explored the application of PET tracers labeled with fibroblast activation protein (FAP) (such as 68Ga-FAPI) in the detection of liver fibrosis. It has good application prospects in the detection of liver fibrosis and has high accuracy in assisting the grading of liver cirrhosis. However, there has been no relevant research on its application in the early diagnosis of peritoneal fibrosis related to peritoneal dialysis and the evaluation and prediction of peritoneal ultrafiltration function. Therefore, the development of a Ga-labeled peritoneal fibrosis marker PET tracer for the early diagnosis and progression monitoring of peritoneal fibrosis related to peritoneal dialysis has important clinical significance and application value. Discoidin domain receptor 2 (DDR2) is a tyrosine kinase receptor that is primarily involved in signal transduction from fibrillar collagen and plays a central role in the fibrosis process. Clinical evidence shows that the expression of DDR2 in the lung tissue of patients with idiopathic pulmonary fibrosis is 100 times higher than that in the lung tissue of healthy people. Integrin-linked kinase ILK is an important signaling protein that is ubiquitously expressed throughout the body. It binds to intracellular integrins and helps promote signal transduction associated with cell adhesion, apoptosis, proliferation, migration, and a large number of other common cell functions, but DDR2 and ILK are more studied as potential targets for tumor treatment rather than directly used for non-invasive detection of fibrosis. The number of patients with peritoneal dialysis-related peritoneal fibrosis leading to peritoneal dialysis failure is increasing year by year. However, there is no accurate and non-invasive detection method to evaluate peritoneal dialysis-related peritoneal fibrosis, which poses a great challenge to the early clinical evaluation of the patient's peritoneal transport status and is not conducive to early intervention of patients, leading to peritoneal dialysis failure. Summary of the invention

[0004] In view of the problems that the existing peritoneal fibrosis diagnostic methods are complicated, invasive, time-consuming and the results are not intuitive, there is an urgent need for an accurate and non-invasive detection method to evaluate the technical status of peritoneal fibrosis associated with peritoneal dialysis. The present invention aims to provide a Ga-labeled peritoneal fibrosis marker PET tracer for use in peritoneal dialysis-related peritoneal fibrosis diagnostic products, providing a feasible new idea and method for the non-invasive diagnosis of peritoneal fibrosis.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions: The present invention provides an application of a Ga-labeled peritoneal fibrosis marker PET tracer in the preparation of a peritoneal dialysis-related peritoneal fibrosis early diagnosis and progression monitoring product.

[0006] The Ga-labeled peritoneal fibrosis marker PET tracer is formed by coupling Ga with a ligand or antibody of the peritoneal fibrosis marker.

[0007] The peritoneal fibrosis marker is selected from at least one of fibroblast activation protein, discoidin domain receptor 2 and integrin linked kinase.

[0008] The product for peritoneal fibrosis diagnosis is a PET imaging agent, a radiopharmaceutical preparation or a kit for in vitro diagnosis.

[0009] The present invention provides a Ga-labeled peritoneal fibrosis marker PET tracer, wherein the PET tracer is formed by coupling Ga with a ligand or antibody of at least one peritoneal fibrosis marker selected from fibroblast activation protein, discoidin domain receptor 2 and integrin-linked kinase, and is used for tracking and imaging the location and extent of peritoneal fibrosis associated with peritoneal dialysis.

[0010] The preparation method of the PET tracer of the gallium-68 labeled peritoneal fibrosis marker comprises: dissolving the peritoneal fibrosis marker in a sodium bicarbonate solution, adding a bifunctional chelating agent DOTA, mixing and incubating; removing the unbound chelating agent to obtain a successfully coupled DOTA-peritoneal fibrosis marker; dissolving the DOTA-peritoneal fibrosis marker in a sodium acetate solution, then slowly adding a 68GaCl3 eluent to the protein solution in proportion, adjusting the pH value to 3.5-4.0, and reacting at 37°C to obtain a PET tracer of the gallium-68 labeled peritoneal fibrosis marker.

[0011] The present invention provides a PET diagnostic kit for detecting peritoneal dialysis-related peritoneal fibrosis, wherein the PET diagnostic kit comprises the PET tracer of the Ga-labeled peritoneal fibrosis marker.

[0012] The PET diagnostic kit also includes reagents and auxiliary tools for preparing PET tracers.

[0013] The PET diagnostic kit also includes software tools for PET image analysis.

[0014] The present invention provides a non-invasive detection method for non-disease diagnosis and treatment of peritoneal dialysis-related peritoneal fibrosis based on PET, based on the above-mentioned Ga-labeled peritoneal fibrosis marker PET tracer, PET imaging, and evaluating the degree of fibrosis according to the SUV value of the imaging result.

[0015] Compared with the prior art, the present invention has the following beneficial effects: The application of the Ga-labeled peritoneal fibrosis marker PET tracer provided by the present invention in the preparation of peritoneal dialysis-related peritoneal fibrosis early diagnosis and progression monitoring products has significant technical effects and social value. It will bring new hope and possibilities for the diagnosis and treatment of peritoneal dialysis patients. Traditional peritoneal fibrosis diagnosis methods often rely on invasive examinations, such as peritoneal biopsy. The PET tracer of the present invention realizes non-invasive diagnosis of peritoneal fibrosis through PET imaging technology, thus avoiding the pain and risks of examination for patients; due to the high sensitivity and specificity of the PET tracer, lesions can be detected in the early stage of peritoneal fibrosis, thus providing the possibility for early intervention and treatment; through PET imaging technology, the progress of peritoneal fibrosis can be monitored in real time, and the severity and development trend of peritoneal fibrosis can be evaluated according to the changes in the distribution of the tracer in the PET image; based on the real-time monitoring of peritoneal fibrosis by PET tracer, personalized treatment plans can be formulated for patients; early detection and intervention of peritoneal fibrosis can help reduce complications caused by peritoneal fibrosis, and through early diagnosis and real-time monitoring of peritoneal fibrosis, unnecessary medical intervention and treatment can be avoided, thereby reducing medical costs; non-invasive diagnosis and real-time monitoring reduce the pain and risks of examination for patients and improve patient compliance.

[0016] The Ga-labeled peritoneal fibrosis marker PET tracer provided by the present invention can specifically bind to activated fibroblasts in peritoneal fibrosis tissue. This specific binding makes the tracer highly aggregated in the peritoneal fibrosis area, thereby forming a clear lesion display in the PET image; due to the high sensitivity and specificity of the PET tracer, it can detect lesions in the early stage of peritoneal fibrosis. This is of great significance for early diagnosis and timely intervention, which helps to delay disease progression and improve patient prognosis; through PET images, the peritoneal fibrosis area can be quantitatively analyzed, which helps to more accurately judge the severity and development trend of peritoneal fibrosis; the PET tracer ensures the high affinity, long retention time and low toxicity of the tracer in the body, thereby achieving high-quality PET images, not only having good biocompatibility and stability, but also being able to efficiently and specifically bind to peritoneal fibrosis markers, significantly improving the sensitivity and specificity of PET imaging, and providing clinicians and researchers with intuitive and clear lesion images.

[0017] The diagnostic kit of the present invention integrates PET tracers, purification buffers, stabilizers and image analysis software, which greatly simplifies the operation process and improves the detection efficiency. It not only supports the smooth progress of PET imaging, but also provides image analysis software to help doctors quickly and accurately interpret PET images, further improving the accuracy and reliability of diagnosis.

[0018] The present invention provides a non-invasive detection method for non-disease diagnosis and treatment of peritoneal dialysis-related peritoneal fibrosis based on PET, which realizes non-invasive and accurate detection of peritoneal fibrosis and avoids the pain and risks caused by traditional invasive detection methods; by quantitatively analyzing the severity of peritoneal fibrosis, a scientific basis is provided for the selection and adjustment of peritoneal dialysis plans, realizing individualized and accurate treatment plans; it can continuously monitor the progress of peritoneal fibrosis, adjust the treatment plan in time, and improve the treatment effect and the quality of life of patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is the technical roadmap of the non-invasive detection method of peritoneal dialysis-related peritoneal fibrosis based on PET of the present invention.

[0020] Figure 2 is a peritoneal fibrosis marker of the present invention; Figure 3 This is a flow chart of the animal experiment of the present invention; Figure 4 This is a flow chart of the clinical trial of the present invention; Figure 5 This is a flow chart of the peritoneal balance experiment of the present invention; Figure 6 The figures are the results of the animal pre-experiment of the present invention; A is a peritoneal dialysis-related peritoneal fibrosis mouse model (Masson staining); B is the expression of FAP, DDR2, and ILK in the fibrotic peritoneum of the model animal; C is the development of FAP labeled with 68Ga-FAPI as a tracer in the animal model; Figure 7 These are the results of the clinical pilot experiment of the present invention, wherein A is the expression of FAP, DDR2, and ILK in the fibrotic peritoneum of peritoneal dialysis patients (IHC staining); B is the expression of FAP and Merge (immunofluorescence) and statistical analysis results; C is the PET image after 68Ga-FAPI development in the control group. DETAILED DESCRIPTION

[0021] In order to enable those skilled in the art to better understand the scheme of the present invention, the technical scheme in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the present invention.

[0022] The use of patient samples involved in this invention has been approved by the Medical Ethics Committee of the First Affiliated Hospital of Air Force Medical University (ID: KY20232347-F-1), and all patients have signed informed consent.

[0023] The present invention is further described in detail below in conjunction with the accompanying drawings: Figure 1 The technical roadmap of the present invention is a non-invasive detection method for peritoneal dialysis-related peritoneal fibrosis based on PET, and the specific steps are as follows: 1. Screening and validation of biomarker molecules 1. Screening molecules 1.1 Literature screening Combining the current research progress of PET molecular imaging technology and the new discovery of peritoneal fibrosis, we analyzed the literature database such as Pubmed and combined with the mechanism of peritoneal fibrosis to identify three marker molecules of PD-related peritoneal fibrosis, namely FAP, DDR2, and ILK. Figure 2 It is a marker molecule screened by the present invention.

[0024] 1.2 Bioinformatics analysis of differentially expressed molecules The gene expression comprehensive database GEO was used to collect gene sequencing information of human peritoneal tissue, and the gene expression information was processed using a machine learning method using a public R data package. The limma model was established to preliminarily screen genes differentially expressed in fibrotic peritoneum. On this basis, the genes screened out were used for LASSO modeling and random forest modeling, and the results were comprehensively processed to obtain the intersection. The data set was internally verified to verify the effectiveness of the screened genes, and finally no more than 6 differentially expressed molecules were screened out.

[0025] 2. Verification of Molecular Expression in Peritoneal Tissue 2.1 Verification of the expression of FAP, DDR2, and ILK in animal peritoneal tissue ① Grouping and modeling: The control group and the experimental group were intraperitoneally injected with PBS or 4.25% peritoneal dialysis fluid at 0.1 mL / g, respectively, to establish a peritoneal dialysis-related peritoneal fibrosis mouse model with 3 mice in each group on days 0, 7, 14, and 28.

[0026] ② Obtain peritoneal tissue from the control group and experimental group model mice.

[0027] ③The expression of peritoneal fibrosis marker molecules screened by immunohistochemistry was detected, and the relative quantitative results between the experimental group and the control group were compared.

[0028] 2.2 Verification of FAP, DDR2, and ILK expression in patient peritoneal tissue ① Grouping: The paraffin sections of peritoneal tissue obtained from patients through peritoneal dialysis catheterization and extubation were divided into low, medium and high groups according to the patients' peritoneal dialysis time, and 3 specimens were randomly included in each group.

[0029] The group with a penetration age of less than 12 months was the low penetration age group; the group with a penetration age of 12-24 months was the medium penetration age group; and the group with a penetration age of more than 24 months was the high penetration age group.

[0030] ②The expression of peritoneal fibrosis marker molecules screened by immunohistochemistry was detected, and the relative quantitative results between the experimental group and the control group were compared.

[0031] 2.3 Preliminary verification of specific biomarkers screened by machine learning models The above-mentioned model animal specimens and patient specimens were used for immunohistochemical staining of specific biomarkers, the expression of which was compared between the experimental group and the control group, and a relative quantitative analysis was performed to preliminarily explore the feasibility of using bioinformatics analysis to screen specific biomarkers for peritoneal fibrosis.

[0032] 2. Animal experiments See attached Figure 3-5 As shown, ① Grouping and modeling: The control group and the experimental group were intraperitoneally injected with PBS or 4.25% peritoneal dialysis fluid at 0.1 mL / g, respectively, to establish a peritoneal dialysis-related peritoneal fibrosis mouse model with 9 mice in each group on days 0, 7, 14, and 28.

[0033] ①Injection 68 Ga positron emission tomography marker molecules 68 Ga-FAPI, 68 Ga-DDR2, 68 Ga-ILK, for PET imaging and collection of SUV values; The peritoneal fibrosis marker was dissolved in sodium bicarbonate solution, and the bifunctional chelator DOTA was added, mixed and incubated; after removing the unbound chelator, the successfully coupled DOTA-peritoneal fibrosis marker was obtained; the DOTA-peritoneal fibrosis marker was dissolved in sodium acetate solution, and then 68GaCl3 eluent was slowly added to the protein solution in proportion, the pH value was adjusted to 3.5~4.0, and the reaction was carried out at 37°C to obtain a PET tracer for gallium-68 labeled peritoneal fibrosis marker.

[0034] ②Evaluation of mouse peritoneal transport function 4.25% peritoneal dialysis fluid was injected intraperitoneally. 4 hours later, the concentrations of creatinine in mouse serum and peritoneal dialysis fluid were measured by ELISA as D(Cr) and P(Cr), respectively. 4 hours later, the concentration of glucose in peritoneal dialysis fluid was measured by ELISA as D(glu). D / P(Cr) and D(glu) / D0 were calculated to evaluate the peritoneal transport function of mice.

[0035] ③ Obtain mouse retroperitoneal treatment IHC, Masson staining and other methods were used to evaluate peritoneal fibrosis from a histological perspective; qPCR and WB were used to evaluate the expression of marker molecules FAP, DDR2, ILK and fibrosis molecules fibronectin, type I collagen and other transcriptional and translational levels. Relative quantitative statistics were performed on the histological results and molecular biological results. For details, see the attached Figure 6 shown.

[0036] By the attached Figure 6 The data showed that the peritoneal dialysis-related peritoneal fibrosis mouse model was successfully created (Masson staining). Masson staining showed that the 7-day, 14-day, and 28-day groups had obvious staining of the fibrosis area compared with the control group, with a disordered distribution, which directly proved that the monodermal mesenchymal cells successfully completed the mesenchymal transformation process, that is, these cells have been transformed into fibrosis-producing cell types. Compared with the control group, the significance and distribution characteristics of the fibrosis area both indicate that the model was successfully constructed, and the progression of fibrosis can be observed at different time points; Expression of FAP, DDR2, and ILK in the fibrotic peritoneum of model animals. Tissue sections (immunohistochemistry) of the control group and the 28-day group were found to be positively expressed in the fibrotic peritoneum of model animals by PET tracing, and this finding was further verified by PET tracing technology. The positive expression of these markers indicates that the fibrosis process has been effectively induced and maintained in the model animals. The expression of two fibrosis indicators, COL-1 (observed by Masson staining) and FN (observed by immunohistochemistry), increased in the peritoneum, and combined with the results of HE staining, once again confirmed the successful construction of the mouse model in terms of fibrosis. These results together support the validity and reliability of the model.

[0037] 68 Ga-FAPI was used as a tracer to mark the development of FAP in the fibrotic peritoneum of model animals. 68 As a specific tracer of FAP, Ga-FAPI was successfully visualized in the fibrotic peritoneum of the model animal, indicating that the tracer can specifically bind to FAP and reflect the expression changes of FAP during the fibrosis process; and as the number of modeling days increases, the SUVmax value also gradually increases, indicating that 68The expression of Ga-FAPI in fibrotic peritoneum gradually increased, which is consistent with the up-regulated expression of FAP during fibrosis. Through digital processing and statistical analysis of HC, Masson staining, qPCR and WB results, it was found that there was a statistical difference between the 7-day group and the control group, but there was no significant difference with other groups (such as the 14-day and 28-day groups). This result may indicate that the fibrosis process has begun to be significant at 7 days, but has not yet reached the fully mature stage at 14 days and 28 days. The results of the peritoneal balance test also support this, further confirming the effectiveness of the model in simulating peritoneal fibrosis.

[0038] By constructing a peritoneal dialysis-related peritoneal fibrosis mouse model and using a variety of technical methods such as Masson staining, immunohistochemistry, and PET tracing, the effectiveness and reliability of the model were successfully verified. 68 The application of Ga-FAPI as a tracer further revealed the expression changes of FAP during the fibrosis process, providing new ideas and methods for the non-invasive detection and monitoring of peritoneal fibrosis.

[0039] ④Statistical analysis: Use variance analysis to compare whether the results of the experimental group and the control group are different; and perform Pearson correlation analysis on the SUV value of PET and the results of traditional peritoneal equilibrium experiment, histology and molecular biology relative quantitative results; establish single-molecule and multi-molecule receiver operating characteristic (ROC) curves to compare the sensitivity and accuracy of single-molecule and multi-molecule PET tracers.

[0040] 3. Clinical trials verify 68 To investigate the accuracy and reliability of Ga-labeled FAP, DDR2, and ILK PET tracers for noninvasive detection of peritoneal fibrosis in humans and to evaluate their value as clinical diagnostic tools.

[0041] 1. Inclusion and setting of groups: 1.1 Inclusion criteria: Written informed consent was obtained from patients; aged 18-80 years; patients were newly diagnosed and required or were undergoing PD; patients underwent PET tracer development based on the balance test; the control group was people who did not undergo peritoneal dialysis.

[0042] 1.2 Exclusion criteria: patients with cachexia such as abdominal tumors; minors, pregnant women, and lactating women; patients with peritonitis; patients who need abdominal surgery during PD; and patients with a history of allergy to contrast agents or other drugs.

[0043] 1.3 Termination criteria: worsening of condition, serious adverse events, poor compliance 1.4 Grouping: The patients in the three groups were divided into three groups: the low age group (less than 12 months); the medium age group (12-24 months); and the high age group (more than 24 months). Each group included 9 patients. The patients in the low, medium, and high groups were randomly divided into 68 Ga-FAPI, 68 Ga-DDR2, 68 There were three subgroups of Ga-ILK and three in the control group.

[0044] 2. Perform peritoneal balance test to measure the patient's peritoneal function 2.1 According to the attached Figure 5 The process shown is used to perform peritoneal equilibrium test, and the dialysate creatinine Cr, urea nitrogen UN, and glucose Glu concentration results at 0h, 2h, and 4h, and the blood creatinine Cr, urea nitrogen UN, and glucose Glu concentration results at 2h; 2.2 Calculate the following results: D / Pcr=0h, 2h, 4h dialysate corrected creatinine value / blood creatinine, D / D0=2h, 4h dialysate glucose content / 0h dialysate glucose content.

[0045] Corrected creatinine = creatinine (mg / dL) - glucose x correction factor Creatinine correction factor = 2.5% fresh peritoneal dialysis fluid creatinine / glucose 2.3 Evaluate the patient's peritoneal function according to the criteria in Table 1 Table 1: Table for assessing peritoneal function

[0046] 3. PET test The day after the peritoneal equilibration test, the subgroups 68 Ga-FAPI, 68 Ga-DDR2, 68 Ga-ILK PET imaging, statistical SUV value; compare the differences between subgroups, as well as the differences in SUV values ​​between low, medium and high age groups. For specific experimental results, see the attached Figure 7 shown.

[0047] As a key indicator for measuring the uptake of radioactive tracers by tissues, SUV value can reflect the expression level of target molecules (such as FAP, DDR2, ILK) in fibrotic peritoneum. Figure 7The data show that FAP, DDR2, and ILK are expressed in the fibrotic peritoneum of peritoneal dialysis patients (IHC staining), showing differences in SUV values ​​between different subgroups (such as short dialysis age group, long dialysis age group, and control group), which helps us understand the dynamic changes of these molecules in the process of peritoneal fibrosis; by comparing the SUV values ​​of different subgroups, the SUV values ​​of patients in the short dialysis age group and the long dialysis age group were significantly higher than those in the control group, which further confirmed the upregulated expression of FAP, DDR2, and ILK in the process of peritoneal fibrosis; in addition, the difference in SUV values ​​between the short dialysis age group and the long dialysis age group may also reflect the different degrees of fibrosis, providing a quantitative basis for evaluating the progression of the disease. The immunohistochemistry results showed that the peritoneum of patients in the short dialysis age group and the long dialysis age group was significantly thicker than that in the control group, which is a direct manifestation of peritoneal fibrosis. Peritoneal thickening not only affects the efficiency of peritoneal dialysis, but also leads to a decline in the quality of life of patients; the increased expression of FAP, DDR2, and ILK in fibrotic peritoneum provides histological evidence for the PET imaging results. The upregulated expression of these molecules is closely related to the occurrence and development of peritoneal fibrosis, further confirming their potential as biomarkers of peritoneal fibrosis; Expression of FAP and Merge (immunofluorescence) and statistical analysis results, expression of FAP and Merge: statistical differences between the short dialysis age group, the long dialysis age group and the control group, indicating that the expression level of FAP increased with the increase in the degree of peritoneal fibrosis, this finding supports the reliability of FAP as a biomarker of peritoneal fibrosis; transport function and ultrafiltration capacity: the creatinine clearance rate of patients in the short dialysis age group and the long dialysis age group was higher than that in the control group, and the water ultrafiltration was lower; supporting the potential of these molecules as biomarkers of peritoneal fibrosis.

[0048] Control group subjects 68 Ga-FAPI PET images after development, the control group subjects received 68 No adverse reactions occurred after Ga-FAPI PET development, which indicates that the tracer is safe in humans and provides important evidence for its application in clinical diagnosis and treatment monitoring. 68 The high sensitivity and specificity of the Ga-FAPI PET tracer, as well as its good safety profile in humans, make it an important tool for assessing the extent of peritoneal fibrosis, monitoring disease progression, and guiding treatment decisions.

[0049] 68 Ga-labeled FAPI, DDR2, and ILK PET imaging have shown good application prospects in the assessment of peritoneal fibrosis. By quantifying the expression level and progression of target molecules and monitoring the therapeutic effect, these tracers provide strong support for the precise diagnosis and treatment of peritoneal fibrosis. At the same time, their good safety also lays a solid foundation for their wide application in clinical practice.

[0050] 4. Statistical Analysis Variance analysis was used to compare the differences between the experimental group and the control group. Pearson correlation analysis was performed between the SUV values ​​of PET and the results of the traditional peritoneal balance experiment. Receiver operating characteristic (ROC) curves of single-molecule and multi-molecule PET tracers were established to compare the sensitivity and accuracy of single-molecule and multi-molecule PET tracers.

[0051] The above contents are only for explaining the technical idea of ​​the present invention and cannot be used to limit the protection scope of the present invention. Any changes made on the basis of the technical solution in accordance with the technical idea proposed by the present invention shall fall within the protection scope of the claims of the present invention.

Claims

1. Application of a Ga-labeled PET tracer for peritoneal fibrosis marker in the preparation of a product for early diagnosis and progression monitoring of peritoneal fibrosis associated with peritoneal dialysis.

2. The use according to claim 1, characterized in that: The Ga-labeled peritoneal fibrosis marker PET tracer is formed by coupling Ga with a ligand or antibody of the peritoneal fibrosis marker.

3. The use according to claim 2, characterized in that: The peritoneal fibrosis marker is selected from at least one of fibroblast activation protein, discoidin domain receptor 2 and integrin linked kinase.

4. The use according to claim 1, characterized in that: The product for peritoneal fibrosis diagnosis is a PET imaging agent, a radiopharmaceutical preparation or a kit for in vitro diagnosis.

5. A Ga-labeled PET tracer for peritoneal fibrosis markers, characterized in that: The invention is composed of Ga coupled with a ligand or antibody of at least one peritoneal fibrosis marker selected from fibroblast activation protein, discoidin domain receptor 2 and integrin-linked kinase, and is used for tracking and imaging the location and extent of peritoneal fibrosis associated with peritoneal dialysis.

6. A PET diagnostic kit for detecting peritoneal fibrosis associated with peritoneal dialysis, characterized in that: The PET diagnostic kit comprises the Ga-labeled peritoneal fibrosis marker PET tracer of claim 5.

7. The PET diagnostic kit for detecting peritoneal fibrosis associated with peritoneal dialysis according to claim 6, characterized in that: The PET diagnostic kit also includes reagents and auxiliary tools for preparing PET tracers.

8. The PET diagnostic kit for detecting peritoneal fibrosis associated with peritoneal dialysis according to claim 7, characterized in that: The PET diagnostic kit also includes a buffer and a stabilizer for purification of the PET tracer.

9. The PET diagnostic kit for detecting peritoneal fibrosis associated with peritoneal dialysis according to claim 7, characterized in that: The PET diagnostic kit also includes software tools for PET image analysis.

10. A non-invasive detection method for peritoneal dialysis-related peritoneal fibrosis based on PET for non-disease diagnosis and treatment, characterized in that: Based on the Ga-labeled peritoneal fibrosis marker PET tracer of claim 5, PET imaging is used to evaluate the degree of fibrosis according to the SUV value of the imaging results.

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