A compound, a radionuclide label of the compound and a probe prepared therefrom

Abstract

The application discloses a compound, a radionuclide label of the compound and a prepared probe thereof, and belongs to the chemical field. 68 Ga-MGal can be used as a detection probe for recognizing beta-galactosidase, and is used for detecting the distribution of beta-galactosidase in a tissue organ. Those skilled in the art know that beta-galactosidase is a classic marker of cell aging, and therefore, the detection probe can judge the aging degree of the tissue organ by detecting the content of beta-galactosidase. Those skilled in the art also know that cell aging is also common in diseases such as cancer and fibrosis, and therefore, the detection probe can also judge the occurrence, development or prognosis state of the disease by detecting the content of beta-galactosidase.

Description

Technical Field

[0001] This invention belongs to the field of chemistry, specifically relating to a compound, a radionuclide label of the compound, and a probe prepared therefrom. Background Technology

[0002] Cellular senescence is caused by DNA damage, telomere shortening and dysfunction, carcinogenicity, and other types of cellular stress, and is a permanent arrest of the cell cycle process.

[0003] Previous studies have shown that cellular senescence triggered by tissue damage can induce chronic kidney disease (CKD) and fibrosis by activating DNA damage responses (such as the Chk2 / p53 pathway) and oxidative stress. Renal fibrosis is the ultimate common pathway of CKD, and the pathological accumulation of senescent cells (SnCs) is a key driver of its progression. However, renal fibrosis is not easily detected non-invasively, and real-time tracking of senescent cells remains technically challenging.

[0004] Cellular senescence plays a crucial role in cancer, functioning as both a tumor suppressor and a tumor promoter. Senescent cells undergo stable cell cycle arrest in response to various stressors, including DNA damage and oncogenic signaling, and exhibit a complex secretory phenotype known as the senescence-associated secretory phenotype (SASP), which influences the tumor microenvironment. Markers of senescence include cell cycle arrest, secretion of pro-inflammatory factors, structural changes, and metabolic alterations. While these characteristics initially suppress tumorigenesis, they can later contribute to cancer progression in certain situations.

[0005] Methods for studying aging in preclinical models include in vitro assays, ex vivo tissue analysis, and in vivo detection techniques. Emerging therapeutic strategies focus on leveraging aging for cancer treatment, particularly through the use of aging agents that selectively eliminate senescent cells and aging compounds that modulate SASP activity.

[0006] β-galactosidase (SA-β-gal or β-gal for short) is a glycoside hydrolase that is highly expressed and abnormally accumulated in senescent cells. In particular, the activity of senescence-related β-galactosidase in lysosomes is significantly increased, and it is widely regarded as a classic marker of cellular senescence.

[0007] In recent years, probe technologies based on β-gal activity have become a research hotspot due to their high sensitivity, real-time performance, and high throughput potential. Commonly used detection methods include colorimetry, electrochemistry, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). Imaging can be used to detect β-galactosidases, such as NIR-BG2, DDAOG, and Egad. 18F]FPyGal. However, existing galactosidase probes generally suffer from drawbacks such as difficult preparation, low selectivity, severe background signal interference, and poor photostability of fluorophores.

[0008] Early dynamic monitoring of cellular senescence not only facilitates the timely detection, diagnosis, and personalized treatment of aging-related diseases, but also provides key insights and new targets for understanding the biological mechanisms of aging and anti-aging interventions. Therefore, developing novel probes with high sensitivity and strong anti-interference capabilities for detecting senescent cells is of great significance. The inventors' team previously disclosed a detection probe for recognizing β-galactosidase and its application (Novel PET Imaging Probe for Quantitative Detection of Senescence In Vivo. Journal of Medicinal Chemistry. 2024). The chemical structure of this probe is as follows:

[0009] .

[0010] During in vivo imaging, probes, as foreign substances, will inevitably interfere with or cause side effects to the body. To reduce such interference or side effects, it is necessary to develop probes that are more strongly taken up by cells or tissues with high β-galactosidase expression, and less strongly taken up by normal tissues such as the kidneys.

[0011] Based on the above situation, the inventors' team has improved and developed a new probe, and hereby proposes this invention. Summary of the Invention

[0012] The present invention aims to overcome the shortcomings of the prior art and provide a compound, a radionuclide label of the compound, and a probe prepared therefrom.

[0013] The above-mentioned objective of this invention is achieved through the following technical solution:

[0014] A compound with the following chemical structural formula:

[0015] .

[0016] The radionuclide labeling of the above compounds.

[0017] Preferably, the radionuclide is selected from... 68 Ga、 18 F, 125 I, 131 I, 64 Cu、 67 Ga、 89 Zr、 86 Y、 90 Y、 99mTc, 111 In、 153 Sm、 177 Lu、 186 Re、 188 Re、 211 At、 212 Pb, 223 Ra and 225 One or more of Ac; more preferably, the radionuclide is 68 Ga.

[0018] The aforementioned radionuclide labels are used to prepare detection probes for recognizing β-galactosidase in vitro or in vivo. (The text then repeats the information about radionuclide labels.) 68 For example, Ga-labeled substances are specific to active β-galactosidase and can be used as detection probes to identify β-galactosidase.

[0019] The aforementioned radionuclide labels are used to prepare imaging probes for detecting the distribution of β-galactosidase in vitro or in vivo. (The text then repeats the information about radionuclide labels.) 68 For example, Ga-labeled substances are specific to active β-galactosidase and can be used as imaging probes to detect the distribution of β-galactosidase.

[0020] The aforementioned radionuclide labels are used to prepare imaging probes for assessing the degree of aging in tissues and organs by detecting β-galactosidase levels. (The text then repeats the information about radionuclides.) 68 Taking Ga-labeled substances as an example, cells with high β-galactosidase expression show more significant uptake of them compared to cells with normal β-galactosidase expression; in one specific embodiment, a radionuclide... 68 Ga markers can be used to determine the degree of aging in D-galactose-induced aging mice by detecting the activity of β-galactase in various organs.

[0021] The aforementioned radionuclide markers are used to prepare imaging probes that determine the occurrence, progression, or prognosis of a disease by detecting β-galactosidase levels. (The text then repeats the information about radionuclides.) 68 Taking Ga-labeled substances as an example, cells with high β-galactosidase expression show more significant uptake of them compared to cells with normal β-galactosidase expression; senescent cells with high β-galactosidase expression are commonly found in diseases such as cancer and fibrosis. Therefore, this radionuclide... 68 Ga markers can be used to determine the occurrence, development, or prognosis of a disease by detecting β-galactosidase levels.

[0022] Preferably, the disease is a tumor.

[0023] More preferably, the tumor is breast cancer, melanoma, gastric cancer, lung cancer, liver cancer, pancreatic cancer, cervical cancer, or colon cancer.

[0024] Preferably, the disease is renal fibrosis, liver fibrosis, pulmonary fibrosis, chronic kidney disease, cartilage aging, or osteoporosis.

[0025] Beneficial effects:

[0026] 1. This invention provides a novel compound MGal, and a radionuclide labeling of this compound. 68 Ga-MGal can be used as a detection probe to identify β-galactosidase and detect its distribution in tissues and organs. Those skilled in the art know that β-galactosidase is a classic marker of cellular senescence; therefore, this detection probe can determine the degree of aging in tissues and organs by detecting β-galactosidase levels. Those skilled in the art also know that cellular senescence is prevalent in diseases such as cancer and fibrosis; therefore, this detection probe can also determine the occurrence, development, or prognosis of diseases by detecting β-galactosidase levels.

[0027] 2. The inventors' team previously disclosed a detection probe for identifying β-galactosidase ( 68 Ga-BGal) and its applications (see Background Art). This is related to the already disclosed... 68 Compared to Ga-BGal, this invention 68 Although Ga-MGal differs from it by only one -CHF2, 68 Ga-MGal has two advantages:

[0028] (1) Cells with high expression of β-galactosidase 68 Ga-MGal uptake levels were significantly higher: In Example 3 of this invention, comparative experiments showed that cells with high β-galactosidase expression showed significantly higher uptake levels. 68 The intake level of Ga-MGal can actually reach the level of... 68 The Ga-BGal uptake level was 1.58 times higher, which makes it possible to reduce the amount of probe used.

[0029] (2) Normal kidney tissue against 68 Ga-MGal uptake levels were significantly lower: In Example 5 of this invention, comparative experiments showed that... 68 The uptake of Ga-MGal in normal kidney tissue is far lower than that in normal kidney tissue. 68 Ga-BGal can effectively reduce the side effects of the probe on normal kidney tissue;

[0030] Those skilled in the art will know that compounds with the same parent nucleus but only minor differences in substituents usually have similar activities. However, the compound for which protection is sought in this invention has significant advantages over previously disclosed compounds. The technical effects brought about by this minor structural improvement are difficult for those skilled in the art to predict. Attached Figure Description

[0031] Figure 1 The HPLC results for MGal are shown below.

[0032] Figure 2 High-resolution mass spectrometry for MGal;

[0033] Figure 3 The 1H NMR spectrum of MGal;

[0034] Figure 4 for 68 HPLC results of Ga-MGal;

[0035] Figure 5 The middle left image is 68 PET images of Ga-MGal incubated with β-Gal, inactivated β-Gal, fetal bovine serum, and phosphate buffer for 1 hour; the middle image is... 68 PET images of Ga-MGal and β-Gal incubated for 1, 5, 15, 30, and 60 min; the right image is... 68 PET images of Ga-MGal after incubation with different concentrations of β-Gal;

[0036] Figure 6 X-Gal staining results for CT26.CL25 and CT26.WT cells;

[0037] Figure 7 'a' is 68 The radioactive uptake values ​​of Ga-MGal at different time points after incubation with CT26.CL25 and CT26.WT cells with or without β-Gal; b represents the radioactive uptake values ​​of CT26.CL25 and CT26.WT cells after pre-incubation with 1 μg D-Gal for 30 minutes, followed by the addition of... 68 Radioactive uptake values ​​at different time points during Ga-MGal incubation; c represents the relevant quantitative analysis in Figures a and b;

[0038] Figure 8 'a' is 68 Ga-MGal and 68 Radioactive uptake values ​​of Ga-BGal and CT26.CL25 cells at different time points during incubation; b represents the radioactive uptake values ​​of Ga-BGal and CT26.CL25 cells at different time points; 68 Ga-MGal and 68 Quantitative analysis of radioactive uptake values ​​of Ga-BGal and CT26.CL25 cells after 4 hours of incubation;

[0039] Figure 9 For injection 68 Anatomical biodistribution of the control group and the D-Gal treatment group 4 h after Ga-MGal treatment;

[0040] Figure 10 PET / CT images and X-Gal staining results of mice in the control and experimental groups at different time points;

[0041] Figure 11 CT26.CL25 and CT26.WT tumor-bearing mice were injected with... 68 Ga-MGal and 68 PET / CT images at different time points after Ga-BGal;

[0042] Figure 12 CT26.CL25 and CT26.WT tumor-bearing mice were injected with... 68 Ga-MGal and 68 Quantitative analysis of renal uptake values ​​at different time points after Ga-BGal;

[0043] Figure 13 For injection 68 PET / CT images of control mice and folic acid-treated mice at different time points after Ga-MGal treatment;

[0044] Figure 14 For injection 68 Anatomical biodistribution of the control group and folic acid treatment group 4 hours after Ga-MGal administration. Detailed Implementation

[0045] The substantive content of the present invention will be described in detail below with reference to specific embodiments. However, those skilled in the art should know that the scope of protection of the present invention should not be limited to these specific embodiments.

[0046] Example 1: Compound MGal, radionuclide labeling 68 Preparation of Ga-MGal

[0047] ;

[0048] Compound 1 was first dissolved in a DMF / NEt3 (volume ratio 10:1) mixed solvent, and then added to a DMF solution (1 equivalent) of p-SCN-Bn-NOTA. The mixture was stirred at room temperature for 3 hours. Subsequently, the reaction was monitored and purified by high-performance liquid chromatography (HPLC). The purified sample was then analyzed by liquid chromatography (HPLC), mass spectrometry (MS), and nuclear magnetic resonance (NMR). 1H NMR (600MHz, D2O) δ 7.59 (s, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.32 (m, 5H), 7.14 (t, J =55.2 Hz, 1H), 5.12 (d, J = 7.2 Hz, 1H), 4.02 (d, J = 3.0 Hz, 1H), 3.98–3.74(m, 9H), 3.66–2.95 (m, 13H), 2.90–2.82 (m, 1H), 2.73 (s, 1H). Figure 1 The results are from the HPLC analysis of compound MGal. Figure 2 MS detection results for compound MGal; Figure 3 For the compound MGal 1 1H NMR detection results.

[0049] Radionuclide markers 68 Preparation of Ga-MGal:

[0050] First, use 5 ml of 0.1 mol / L (M) hydrochloric acid (HCl) to... 68 GaCl3 (185-370 MBq) from 68 Ge- 68 In a Ga generator (ITM Isotope Technologies GmbH, Munich, Germany), the solution was eluted into a reaction flask and then diluted with sodium acetate buffer (1.0 mol / L, pH 5.0). Subsequently, 10 μg of MGal solution (1 μg / μL in ultrapure water) was added to the reaction flask, and the pH of the resulting mixture was monitored to ensure it was within the range of 4.5–5.0. The mixture was incubated at 37°C for 10 minutes, and the labeling yield, purity, and stability were determined by HPLC. Before use, the solution was filtered through a 0.22 μm filter into sterile vials, and then aliquoted into multiple vials for cell experiments or in vivo studies.

[0051] Figure 4 Radionuclide markers 68 HPLC detection results of Ga-MGal.

[0052] Example 2: 68 Ga-MGal's specificity (at the molecular level) for active β-galactosidase (β-Gal)

[0053] 1. Test Methods

[0054] The recombinant β-Gal protein was dissolved and diluted to different concentrations with PBS solution. The inactivation group was heated at 100℃ for 10 min to deactivate it. As a control, fetal bovine serum albumin (BSA) control and blank solution control (PBS) were prepared respectively. 68 Dilute Ga-MGal with physiological saline to 1 μCi / μL; immediately add 10 μL (10 μCi) of probe to each EP tube and incubate at 37°C for 30 min.

[0055] After incubation, add 5× protein loading buffer to each EP tube; heat all samples at 100℃ for 10 min, mix well, and add to the SDS-PAGE gel wells, adding an equal volume of 1× loading buffer between every two samples, leaving one well for adding pre-stained protein marker; after loading, perform electrophoresis at a constant voltage of 150 V. After electrophoresis, rinse the glass plate with water and place it on a plate for PET / CT static scanning for 10 min.

[0056] 2. Test Results

[0057] Gel electrophoresis is used for research 68 The interaction between Ga-MGal and β-Gal. For example... Figure 5 As shown, in the presence of active β-galactosidase, 68 A radioactive uptake signal was observed at approximately 25 kDa after Ga-MGal incubation. This signal was not observed at approximately 25 kDa in the inactivated β-galactosidase and BSA / PBS controls, demonstrating that... 68 Ga-MGal exhibits specificity for active β-Gal (left figure). Meanwhile, the intensity of the radioactive signal gradually increases with prolonged incubation time (middle figure) or higher protein concentration (right figure).

[0058] Example 3: Cells with high β-galactosidase expression 68 Ga-MGal uptake levels (cellular level)

[0059] 1. Cell Culture

[0060] All cell lines were purchased from the American Type Culture Collection (ATCC).

[0061] CT26.CL25 (used for expressing β-galactosidase) LacZThe encoded CT26 cell line (highly expressing β-galactosidase) and CT26.WT (mouse colon cancer cells, control) were cultured in RPMI-1640 medium (Gibco, C11875500BT) containing 10% FBS (Excell, FSP500) and 1% penicillin-streptomycin (Gibco, 15070063) under humidified conditions of 37°C and 5% CO2. X-Gal staining was used to verify β-galactosidase expression in the cells.

[0062] Assessing cell response 68 Ga-MGal (prepared in Example 1) 68 Ga-BGal (previously prepared and disclosed by the inventors, see Background Art) uptake capacity:

[0063] a. 1×10 6 CT26.CL25 and CT26.WT cells were seeded in 6-well plates and incubated overnight.

[0064] b. Aspirate the culture medium, wash once with PBS, add HANKS HEPES buffer, and then add 0.37 MBq at different time points (0.5 h, 1 h, 2 h, 4 h). 68 Ga-MGal or 68 Ga-BGal was incubated with cells;

[0065] c. Wash three times with pre-cooled PBS immediately after incubation;

[0066] d. Lyse cells with RIPA lysis buffer, collect the lysis buffer, and determine protein concentration;

[0067] e. The cell lysate and probe standard (0.37 MBq) were measured using a gamma counter, and the radioactivity count and time were recorded;

[0068] f. After attenuation correction and conversion to reference standards for the radioactive count, the probe cell uptake rate (%ID / mg) was calculated. The uptake of the probe by CT26.CL25 and CT26.WT cells and the changes in uptake rate over time were analyzed to determine the probe binding specificity and probe distribution ability.

[0069] 2. Test Results

[0070] like Figure 6 As shown, β-galactosidase is highly expressed in CT26.CL25 cells, which is consistent with the cell characteristics.

[0071] like Figure 7 As shown, probe uptake in CT26.CL25 cells was significantly higher than that in CT26.WT cells ( Figure 7(a, c), and the intake is time-dependent ( Figure 7 (a) At 4 hours, CT26.CL25 cells and CT26.WT cells showed differences in resistance to... 68 The uptake of Ga-MGal was 4.7 ± 0.37% ID / mg and 2.2 ± 0.36% ID / mg, respectively. Before adding 1 μg of recombinant β-galactosidase to the culture medium, add... 68 During Ga-MGal, CT26.WT and CT26.CL25 cells 68 Ga-MGal intake will decrease ( Figure 7 (a, c); after pre-incubation with 5 mmol of the β-galactosidase specific inhibitor D-galactose (D-Gal) for 30 minutes, the following were added 68 After Ga-MGal treatment for 0.5, 1, 2, and 4 hours, the intake at all time points was lower than that in the group without supplementation. Figure 7 b, and combined Figure 7 (a)

[0072] like Figure 8 As shown in Figures a and b, CT26.CL25 cells... 68 Ga-MGal intake was significantly higher than that of... 68 Ga-BGal uptake, at 4 hours, CT26.CL25 cells showed [response to] 68 Ga-MGal, 68 The intakes of Ga-BGal were 4.7 ± 0.37 %ID / mg and 2.97 ± 0.20 %ID / mg, respectively.

[0073] Those skilled in the art know that 68 Ga-MGal and 68 Ga-BGal differs from each other by only one -CHF2 group, and should normally have similar activities, but cells with high β-galactosidase expression show different responses to... 68 The intake level of Ga-MGal can actually reach the level of... 68 It was 1.58 times the level of Ga-BGal intake.

[0074] Example 4: In vivo PET / CT imaging of an aging model (animal level)

[0075] A drug-induced aging model was established using 6-week-old BALB / c mice for in vivo imaging. After one week of stabilization, mice were injected daily via tail vein with 300 mg / kg of D-galactose. Control mice received an equal volume of saline daily via tail vein. Mice in both groups were injected via tail vein at weeks 1, 3, and 5 after D-galactose administration. 68PET imaging was performed using Ga-MGal (3.7 MBq).

[0076] All PET images were reconstructed using PMOD 4.302 software (PMOD Technologies, Switzerland), and further analysis was performed on the major tissues and organs. 68 Intake of Ga-MGal.

[0077] The liver and kidneys of mice in the aging model group (D-Gal-treated) showed the most significant aging, therefore Figure 9 It can be seen that the liver and kidneys of the aging model group mice have a significant effect on... 68 The uptake of Ga-MGal was significantly higher in mice than in the control group (Saline-treated) mice.

[0078] Figure 10 The signal distribution of PET / CT imaging and the results of X-Gal staining of the kidneys were compared at different time points (1, 3, and 5 weeks). In week 1, the PET signal distribution was similar in the aging model group and the control group, and X-Gal staining of the kidneys was negative. In week 3, PET images showed that the kidney uptake in the aging model group was higher than that in the control group, and X-Gal staining of the kidneys showed partial positivity. In week 5, the kidney uptake in the aging model group was significantly higher, and X-Gal staining showed a clear positivity.

[0079] The experimental results fully demonstrate that 68 Ga-MGal can determine the degree of aging in D-galactose-induced aging mice by detecting the activity of β-galactase in various organs.

[0080] Example 5: In vivo PET / CT imaging of a tumor model (animal level)

[0081] 1. Animal models

[0082] All animal experiments were conducted in accordance with the guidelines (No.: 2022-071) of the Animal Care and Use Committee of the Animal Resource Department, Xiangya Second Hospital, Central South University. CT26.WT and CT26.CL25 cells (1×10⁻⁶) were used. 5 One cell was subcutaneously injected into the left forelimb of female BALB / c mice with 100 μL of phosphate-buffered saline solution (PBS, Gibco, C10010500BT). In vivo PET imaging experiments were performed on the mice when the tumor volume reached 300 mm³ (1-2 weeks after inoculation).

[0083] 2. PET / CT scan

[0084] Mice were anesthetized with isoflurane and placed on a PET / CT scanner (Super Nova PET / CT, PINGSENG). During PET / CT imaging, mice were intravenously injected with 3.7 MBq. 68 Ga-MGal or 68 Ga-BGal (n=3). Image acquisition began immediately after injection, with 1 hour of dynamic PET imaging and 2 and 4 hours of static PET scans performed. All PET images were reconstructed using PMOD 4.302 software (PMOD Technologies, Switzerland) and further analyzed for tumors and other tissues of interest.

[0085] 3. Test Results

[0086] like Figure 11 As shown, the CT26.CL25 tumor was injected with... 68 Ga-MGal, 68 Significant uptake was observed at 0.5, 1, 2, and 4 hours after Ga-BGal administration, with marked contrast compared to healthy tissue. Simultaneously, it was clearly evident that… 68 Ga-MGal uptake in tumors is far higher than 68 Ga-BGal.

[0087] Dynamic and delayed static imaging revealed similar biodistribution patterns in normal organs for both groups. Significant signals were observed in the liver, kidneys, and bladder, indicating that the probes were primarily cleared via the urinary system, with partial clearance via the hepatobiliary system. It is particularly important to emphasize that... Figure 12 It can be seen that, 68 The uptake of Ga-MGal by the kidneys is far lower than 68 Ga-BGal can effectively reduce the side effects of the probe on normal kidneys.

[0088] Example 6: In vivo PET / CT imaging (animal level) of a folic acid-induced renal fibrosis model

[0089] 1. Animal models

[0090] To induce renal fibrosis, C57BL / 6 mice (8 weeks old) were intraperitoneally injected with 0.2 mL of folic acid (FA, 250 mg / kg) dissolved in 0.3 mol / L NaHCO3 for 14 consecutive days. At this dose, folic acid administration led to severe nephrotoxicity and renal fibrosis. A solvent control (NaHCO3) was also included.

[0091] 2. PET / CT scan

[0092] Mice were anesthetized with isoflurane and placed on a PET / CT scanner (Super Nova PET / CT, PINGSENG). During PET / CT imaging, mice were intravenously injected with 3.7 MBq. 68 Ga-MGal (n=3). Image acquisition began immediately after injection, with 1 hour of dynamic PET imaging and 2 and 4 hours of static PET scans performed. All PET images were reconstructed using PMOD 4.302 software (PMOD Technologies, Switzerland) and further analyzed for the kidneys and other tissues of interest.

[0093] 3. Test Results

[0094] like Figure 13 As shown, the kidneys of the folic acid-treated group exhibited strong signal values ​​at 0.5, 1, and 2 hours, significantly higher than those of the NaHCO3-treated control group. Quantitative analysis of the PET data indicated that tracer uptake in the kidneys of the folic acid-treated group gradually increased after tracer injection, peaking at 13.73 ± 1.18 %ID / g at 1 hour, significantly higher than that of the control group. Figure 14 As shown, apart from the kidneys, there were no significant differences in uptake values ​​for other major organs between the two groups.

[0095] In summary:

[0096] This invention provides a novel compound MGal, and a radiolabeled version of this compound. 68 Ga-MGal can be used as a detection probe to identify β-galactosidase and detect its distribution in tissues and organs. Those skilled in the art know that β-galactosidase is a classic marker of cellular senescence; therefore, this detection probe can determine the degree of aging in tissues and organs by detecting β-galactosidase levels. Those skilled in the art also know that cellular senescence is prevalent in diseases such as cancer and fibrosis; therefore, this detection probe can also determine the occurrence, development, or prognosis of diseases by detecting β-galactosidase levels.

[0097] The purpose of the above embodiments is to specifically illustrate the substantive content of the present invention, but those skilled in the art should know that the scope of protection of the present invention should not be limited to the specific embodiments.

Claims

1. A radionuclide label for a compound with the following structure, wherein the radionuclide is... 68 Ga: 。 2. The use of the radionuclide label of claim 1 for preparing imaging probes that determine the degree of aging of tissues and organs by detecting the content of β-galactosidase.

3. The use of the radionuclide label of claim 1 for preparing imaging probes that determine the occurrence, development or prognosis of a disease by detecting the content of β-galactosidase.

4. The use according to claim 3, characterized in that: The disease in question is a tumor.

5. The use according to claim 4, characterized in that: The tumor is breast cancer, melanoma, stomach cancer, lung cancer, liver cancer, pancreatic cancer, cervical cancer, or colon cancer.

6. The use according to claim 3, characterized in that: The diseases mentioned are renal fibrosis, liver fibrosis, pulmonary fibrosis, chronic kidney disease, cartilage aging, or osteoporosis.

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