Radionuclide molecular imaging agent, preparation method and application thereof
By preparing 18F-labeled TD-1 compounds as radionuclide molecular imaging agents, the problem of difficulty in identifying early thrombosis and vulnerable plaques in existing technologies has been solved, achieving efficient and specific targeted imaging and supporting the accurate diagnosis of thrombosis and atherosclerosis.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- 李剑明
- Filing Date
- 2026-03-18
- Publication Date
- 2026-07-14
AI Technical Summary
Existing non-invasive imaging techniques are insufficient to accurately identify early thrombosis or vulnerable plaques. Clinically, there is a lack of highly effective radioactive imaging agents that target GPIIb/IIIa receptors, leading to difficulties in diagnosing thrombosis and atherosclerotic diseases.
An 18F-labeled TD-1 compound (18F-TD-1) was developed as a radioactive molecular imaging agent. It was prepared by reacting Cu(Py)4(OTf)2 in DMA solvent using a multi-step synthesis and semi-preparative HPLC separation method to generate 18F-TD-1 with high radiochemical purity.
It achieves high affinity and specificity imaging of GPIIb/IIIa receptors, provides high-contrast PET imaging, supports accurate diagnosis and lesion localization of thrombosis and atherosclerotic plaques, and has high radiochemical yield and in vitro and in vivo stability.
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Figure CN122381007A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of nuclear medicine imaging and radiopharmaceutical technology, and in particular to a radionuclide molecular imaging agent, its preparation method and application. Background Technology
[0002] Thrombotic diseases (such as deep vein thrombosis and pulmonary embolism) and cardiovascular and cerebrovascular events caused by atherosclerotic plaques and their rupture (such as myocardial infarction and stroke) are major diseases that seriously endanger human health. Early, accurate, and non-invasive diagnosis and risk assessment of these diseases are crucial for clinical treatment decisions and prognosis improvement.
[0003] Currently, commonly used non-invasive imaging techniques in clinical practice include ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). However, these techniques mainly rely on morphological changes, and their sensitivity and specificity are limited in identifying early, unstable thrombi or vulnerable plaques, making it difficult to accurately assess their activity and thrombosis risk.
[0004] Nuclear medicine molecular imaging techniques, particularly positron emission tomography (PET), can achieve in vivo imaging at the physiological or pathochemical level using molecular probes that specifically target pathological processes, providing a powerful tool for the early and accurate diagnosis of these diseases. Among these, designing radioactive imaging agents targeting the glycoprotein GPIIb / IIIa receptor (integrin αIIbβ3), which is highly expressed on the platelet membrane surface, is an effective strategy for achieving specific imaging of thrombi or activated platelet-related plaques. Previous studies have explored the use of... 18 F, 68 Ga and other radionuclide-labeled RGD series peptides or other small molecule antagonists serve as imaging agents targeting GPIIb / IIIa integrin receptors.
[0005] However, there is a severe shortage of GPIIb / IIIa-targeting imaging agents used clinically for thrombosis detection. Therefore, the development of a one-step, highly efficient method for detecting GPIIb / IIIa receptors is crucial. 18 F-labeled nuclear medicine imaging agents with excellent targeting properties are of great clinical significance and application value in promoting the accurate diagnosis of thrombosis and atherosclerosis-related diseases. Summary of the Invention
[0006] The technical problem to be solved by the present invention is to provide a radioactive nuclide molecular imaging agent.
[0007] Another technical problem to be solved by the present invention is to provide a method for preparing the above-mentioned radioactive nuclide molecular imaging agent.
[0008] Another technical problem to be solved by the present invention is to provide the application of the above-mentioned radionuclide molecular imaging agent.
[0009] The technical solution adopted in this invention is: A radioactive nuclide molecular imaging agent, the structure of which is shown in formula (I). 18 F-labeled TD-1 compound ( 18 F-TD-1 or its pharmaceutically acceptable salt .
[0010] The aforementioned radionuclide molecular imaging agent, wherein 18 F is introduced into the TD-1 compound by forming a CF bond on the aromatic ring.
[0011] A method for synthesizing the above 18 The precursor compound of the F-labeled TD-1 compound has the structure shown in formula (II). .
[0012] The above-mentioned method for preparing radioactive nuclide molecular imaging agents involves reacting the precursor compound of formula (II) with... 18 F ions react in DMA solvent at 120°C under Cu(Py)4(OTf)2 catalysis to generate the compound of formula (I).
[0013] Preferably, the preparation method of the above-mentioned radionuclide molecular imaging agent involves using dry K... 18 The precursor compound of formula (II), Cu(Py)4(OTf)2, and DMA were added to the DMA solution of F, and the mixture was heated at 120°C for 20 minutes. After cooling, HI solution was added, and the protecting group was removed by heating. After cooling, NaOH solution was added for neutralization, and the product was separated by semi-preparative HPLC to obtain the target product. 18 F-TD-1; Target product analyzed by radio-HPLC 18 F-TD-1 has a radiochemical purity greater than 99%.
[0014] Preferably, the preparation method of the above-mentioned radionuclide molecular imaging agent includes the following specific steps: (1) 4-(4-hydroxybutyl)piperidine-1-carboxylic acid tert-butyl ester, carbon tetrabromide, dichloromethane and triphenylphosphine were reacted at room temperature, and then the mixture was distilled under reduced pressure and subjected to rapid column chromatography to obtain compound 2; (2) Compound 2, sodium iodide, cesium carbonate and ((benzyloxy)carbonyl)-L-tyrosine tert-butyl ester were refluxed in acetonitrile, extracted with ethyl acetate, and then subjected to rapid column chromatography to obtain compound 3; (3) Compound 3 was reacted with hydrogen in methanol using Pd / C as a catalyst. After the reaction was complete, the mixture was filtered and evaporated to dryness to obtain compound 4; (4) Compound 4 reacted with 4-iodobenzenesulfonyl chloride in dichloromethane, was extracted and separated, and purified by rapid column chromatography to obtain compound 5; (5) Compound 5, hexamethyldistin and tetra(triphenylphosphine)palladium were heated and reacted in 1,4-dioxane. After filtration and extraction, compound 6 was purified by rapid column chromatography.
[0015] The synthetic route for preparing the above-mentioned radioactive nuclide molecular imaging agent is as follows:
[0016] A method for comparison with the above 18 The standard compound (TD-1) of the F-labeled TD-1 compound has the structure shown in formula (Ⅲ). .
[0017] The specific steps for preparing the above-mentioned standard compounds are as follows: 1) Compound 4 reacted with 4-fluorobenzenesulfonyl chloride at room temperature, and then compound 7 was obtained by rapid column chromatography; 2) After reacting compound 7 obtained in step 1) with trifluoroacetic acid in dichloromethane, the mixture was distilled under reduced pressure and subjected to rapid column chromatography to obtain compound 8.
[0018] The synthetic route for preparing the above-mentioned standard compounds is as follows:
[0019] The aforementioned radionuclide molecular imaging agents are used to enhance medical imaging in the diagnosis of thrombosis or atherosclerotic plaques.
[0020] Preferably, in the above applications, the diagnosis is achieved through positron emission tomography (PET) or PET / CT imaging.
[0021] The application of the aforementioned radionuclide molecular imaging agents in molecular visualization imaging tools.
[0022] The beneficial effects of this invention are: The aforementioned radionuclide molecular imaging agents serve as PET molecular probes targeting GPIIb / IIIa receptors. 18 F-TD-1 is the positron-emitting nuclide fluorine-18 (F-TD-18) 18 F) labeled TD-1 compound ( 18 F-TD-1), through a one-step highly efficient copper catalysis 18Prepared via F-fluorination, this imaging agent exhibits high radiochemical yield, high specific activity, and good in vitro and in vivo stability. It demonstrates high affinity and specificity for GPIIb / IIIa receptors and excellent in vivo pharmacokinetic properties, enabling rapid, high-contrast radionuclide imaging of thrombosis or atherosclerotic plaques in various systems within in vivo models. This is characterized by rapid blood clearance and excellent signal-to-noise ratio. Therefore, this imaging agent can achieve high target-to-background ratio and high-contrast PET imaging in thrombosis or atherosclerotic plaque models, providing a real-time, non-invasive, and precise molecular visualization tool for the differential diagnosis of thrombotic diseases or atherosclerotic plaque-related diseases, precise lesion localization, systemic thrombotic burden assessment, and efficacy monitoring. Attached Figure Description
[0023] Figure 1 In Embodiment 9 of the present invention 18 HPLC chromatogram of F-TD-1 for quality control.
[0024] Figure 2 Compound 6 in Example 5 of this invention ( 18 F-TD-1 precursor) 1 H NMR spectrum.
[0025] Figure 3 Compound 6 in Example 5 of this invention ( 18 F-TD-1 precursor) 13 C10 NMR spectrum.
[0026] Figure 4 Compound 8 (TD-1 standard) in Example 7 of this invention 1 H NMR spectrum.
[0027] Figure 5 Compound 8 (TD-1 standard) in Example 7 of this invention 13 C10 NMR spectrum.
[0028] Figure 6 This is a PET-CT image of an animal in Embodiment 10 of the present invention. Detailed Implementation
[0029] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be further described in detail below with reference to specific embodiments.
[0030] Example 1 Synthesis of compound 2:
[0031] 4-(4-hydroxybutyl)piperidine-1-carboxylate tert-butyl ester (4 g, 15.6 mmol) and carbon tetrabromide (8.3 g, 25.12 mmol) were dissolved in dichloromethane (30 mL), and the solution was cooled to -5 °C (NaCl ice bath) under an argon atmosphere. A solution of triphenylphosphine (4.9 g, 18.84 mmol) in dichloromethane (15 mL) was slowly added dropwise to the stirred mixture to maintain the temperature of the mixture below 5 °C. The resulting solution was stirred at room temperature for 75 min. TLC showed completion. The solvent was removed under reduced pressure to give a yellow residue. The crude product was purified by rapid chromatography (elution: light petroleum / ethyl acetate / 90:10 v / v) to give 4-(4-bromobutyl)piperidine-1-carboxylate tert-butyl ester (compound 2).
[0032] 1 H NMR (400MHz, CDCl3) δ 4.08 (dt, J =13.2, 2.7 Hz, 2H), 3.42 (t, J =6.8Hz,2H),2.64-2.68(m,2H),1.85(dt, J =14.5,6.9Hz,2H),1.70-1.62(m,2H),1.52-1.43(m,11H),1.36-1.39(m,1H),1.31-1.22(m,2H),1.08(qd, J =12.5, 4.2 Hz, 2H).
[0033] Example 2 Synthesis of compound 3:
[0034] Compound 2 (3.2 g, 1.0 mmol), NaI (0.75 g, 0.5 mmol), Cs₂CO₃ (10 g, 3.0 mmol), and ((benzyloxy)carbonyl)-L-tyrosine tert-butyl ester (3.7 g, 1.0 mmol) described in Example 1 were dissolved in MeCN (50 mL), and the mixture was refluxed for 16 hours. The mixture was cooled to room temperature. The reaction mixture was poured into water (150 mL), and the reaction mixture was extracted with EtOAc (3 × 75 mL). The mixture was washed with brine (2 × 50 mL), and the combined organic layers were dried over anhydrous Na₂SO₄. The mixture was filtered to remove solids, and the mixture was evaporated to dryness. The crude product was purified by rapid column chromatography on silica using petroleum / EtOAc (90:10) to give compound 3.
[0035] 1H NMR (400MHz, CDCl3) δ7.43-7.31(m,5H),7.11-6.96(m,2H),6.86-6.72(m,2H),5.18-5.04(m,2H), 4.51(q, J =6.6Hz,1H),4.13-4.05(m,2H),3.94(t, J =6.4Hz,2H),3.04(dd, J =6.1,2.5Hz,2H),2.77-2.57(m,2H),1.77(dd, J =14.3,6.8Hz,3H),1.72-1.64(m,2H),1.46(d, J =16.4Hz,21H),1.35-1.26(m,3H),1.15-1.06(m,2H).
[0036] Example 3 Synthesis of compound 4:
[0037] Compound 3 (3.00 g, 50 mmol) from Example 2 was dissolved in anhydrous methanol (60 mL), and Pd / C (1 g, 10%) was added under hydrogen atmosphere. The mixture was stirred at room temperature for 2 hours. LC-MS showed completion. The mixture was filtered to remove solid Pd / C, and evaporated to dryness to give compound 4 (2.4 g, 100%) as a colorless oil.
[0038] 1 H NMR (400MHz, CDCl3) δ7.07-6.99(m,2H),6.81-6.71(m,2H),4.00(s,2H),3.86( t,J=6.5Hz,2H),3.50(dd,J=7.5,5.5Hz,1H),2.91(dd,J=13.8,5.5Hz,1H),2.73 (dd,J=13.7,7.5Hz,1H),2.60(t,J=12.3Hz,2H),1.68(p,J=6.7Hz,2H),1.59(d, J=13.1Hz,2H),1.37(d,J=5.8Hz,21H),1.25-1.19(m,2H),1.02(td,J=12.3,4.3 Hz,2H). 13C NMR (151MHz, CDCl3) δ173.91,158.00,154.94,130.41,129.02,114.50,81.39,79.20,67.84,56.22,39.88,36.10,29.45,28.49,28.04,23.16.
[0039] Example 4 Synthesis of compound 5:
[0040] To a 10 mL solution of compound 4 (0.3 g, 0.6 mmol) in ethyl acetate as described in Example 3, 4 mL of saturated sodium bicarbonate and 0.2 g, 0.72 mmol of 4-iodobenzenesulfonyl chloride were added. The mixture was stirred at room temperature for 8 hours. TLC showed completion. Extraction and separation were performed, and compound 5 was purified by rapid column chromatography.
[0041] 1 H NMR (400MHz, CDCl3) δ7.75-7.68(m,2H),7.41-7.35(m,2H),6.94(d,J=8.5H z,2H),6.69(d,J=8.6Hz,2H),5.00(d,J=9.4Hz,1H),4.03-3.92(m,3H),3.8 5(t,J=6.4Hz,2H),2.95-2.81(m,2H),2.65-2.56(m,2H),1.70(p,J=6.7Hz, 2H),1.59(d,J=12.9Hz,2H),1.38(s,11H),1.18(s,12H),1.06-0.97(m,2H).
[0042] Example 5 Synthesis of compound 6:
[0043] Under argon atmosphere, hexamethyldistin (0.2 g, 0.6 mmol) and tetra(triphenylphosphine)palladium (18 mg, 15 μmol, 5% equivalent) were added sequentially to a solution of anhydrous 1,4-dioxane (10 mL) of compound 5 (0.3 g, 0.4 mmol) pre-degassed by argon bubbling. The reaction mixture was refluxed for 10 hours. At this point, the reaction color deepened. After cooling to room temperature, the reaction mixture was filtered through a diatomaceous earth mat and washed with ethyl acetate (3 × 10 mL). The filtrate was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography, as follows: Figure 2 , Figure 3 As shown, compound 6 was obtained. 18F-TD-1 precursor is a colorless oily substance.
[0044] 1 H NMR (400MHz, DMSO) δ 8.12 (d, J =9.1Hz,1H),7.48-7.24(m,4H),6.82(d, J =8.6Hz,2H),6.57(d, J =8.6 Hz, 2H), 3.70(t, J =6.5Hz, 4H), 3.55(q, J =8.0Hz,1H),2.64-2.37(m,4H),1.52-1.35(m,4H),1.17(s,12H),1.03(d, J =6.7Hz,2H),0.87(s,9H),0.73(qd, J =12.3,4.2Hz,2H),0.07(s,9H). 13 C NMR (151 MHz, CDCl3) δ170.70,159.21,155.87,150.69,140.37,137.22,131.65,127.91,126.99,115.34,80.12,68.77,57.87,39.80,37.05(d, J =44.5Hz),30.38,29.43,28.64,24.10,8.61.
[0045] Example 6 Synthesis of compound 7:
[0046] To a solution of compound 4 (0.1 g 0.2 mmol) in ethyl acetate (10 mL), saturated sodium bicarbonate solution (4 mL) and 4-fluorobenzenesulfonyl chloride (0.1 g 0.5 mmol) were added. The mixture was stirred at room temperature for 8 hours. TLC showed completion. The liquid was separated and purified by column chromatography to give compound 7 (80 mg, 60%) as a colorless oil.
[0047] 1 H NMR (400MHz, CDCl3) δ7.71-7.66(m,2H),7.06-6.91(m,4H),6.70-6.66(m,2H),4.04-3.98(m,2H),3.83(t, J =6.4Hz,2H),2.92-2.81(m,2H),2.60(td, J=12.9,2.7Hz,2H),1.69(q, J =7.1Hz,2H),1.59(dd, J =13.5,3.4Hz,2H),1.38(s,11H),1.18(s,13H),1.06-0.96(m,2H).
[0048] Example 7 Synthesis of compound 8:
[0049] Under a nitrogen atmosphere, TFA (1 mL) was added to a solution of compound 7 (80 mg, 0.12 mmol) obtained in the previous step in dichloromethane (1 mL), and the mixture was stirred at room temperature for 2 h. LC-MS showed completion. The mixture was evaporated to dryness to give the crude product. The resulting residue was purified by semi-preparative HPLC using a reversed-phase C18 column, as follows: Figure 4 , Figure 5 As shown, compound 8 (TD-1 standard, 10 mg, 17%) was obtained as a white solid.
[0050] 1 H NMR(400MHz,DMSO)δ8.52(s,1H),8.33(d, J =9.1Hz,1H),8.22(s,1H),7.58(dd, J =8.6, 5.2 Hz, 2H), 7.22(t, J =8.7Hz,2H),7.01(d, J =8.2Hz,2H),6.71(d, J =8.2Hz,2H),3.90(t, J =6.4Hz,2H),3.80(dt, J =9.3,4.6Hz,1H),3.24(s,2H),2.92-2.80(m,3H),2.62(dd, J =13.7, 9.6 Hz, 1H), 1.81 (d, J =13.9Hz,2H),1.70(p, J =6.9Hz,2H),1.57-1.40(m,3H),1.37-1.14(m,6H).
[0051] Example 8 compound 18 Synthesis of F-TD-1: Bombarding the accelerator 18 F -Ions were captured on an anion exchange column and eluted into a reaction flask with a mixture containing potassium carbonate (1 mg), K222 (7.5 mg), acetonitrile (0.9 mL), and water (0.1 mL). The solution was dried at 110°C under a nitrogen stream, and then 1 mL of dry acetonitrile was added, followed by drying at 100°C under a nitrogen stream. A DMA solution (1 mL) containing Cu(Py)4(OTf)2 (10 mg) and TD-1 precursor (5 mg) was added, and the mixture was heated at 110°C for 20 minutes. After the reaction, 10% HI solution (1 mL) was added, and the mixture was heated at 100°C for 5 minutes. The reaction was then neutralized with 2M sodium hydroxide solution (1 mL). Separation was performed using semi-preparative HPLC. The collected liquid was diluted with 50 mL of high-purity water and loaded onto a Sep-pak C18 column. The Sep-pak C18 column was rinsed with 10 mL of water, and the liquid was transferred to waste liquid. A 0.2 μm sterile filter membrane was attached to the Sep-pak C18 column, and the Sep-pak C18 column was eluted with 1 mL of pharmaceutical ethanol to obtain the target product. 18 F-TD-1, then rinse the C18 column and sterile filter membrane with 5 mL of physiological saline into a sterile product bottle.
[0052] Example 9 compound 18 Quality control of F-TD-1: The above-obtained compound 18 F-TD-1 was analyzed by radio-HPLC under the following conditions: InertSustain C18 column (4.6×250mm, 5μm, Shimadzu-GL, Japan), mobile phase: 40% acetonitrile (0.1% TFA), flow rate: 1.0 ml / min. Figure 1 The results show 18 The radiochemical purity of F-TD-1 is greater than 99%.
[0053] Example 10 Model building Three adult beagles (14-16 kg, male or female) were selected and acclimatized for one week prior to the experiment, during which time their eating, drinking, and behavioral status were normal. On the day of the experiment, they were fasted for 8 hours and deprived of water for 4 hours. Basic sedation and restraint were achieved by intramuscular injection of celazine hydrochloride (3-5 mg / kg) combined with dexmedetomidine (3-5 μg / kg), followed by establishing access via the marginal ear vein or forelimb vein. Approximately 20 minutes later, propofol (0.2 mg / kg) was administered intravenously to maintain anesthesia (injection rate ≤10 mg / s), and atropine was administered prophylactically as needed based on vital signs.
[0054] Preparation of autologous thrombi: Tranexamic acid 0.25g was slowly injected intravenously. 30 minutes later, 5mL of blood was collected from the anterior vena cava and thoroughly mixed with 1U of thrombin. The mixture was then dispensed into five 2mL syringes (approximately half blood and half air) and allowed to stand at room temperature for about 40 minutes to form a thrombus. Subsequently, the pre-prepared thrombus was slowly injected through an existing intravenous access to establish a pulmonary embolism model, with continuous monitoring of respiratory status and overall response during the injection process.
[0055] Model beagle dogs were anesthetized and given intravenous injections. 18 F-TD-1 (55.5 MBq / vial) was administered via PET / CT whole-body imaging at 5, 15, 30, 60, and 90 minutes post-injection (PET single-bed scan time: 30 s; CT scan parameters: voltage 80 kV, current 100 mA). Figure 6 As shown, 18 F-TD-1 has good specificity for thrombi.
[0056] The above-described embodiments are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.
Claims
1. A radioactive nuclide molecular imaging agent, characterized in that: It is a compound with the structure shown in formula (I) or a pharmaceutically acceptable salt thereof. 。 2. A precursor compound for synthesizing the compound of claim 1, characterized in that: Its structure is shown in equation (II). 。 3. The method for preparing the radioactive nuclide molecular imaging agent according to claim 1, characterized in that: The precursor compound of formula (II) as described in claim 2 is combined with 18 F ions react in DMA solvent at 120°C under Cu(Py)4(OTf)2 catalysis to generate the compound of formula (I) as described in claim 1.
4. The method for preparing the radioactive nuclide molecular imaging agent according to claim 3, characterized in that: In dry K 18 The precursor compound of formula (II), Cu(Py)4(OTf)2, and DMA were added to the DMA solution of F, and the mixture was heated at 120°C for 20 minutes. After cooling, HI solution was added, and the protecting group was removed by heating. After cooling, NaOH solution was added for neutralization, and the product was separated by semi-preparative HPLC to obtain the target product.
5. The method for preparing the radioactive nuclide molecular imaging agent according to claim 3, characterized in that: The specific steps are as follows: (1) 4-(4-hydroxybutyl)piperidine-1-carboxylic acid tert-butyl ester, carbon tetrabromide, dichloromethane and triphenylphosphine were reacted at room temperature, and then the mixture was distilled under reduced pressure and subjected to rapid column chromatography to obtain compound 2; (2) Compound 2, sodium iodide, cesium carbonate and ((benzyloxy)carbonyl)-L-tyrosine tert-butyl ester were refluxed in acetonitrile, extracted with ethyl acetate, and then subjected to rapid column chromatography to obtain compound 3; (3) Compound 3 was reacted with hydrogen in methanol using Pd / C as a catalyst. After the reaction was complete, the mixture was filtered and evaporated to dryness to obtain compound 4; (4) Compound 4 reacted with 4-iodobenzenesulfonyl chloride in dichloromethane, was extracted and separated, and purified by rapid column chromatography to obtain compound 5; (5) Compound 5, hexamethyldistin and tetra(triphenylphosphine)palladium were heated in 1,4-dioxane, filtered and extracted, and then purified by rapid column chromatography.
6. A standard compound for comparison with the compound of claim 1, characterized in that: Its structure is shown in equation (Ⅲ). 。 7. The method for preparing the standard compound according to claim 6, characterized in that: The specific steps are as follows: 1) Compound 4 of claim 5 is reacted with 4-fluorobenzenesulfonyl chloride at room temperature, and then compound 7 is obtained by rapid column chromatography; 2) After reacting compound 7 obtained in step 1) with trifluoroacetic acid in dichloromethane, the mixture was distilled under reduced pressure and subjected to rapid column chromatography.
8. The application of the radionuclide molecular imaging agent of claim 1 in enhancing medical imaging during the diagnosis of thrombosis or atherosclerotic plaques.
9. The application according to claim 8, characterized in that: The diagnosis is achieved through positron emission tomography (PET) or PET / CT imaging.
10. The application of the radionuclide molecular imaging agent of claim 1 in molecular visualization imaging tools.