Application of high-specificity receptor molecular probe in preparation of brain tumor tracing drugs

Abstract

The invention belongs to the field of medicines, and particularly relates to application of a high-specificity receptor molecular probe in preparation of brain tumor tracing medicines. The PET / CT (positron emission tomography / computed tomography) result of small animals in the research shows that the tumor of the (R)-[18F] FBFP labeled nude mouse model is clearly visible, and high uptake and high tumor / brain ratio are shown. The results indicate that the (R)-[18F] FBFP has relatively high brain uptake and tumor uptake, good affinity and high specific binding in vivo, which indicates that the (R)-[18F] FBFP can clearly trace the brain tumor, and we infer that the (R)-[18F] FBFP and the (S)-[18F] FBFP can trace and distinguish different types and different levels of brain malignant tumors, and have very high clinical value and scientific research value.

Description

Technical Field

[0001] The invention belongs to the field of medicine, and in particular relates to an application of a highly specific receptor molecular probe in the preparation of a brain tumor tracing drug. Background Art

[0002] Brain tumor is a tumor that occurs in the brain, including glioblastoma, medulloblastoma and other malignant tumors. Its clinical prognosis is closely related to the tumor grade. Early and accurate grade has extremely important clinical and scientific research value for subsequent diagnosis and personalized treatment. At present, in clinical practice, brain tumors can be graded based on tissue and molecular pathology results after biopsy. However, biopsy of brain tumors occurring in high-risk areas (such as the brainstem) is usually difficult to perform. At the same time, the operation is obviously dependent on the doctor's skills, and the biopsy operation may also cause the tumor to worsen and spread. In addition, the existing FDG molecular probe tracer has significant limitations in the application of brain tumors. Therefore, it is particularly important to find a highly specific receptor molecular probe that is highly correlated with the malignancy grade of brain tumors and has good safety.

[0003] Therefore, based on this, the technical solution of the present invention is proposed. Summary of the invention

[0004] In order to solve the problems existing in the prior art, the present invention provides an application of a highly specific receptor molecular probe in the preparation of a brain tumor tracing drug, wherein the chemical structure of the highly specific receptor molecular probe is shown in Formula I:

[0005]

[0006] Preferably, the brain tumor tracer drug is a glioblastoma tracer drug;

[0007] And / or, the brain tumor tracer drug is a medulloblastoma tracer drug.

[0008] Preferably, the highly specific receptor molecular probe is a probe that has high specific binding to the σ1 receptor of intracranial in situ U87MG glioma;

[0009] And / or, the highly specific receptor molecular probe is a probe that has highly specific binding to the σ1 receptor of axillary ectopic U87MG glioma.

[0010] The present invention first proposes a method for preparing a standard probe, the flow chart is as follows Figure 1 As shown, the purpose is to facilitate comparison with subsequent high-specificity receptor molecule probes (labeled probes), and the preparation method of the standard probe is:

[0011] (i) Compound 1 (1.00 g, 9.79 mmol, Figure 1The compound marked as 1 in the reaction mixture) and solvent dichloromethane (15 mL) were added, followed by triethylamine (TEA, 2.83 ml, 19.58 mmol), 4-dimethylaminopyridine (DMAP, 0.24 g, 1.96 mmol), and p-toluenesulfonyl chloride (3.73 g, 19.58 mmol) was dissolved in DCM and added dropwise to the reaction solution at 0°C. After the reaction was completed, 100 mL of water was added to the reaction bottle and extracted with DCM (3×20 mL). The organic phase was washed with saturated brine, then combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was separated and purified by silica gel column chromatography (PE / EA=5 / 1) to obtain the target product 2 ( Figure 1 The compound marked as 2 in the above). Yield: 99%, yellow oily liquid, developing system: PE / EA=3 / 1 (R f =0.6).

[0012] (ii) Compound 3 (1.27 g, 6.52 mmol, Figure 1 The compound marked as 3 in the reaction mixture) and solvent CH3CN (20 mL) were added, followed by the addition of Cs2CO3 (3.19 g, 9.79 mmol), catalytic amounts of NaI (0.60 g, 3.26 mmol) and triethylamine (0.47 mL, 3.26 mmol), and finally the target product 2 (1.67 g, 6.52 mmol) and refluxed for 12 hours. After the reaction was completed, the mixture was cooled to room temperature and the reaction solvent ACN was removed under reduced pressure distillation. 10 mL of water was added to the reaction flask and extracted with DCM (3×10 mL). The organic phase was washed with saturated brine, and then the organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was separated and purified by silica gel column chromatography (DCM / MeOH=40 / 1) to obtain the target product 4 ( Figure 1 The compound marked as 4 in the above). Yield: 54%, light yellow solid, developed by DCM / MeOH=20 / 1 (R f =0.4).

[0013] Preferably, the method for preparing the highly specific receptor molecular probe comprises the following steps:

[0014] (1) Compound 5 is mixed with acetic anhydride, compound 6 and boric acid to react, and after the reaction is completed, the target product 7 is purified;

[0015] (2) Compound 9 is mixed with methanol, triethylamine and compound 8 are added to react, and after the reaction is completed, the target product 10 is purified;

[0016] (3) mixing the target product 10 and acetonitrile, then adding cesium carbonate, sodium iodide, triethylamine and the target product 2 to react, and purifying after the reaction is completed to obtain the target product 11;

[0017] (4) mixing the target product 11 with chloroform, then adding trifluoroacetic acid and oxone oxidant to react first, then adding the target product 7 to continue the reaction, and purifying after the reaction is completed to obtain the target product 12;

[0018] (5) Labeling the target product 12 to obtain the highly specific receptor molecule probe.

[0019] Preferably, in step (1), the reaction temperature is 30° C. and the reaction time is 0.5 h.

[0020] Preferably, in step (2), the reaction temperature is 60° C. and the reaction time is 3 h.

[0021] Preferably, in step (3), the reaction is carried out under reflux overnight.

[0022] Preferably, in step (4), the oxone oxidant is potassium persulfate complex salt, 2KHSO5·KHSO4·K2SO4.

[0023] Preferably, in step (4), the reaction is first carried out at room temperature for 1 hour; and then the reaction is continued at 30° C. for 0.5 hour.

[0024] In order to facilitate the understanding of the present invention, the related compounds mentioned in the present invention are described:

[0025] Compound 1: Tetrahydro-2-furanmethanol.

[0026] Target product 2: (tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonate;

[0027] (R)-(Tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonate;

[0028] (S)-(Tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonate.

[0029] Compound 3: 1-(4-fluorobenzyl)piperazine.

[0030] Target product 4:

[0031] Piperazine,1-[(4-fluorophenyl)methyl]-4-[[(2R)-tetrahydro-2-furanyl]methyl];

[0032] Piperazine,1-[(4-fluorophenyl)methyl]-4-[[(2S)-tetrahydro-2-furanyl]methyl].

[0033] Compound 5: Malonic acid.

[0034] Compound 6: Adipic ketone.

[0035] Target product 7: 6,10-Dioxaspiro[4.5]decane-7,9-dione.

[0036] Compound 8: 1-bromomethyl-4-iodobenzene, 1-(bromomethyl)-4-iodobenzene.

[0037] Compound 9: Piperazine anhydrous.

[0038] Target product 10: 1-(4-iodobenzyl)piperazine.

[0039] Target product 11:

[0040] Piperazine,1-[(4-iodophenyl)methyl]-4-[[(2R)-tetrahydro-2-furanyl]methyl];

[0041] Piperazine,1-[(4-iodophenyl)methyl]-4-[[(2S)-tetrahydro-2-furanyl]methyl].

[0042] Target product 12:

[0043] Iodonium,(7,9-dioxo-6,10-dioxaspiro[4.5]dec-8-yl)[4-[[4-[[(2R)-tetrahydro-2-furanyl]methyl]-1-piperazinyl]methyl]phenyl]-, inner salt;

[0044] Iodonium,(7,9-dioxo-6,10-dioxaspiro[4.5]dec-8-yl)[4-[[4-[[(2S)-tetrahydro-2-fu ranyl]methyl]-1-piperazinyl]methyl]phenyl]-, inner salt.

[0045] The beneficial effects of the present invention are:

[0046] The present invention uses a BALB / C nude mouse U87-MG orthotopic xenograft brain glioblastoma transplantation model, which can fully reflect the pathological grade of clinical glioblastoma, and performs radioligand (R)-[ 18 F]FBFP, (S)-[ 18 F]FBFP administration and (R)-[ 18 F]FBFP, (S)-[ 18 F]FBFP and blockers were co-administered and tested by small animal PET / CT equipment to explore the effect of (R)-[ 18 F]FBFP, (S)-[ 18 F]FBFP tracking of brain tumors. The results of small animal PET / CT in this study showed that: (R)-[ 18 The tumors in the nude mouse model labeled with F]FBFP were clearly visible, showing high uptake and high tumor / brain ratio. These results suggest that (R)-[ 18 F]FBFP has high brain uptake and high tumor uptake in vivo, good affinity and high specificity binding, indicating that (R)-[ 18 F]FBFP can clearly trace brain tumors, and we infer that (R)-[ 18 (F)-[18F]FBFP and (S)-[18F]FBFP can trace and distinguish different types and grades of brain malignancies, and have high clinical and scientific research value. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0048] Figure 1 yes[ 18 F] Synthesis process route of FBFP standard.

[0049] Figure 2 yes[ 18F] Synthesis route of FBFP labeling precursor.

[0050] Figure 3 Yes (R)-[ 18 F]FBFP and (S)-[ 18 F] Synthesis process route of FBFP.

[0051] Figure 4 Injection of radioligand (R)-[ 18 F] PET / CT images of orthotopic tumor-bearing U87MG nude mice 30 min after FBFP.

[0052] Figure 5 Injection of radioligand (R)-[ 18 F] PET / CT images of orthotopic tumor-bearing U87MG nude mice 90 min after FBFP.

[0053] Figure 6 Yes Yes Injection of radioligand (R)-[ 18 F] PET / CT images of axilla-bearing U87MG nude mice 30 min after FBFP.

[0054] Figure 7 Injection of radioligand (R)-[ 18 F] PET / CT images of axilla-bearing U87MG nude mice 90 min after FBFP. DETAILED DESCRIPTION

[0055] To make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be described in detail below. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other implementation methods obtained by ordinary technicians in this field without creative work belong to the scope of protection of the present invention.

[0056] Example

[0057] This embodiment provides a method for preparing a highly specific receptor molecular probe, which includes the following steps. The process flow chart is shown in FIG. Figure 2 , Figure 3 As shown:

[0058] (1) Compound 5 (10.5 g, 100 mmol, Figure 2 The compound marked as 5 in the above solution was added, and then Ac2O (12.3 g, 120 mmol), compound 6 (8.4 g, 100 mmol, Figure 2The compound marked as 6 in the reaction mixture) and catalyst boric acid (19 mg, 0.3 mmol). The reaction solution was reacted at 30°C for 0.5 h. After the reaction was completed, 20 mL of water was added to the reaction flask and extracted with DCM (3×10 mL). The organic phase was washed with saturated brine, then combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was recrystallized from ether to obtain the target product 7 ( Figure 2 The compound marked as 7 in the above was prepared with a yield of 28%.

[0059] (2) Compound 9 (1.72 g, 20 mmol, Figure 2 The compound marked as 9 in the mixture) and solvent MeOH (20 mL) were added, followed by TEA (2.2 mL, 15 mmol), and then compound 8 (2.97 g, 10 mmol, Figure 2 The compound marked as 8 in the reaction mixture was dissolved in MeOH (20 mL) and added dropwise to the reaction solution at room temperature. After the addition was completed, the reaction solution was reacted at 60°C for 3 h. After the reaction was completed, the mixture was cooled to room temperature and the reaction solvent MeOH was removed under reduced pressure distillation. 20 mL of water was added to the reaction flask and extracted with DCM (4×10 mL). The organic phase was washed with saturated brine, and then the organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (DCM / MeOH / TEA=10 / 1 / 0.5) to obtain the target product 10 ( Figure 2 The compound marked as 10 in the above). Yield: 94%, white solid, developing system: DCM / MeOH / TEA=20 / 1 / 0.5 (R f =0.5).

[0060] (3) Compound 10 (2.33 g, 7.72 mmol) and solvent ACN (20 mL) were added to a 100 mL round-bottom flask, followed by Cs2CO3 (7.55 g, 23.16 mmol), catalytic amount of NaI (0.58 g, 3.86 mmol) and triethylamine (0.39 mL, 3.86 mmol), and finally the target product 2 (2.47 g, 9.65 mmol) and refluxed overnight. After the reaction was completed, the mixture was cooled to room temperature and the reaction solvent ACN was removed under reduced pressure. 10 mL of water was added to the reaction flask and extracted with DCM (3×10 mL). The organic phase was washed with saturated brine, then the organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was separated and purified by silica gel column chromatography (DCM / MeOH=40 / 1) to obtain the target product 11 ( Figure 2 The compound marked as 11 in the above). Yield: 58%, light yellow solid, developed by DCM / MeOH=20 / 1 (R f =0.4).

[0061] (4) Compound 11 (0.60 g, 1.55 mmol) and solvent CHCl3 (5 mL) were added to a 25 mL round-bottom flask, followed by trifluoroacetic acid TFA (2.36 mL, 31.07 mmol) and oxone oxidant (0.95 g, 3.11 mmol). The mixed solution was reacted at room temperature for 1 h, and then the reaction solvent and TFA were removed under reduced pressure distillation. EtOH (5 mL) was added, and the pH was adjusted to greater than 10 with Na2CO3 (10% aqueous solution) and Na2CO3 saturated solution, respectively. It was noted that the amount of ethanol and aqueous solution was kept equal during the process. Then the target product 7 (0.53 g, 3.11 mmol) was added, and the solution was reacted at 30°C for 0.5 h. After the reaction was completed, 10 mL of water was added to the reaction flask, and extracted with ethyl acetate (4×10 mL). The organic phase was washed with saturated brine, and then the organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was separated and purified by silica gel column chromatography (EtOH / EA=2 / 1) to obtain the target product 12 ( Figure 2 The compound marked as 12 in the above). Yield: 25%, white solid, developed by EtOH / EA=1 / 1 (R f =0.4).

[0062] (5) 18F-labeled σ1 receptor compound (S)-[ 18 F]FBFP and (R)-[ 18 Preparation of [F]FBFP:

[0063] (5-1) A QMA column was activated with 10 mL of NaHCO3 (10%), 10 mL of H2O, and 10 mL of ethanol, respectively, to capture fluoride ions. A C-18 column was activated with 10 mL of ethanol and H2O for solid phase extraction.

[0064] (5-2) Prepare 1 mL K 2.2.2 / K2CO3 eluent will [ 18 F]F - Elute from the QMA column into a reaction flask, heat at 110°C under N2 to remove water, and then dry with anhydrous acetonitrile three times.

[0065] (5-3) After the water removal is completed, the reaction bottle is sealed, 2-3 mg of the labeled precursor (target product 12) is dissolved in 0.5 mL of anhydrous ACN, and transferred to a container containing [ 18 F]F - / K 2.2.2 The complex is fully mixed in a reaction bottle and heated at 120° C. for 10 min to obtain the product.

[0066] Among them, the 18 F]F - / K 2.2.2 The complex contains 13 mg of 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane (K 2.2.2 ), 1.5 mg triphenylphosphine and 1.1 mg potassium carbonate + [ 18 F]F - Mixture, radioactivity 10~1000mCi.

[0067] (5-4) After the reaction is completed, the mixture is cooled to room temperature, the radioactivity is measured, and the product is separated and purified by HPLC. The HPLC conditions are as follows: the mobile phase of the HPLC semi-preparative column (ReproSil-PurBasic-C18 column, 250×10 mm, 5 μm) is preferably 50% acetonitrile aqueous solution containing 0.1% triethylamine, and the flow rate is 4 mL / min.

[0068] (5-5) Identification of products after separation and purification: In this scheme, the obtained reaction product is identified by HPLC. Preferably, the HPLC conditions are as follows: an analytical column (Agela Venusil MP C18 column, 250×4.6 mm, 5 μm), and the HPLC analysis mobile phase is preferably a 50% acetonitrile aqueous solution containing 0.1% triethylamine, and the flow rate is 1 mL / min. Through HPLC separation and purification, it is identified that the radiochemical purity is greater than 99%, and the radiochemical yield is 19% to 27%.

[0069] Verification Example

[0070] The U87-MG nude mouse brain glioma orthotopic xenograft model was injected with synthetic radioligand (R)-[ 18 F]FBFP was used for PET / CT imaging and blocking studies were performed by co-administering the selective σ1 receptor ligand blocker SA4503 (5 μmol / kg).

[0071] (1) Establishment of U87-MG nude mouse brain glioma orthotopic and axillary xenograft models

[0072] Establishment of in situ model: U87 cells in logarithmic phase were collected and prepared into a concentration of 5×10 5 / 5μL of cell suspension. The nude mouse was placed in an anesthesia box, and the isoflurane gas flow rate was adjusted to 2.0L / min and the content was 2%. After 5 minutes of anesthesia, the nude mouse was taken out and placed prone on a stereotaxic instrument, the upper teeth were fixed on the anesthesia mask, and the isoflurane concentration was adjusted to 1.5%. The two ear bars were placed in the external auditory canal of the nude mouse to fix the head of the nude mouse to keep it horizontal. Erythromycin eye ointment was applied to both eyes of the nude mouse, iodine was used to disinfect the skin of the head, and surgical scissors were used to cut about 2cm from the middle of the line between the two eyes to the back to expose the skull, level it, drill a hole in the right caudate nucleus, draw and inject 5μL of cell suspension, leave the needle for 10 minutes after the injection, slowly withdraw the needle, seal the drill hole with bone wax, suture the surgical incision, and apply an appropriate amount of penicillin.

[0073] Establishment of the axillary model: U87 cells in logarithmic phase growth were collected and prepared at a concentration of 1×10 5 / μL of cell suspension, use a syringe to draw 200μL of cell suspension and inject it under the skin of the right armpit of nude mice.

[0074] (2) Small animal PET / CT detection method

[0075] Mice (15.0-20.0 g) were injected with 0.1 mL of (R)-[ 18 F]FBFP injection (8.14-14.80MBq), 30 minutes after injection, the mice were placed in a pre-anesthesia box and anesthetized with isoflurane (airflow rate 2.0L / min, containing 3.0% isoflurane). Then they were immediately transferred to the scanning bed, the airflow was adjusted to 0.8-1.0L / min (containing 1.5-2.0% isoflurane), and micoPET / CT static imaging (Inveon PET / CT, Siemens, Germany) was performed. The PET scanning time was 10 minutes. The CT scanning was 2 beds, the mode was "magnification low", and the specific parameters were as follows: projection: 180; binning: 4×4; transaxial field of view: 53.9mm; axial scanning length: 134mm; voltage: 80kV; current: 500μA.

[0076] (3) Image processing

[0077] Image processing was performed using the post-processing workstation Inveon Research Workplace that comes with microPET / CT. PET reconstruction used the OSEM3D / SP-MAP algorithm with the following parameters: OESM3D: 2 iterations; MAP: 10 iterations; Target resolution: 1.8 mm; Matrix size: 256 × 256; Image zoom: 1. CT reconstruction used the Feldkamp algorithm. Reconstructed data were performed using PMOD software (PMOD Technologies, Switzerland). CT scans were used as the basis for positioning, and the entire mouse brain was drawn using CT. The region of interest (ROI) was drawn and the PET images were integrated to calculate the brain and tumor SUV values.

[0078] Study Results

[0079] The research data are shown in Tables 1 to 4 and Figures 4 to 7 As shown, specifically:

[0080] (R)-[ 18 F]FBFP small animal PET / CT imaging shows (R)-[ 18 F]FBFP showed clear tumor imaging in nude mice with orthotopically implanted U87MG glioma, as well as high tumor uptake and high tumor / brain contrast. The tumor SUVmax at 30min and 90min were 1.91±0.27 and 1.74±0.26, respectively (n=3). Simultaneous injection of SA4503 (5μmol / kg) significantly reduced the tumor uptake rate by 57% and 54% at 30min and 90min, respectively, indicating that (R)-[ 18 F]FBFP has a high specificity for the σ1 receptor of intracranial orthotopic U87MG glioma.

[0081] (R)-[ 18 F]FBFP small animal PET / CT imaging shows (R)-[ 18 F]FBFP showed clear tumor imaging in nude mouse axillary xenograft U87MG gliomas, as well as high tumor uptake, high tumor-brain contrast and high tumor-muscle contrast. The tumor SUVmax at 30 min and 90 min was 1.92 ± 0.16 and 1.49 ± 0.08, respectively (n = 3). Simultaneous injection of SA4503 (5 μmol / kg) significantly reduced the tumor uptake rate by 59% and 60% at 30 min and 90 min, respectively, indicating that (R)-[ 18 F]FBFP has high specificity for the σ1 receptor of axillary ectopic U87MG glioma.

[0082] Radioligand (R)-[ 18 F]FBFP has good affinity and high subtype selectivity for σ1 receptor in intracranial homologous glioma transplantation, high tumor uptake and high specific binding to σ1 receptor. Based on this, we infer that (R)-[ 18 F]FBFP and (S)-[ 18 F]FBFP can also distinguish different types of brain tumors and different grades of malignant brain tumors, which has high clinical and scientific research value.

[0083] In summary, this invention: radioligand (R)-[ 18 F]FBFP and (S)-[ 18 F]FBFP has great clinical value as a suitable σ1 receptor probe in brain tumor imaging.

[0084] Table 1 Injection of radioligand (R)-[ 18 F] PET / CT imaging results of orthotopic tumor-bearing U87MG nude mice 30 min after FBFP

[0085]

[0086] Table 2 Injection of radioligand (R)-[ 18 F] PET / CT imaging results of orthotopic tumor-bearing U87MG nude mice 90 minutes after FBFP

[0087]

[0088]

[0089] Table 3 Injection of radioligand (R)-[ 18 F] PET / CT imaging results of axillary tumor-bearing U87MG nude mice 30 minutes after FBFP

[0090]

[0091] Table 4 Injection of radioligand (R)-[ 18 F] PET / CT imaging results of axillary tumor-bearing U87MG nude mice 90 minutes after FBFP

[0092]

[0093]

[0094] The above is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art can easily think of changes or substitutions within the technical scope disclosed by the present invention, which should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. An application of a highly specific receptor molecular probe in the preparation of a brain tumor tracing drug, characterized in that: The chemical structural formula of the highly specific receptor molecule probe is shown in Formula I:

2. The use of a highly specific receptor molecular probe in the preparation of a brain tumor tracing drug according to claim 1, characterized in that: The brain tumor tracing drug is a glioblastoma tracing drug; And / or, the brain tumor tracer drug is a medulloblastoma tracer drug.

3. The use of a highly specific receptor molecular probe in the preparation of a brain tumor tracing drug according to claim 1, characterized in that: The highly specific receptor molecular probe is a probe that has high specific binding to the σ1 receptor of intracranial in situ U87MG glioma; And / or, the highly specific receptor molecular probe is a probe that has highly specific binding to the σ1 receptor of axillary ectopic U87MG glioma.

4. The use of a highly specific receptor molecular probe in the preparation of a brain tumor tracing drug according to claim 1, characterized in that: The method for preparing the highly specific receptor molecule probe comprises the following steps: (1) Compound 5 is mixed with acetic anhydride, compound 6 and boric acid to react, and after the reaction is completed, the target product 7 is purified; (2) Compound 9 is mixed with methanol, triethylamine and compound 8 are added to react, and after the reaction is completed, the target product 10 is purified; (3) mixing the target product 10 and acetonitrile, then adding cesium carbonate, sodium iodide, triethylamine and the target product 2 to react, and purifying after the reaction is completed to obtain the target product 11; (4) mixing the target product 11 with chloroform, then adding trifluoroacetic acid and oxone oxidant to react first, then adding the target product 7 to continue the reaction, and purifying after the reaction is completed to obtain the target product 12; (5) Labeling the target product 12 to obtain the highly specific receptor molecule probe.

5. The use of a highly specific receptor molecular probe in the preparation of a brain tumor tracing drug according to claim 4, characterized in that: In step (1), the reaction temperature is 30° C. and the reaction time is 0.5 h.

6. The use of a highly specific receptor molecular probe in the preparation of a brain tumor tracing drug according to claim 4, characterized in that: In step (2), the reaction temperature is 60° C. and the reaction time is 3 h.

7. The use of a highly specific receptor molecular probe in the preparation of a brain tumor tracing drug according to claim 4, characterized in that: In step (3), the reaction is carried out under reflux overnight.

8. The use of a highly specific receptor molecular probe in the preparation of a brain tumor tracing drug according to claim 4, characterized in that: In step (4), the oxone oxidant is potassium persulfate complex salt, 2KHSO5·KHSO4·K2SO4.

9. The use of a highly specific receptor molecular probe in the preparation of a brain tumor tracing drug according to claim 4, characterized in that: In step (4), the reaction is first carried out at room temperature for 1 h; and then the reaction is continued at 30° C. for 0.5 h.

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