A preparation method of an 18F-labeled boron phenylalanine PET tracer targeting LAT1

Abstract

This invention discloses a method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer, specifically relating to the field of radiopharmaceutical chemistry. The method includes the following steps: first, methyl 2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate is converted to a trifluoromethanesulfonate intermediate, followed by a boronization reaction to introduce a borate ester protecting group; subsequently, through the preparation of an aromatic ononium salt precursor, high-efficiency fluorine labeling is achieved using crown ether-promoted 18F nucleophilic aromatic substitution; finally, hydrolysis and deprotection are performed under acidic conditions, followed by pH adjustment, C18 chromatography purification, QMA column desalting, and sterile filtration to obtain a high-purity, high-stability 18F-FBPA injection solution. This invention overcomes the problems of easy side reactions and low labeling efficiency of the borate group in traditional methods, achieving the preparation of a tracer with radiochemical purity >96%, radiochemical yield of approximately 20%, and specific activity >50 GBq / μmol.

Description

Technical Field

[0001] This invention relates to the field of radiopharmaceutical chemistry, and specifically to a method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer. Background Technology

[0002] 18 Due to its near-ideal physical properties, fluorocarbons (F) have become the most commonly used radionuclide in positron emission tomography (PET), playing an irreplaceable role in tumor diagnosis, treatment efficacy evaluation, and new drug development. However, [the text abruptly ends here, likely due to an incomplete sentence or missing information]. 18 The efficient and specific introduction of F into bioactive molecules with complex structures, especially into targeted small molecules with multiple sensitive functional groups, has always been a core challenge in the field of radiochemical synthesis.

[0003] This labeling difficulty stems primarily from several interrelated technical bottlenecks: First, 18 The fluoride ion itself has limited nucleophilic reactivity, making it difficult to react efficiently with unactivated aromatic rings or alkyl sites in many chemical environments. Secondly, target molecules with diagnostic or therapeutic potential often have fragile structures, easily decomposing, racing, or undergoing side reactions under strong alkaline, high-temperature, or redox conditions, severely limiting the window of conditions for labeling reactions. Furthermore, 18 The short half-life of F requires that the labeling and purification process be completed efficiently in a short time, which further reduces the feasibility of using multi-step protection-deprotection strategies or complex purification methods.

[0004] The aforementioned challenges are particularly prominent in the development of boron-containing amino acid-based PET tracers targeting the LAT1 transporter. These molecules are not only potential PET imaging agents but also key drugs for boron neutron capture therapy of BNCT. However, the boronic acid groups in their molecular structure are chemically reactive, posing challenges in conventional... 18 Under F-labeled conditions, side reactions such as hydrolysis, dimerization, or deboronization readily occur, resulting in extremely low yields and mixed products in traditional direct nucleophilic fluorination routes. Therefore, there is an urgent need to develop a novel, mild, and efficient method. 18 The F-labeling strategy is compatible with sensitive functional groups such as boric acid, enabling the achievement of high radiochemical purity and high specific activity. 18 The reliable preparation of F-labeled borophenylalanine will promote its application in the integrated precision diagnosis and treatment of tumors. Summary of the Invention

[0005] To overcome the aforementioned deficiencies of the prior art, embodiments of the present invention provide a method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer, thus solving the problem of PET tracer... 18 The problem of F-marking difficulties.

[0006] To achieve the above objectives, the present invention provides the following technical solution: A method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer specifically includes the following steps: S1: A mixture of methyl 2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate, N,N-bis(trifluoromethylsulfonyl)aniline, and triethylamine was dissolved in dichloromethane. The mixture was then stirred and reacted at 0°C, and the reaction was allowed to return to room temperature. The solvent was then rotary evaporated to obtain methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate. (Reference reaction equation follows.) Figure 2 ; S2: Methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride, pinacol diboronate, and potassium acetate prepared in S1 are dissolved in a 1,4-dioxane solvent. The system is then heated to react, and the solvent is rotary evaporated to obtain methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate. The reaction equation is referenced. Figure 3 ; S3: Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate, dibenzo[b,d]thiophene 5-oxide, and trifluoromethanesulfonic anhydride prepared in S2 were dissolved in dichloromethane and reacted at sub-zero temperature for 30 minutes, followed by reaction at room temperature for 30 minutes. The solvent was then rotary evaporated to obtain 5-(2-(2-amino-3-methoxy-3-oxopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonic acid onium. The reaction equation is referenced. Figure 4 ; S4: The 5-(2-(2-amino-3-methoxy-3-oxopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborane-2-yl)phenyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate, 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane, and potassium fluoride (fluorine- 18 F) was dissolved in acetonitrile, and the system was then heated to react. The solvent was then rotary evaporated to give 2-amino-3-(2-(fluoro-) 18 Methyl f(F)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate, reaction equation referenced. Figure 5 ; S5: The 2-amino-3-(2-(fluoro-) obtained last in S4 18 Methyl F)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate was dissolved in 12M hydrochloric acid, and then heated to react and give 2-amino-3-(2-(fluoro- 18 F)-4-Borate-phenyl)propionic acid, reaction equation referenced. Figure 6 ; S6: After the final product of S5 has cooled to room temperature, slowly add 7M sodium hydroxide solution and stir thoroughly for 10 minutes; S7: After the product reaction in S6 is complete, add deionized water at a ratio of 1:3 and mix thoroughly. Then place this mixture on a C18 column for isocratic elution and finally collect the liquid. S8: The final solution collected in S7 is desalted and concentrated using a QMA anion exchange column. The column is then rinsed with physiological saline to collect the liquid. The concentrated solution and the rinsing liquid are filtered through a sterile membrane to obtain... 18 F-FBPA injection solution should be stored at low temperature.

[0007] Preferably, in S1, methyl 2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate, N,N-bis(trifluoromethylsulfonyl)aniline, and triethylamine are dissolved in dichloromethane and then stirred at 200 rpm for 1.5 h at 0 °C, and then the mixture is restored to room temperature of 25 °C and stirred at 200 rpm for 1 h.

[0008] Preferably, in step S2, the final product prepared in step S1, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride, pinacol diborate, and potassium acetate are dissolved in a 1,4-dioxane solvent, and then heated to 120°C and stirred at 200 rpm for 2 hours.

[0009] Preferably, in step S3, the product finally prepared in step S2, dibenzo[b,d]thiophene 5-oxide, and trifluoromethanesulfonic anhydride are dissolved in dichloromethane and then stirred continuously at 200 rpm for 30 minutes at a temperature of -40°C, and then stirred at 200 rpm for 30 minutes at room temperature of 25°C.

[0010] Preferably, in S4, the product finally obtained in S3, 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane, and potassium fluoride (fluorine- 18 F) was dissolved in acetonitrile, and then placed at 110°C and stirred continuously at 200 rpm for 20 minutes.

[0011] Preferably, in step S5, the product obtained in step S4 is dissolved in a 12M hydrochloric acid solution, and then the system is heated to 110°C and stirred continuously for 10 minutes.

[0012] Preferably, in step S6, a 7M sodium hydroxide solution is slowly added dropwise to the cooled product obtained in step S5 until the pH of the system is 4.0 to 4.5.

[0013] Preferably, in step S7, deionized water is added to the final product obtained in step S6 at a ratio of 1:3, and the product is then subjected to moderate elution on a C18 column with a mobile phase of 0.1% acetic acid / 1~10% acetonitrile and a flow rate of 1 mL / min.

[0014] Preferably, in step S8, the collected liquid is filtered through a 0.22 μm sterile filter membrane. 18 F-FBPA injection.

[0015] Preferably, in S8 18 F-FBPA should be stored in a low-temperature, oxygen-free environment at -20 to -10°C.

[0016] The technical effects and advantages of the method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer of the present invention are as follows: 1. In this invention, the phenolic hydroxyl group in methyl 2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate used in S1 is converted into trifluoromethanesulfonate ester. This process is carried out at 0°C. N,N-bis(trifluoromethanesulfonyl)aniline is used to react with triethylamine to generate methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate ester. The trifluoromethanesulfonate ester is a leaving group, which is beneficial for the subsequent borylation reaction. The low-temperature reaction conditions can avoid substrate decomposition and side reactions.

[0017] 2. In this invention, in the presence of palladium catalyst in S2, trifluoromethanesulfonate and pinacol diboronic acid undergo a boronization reaction to generate a borate-protected precursor. The introduction of borate groups provides reaction sites for subsequent 18F labeling, and the stable form of borate ester avoids polymerization and hydrolysis of free boric acid in subsequent steps.

[0018] 3. In this invention, the dibenzo[b,d]thiophene 5-oxide used in S3 reacts with trifluoromethanesulfonic anhydride at low temperature to generate a highly electron-deficient aromatic onium salt structure. The aromatic onium salt significantly enhances the nucleophilic substitution reactivity of the aromatic ring for fluoride ions. The low-temperature reaction avoids side reactions, thereby protecting the borate ester and carbamate ester.

[0019] 4. In this invention, under the action of crown ether analogues in S4 18 Potassium fluoride (F-fluoride) undergoes a nucleophilic aromatic substitution reaction with aromatic ononium salts, resulting in... 18The introduction of F into the benzene ring, where the crown ether complexes with potassium ions, enhances the nucleophilicity and reaction efficiency of fluoride ions, and avoids radioactive loss or side reactions caused by high-temperature and long-term reactions under mild conditions.

[0020] 5. In this invention, hydrochloric acid is added to S5 and heated to achieve ester hydrolysis and deprotection of borate ester, thereby generating free borophenylalanine.

[0021] 6. In this invention, sodium hydroxide is added to S6 to neutralize the pH of the system to 4.0-4.5, so that the product is in a slightly acidic environment, thereby avoiding alkaline conditions. 18 F shedding and the side reaction with boric acid.

[0022] 7. In this invention, the C18 reversed-phase chromatographic column used in S7 enhances selectivity through a low proportion of acetonitrile, thereby effectively removing unreacted precursors and byproducts, while acetic acid is used as an additive to improve peak shape and separation efficiency.

[0023] 8. In this invention, the QMA anion exchange column used in S8 is used to remove inorganic salts, while physiological saline is used to wash and collect the product, which is finally obtained by passing it through a sterile filter membrane. 18 F-FBPA. Attached Figure Description

[0024] Figure 1 This is a schematic diagram of a LAT1-targeted 18F-labeled boron phenylalanine PET tracer proposed in this invention; Figure 2 This is the S1 step reaction equation for a LAT1-targeted 18F-labeled boron phenylalanine PET tracer proposed in this invention; Figure 3 This is the S2 step reaction equation for a LAT1-targeted 18F-labeled boron phenylalanine PET tracer proposed in this invention; Figure 4 This is the S3 step reaction equation for a LAT1-targeted 18F-labeled boron phenylalanine PET tracer proposed in this invention; Figure 5 This is the S4 step reaction equation for a LAT1-targeted 18F-labeled boron phenylalanine PET tracer proposed in this invention; Figure 6 This is the S5 step reaction equation for a LAT1-targeted 18F-labeled boron phenylalanine PET tracer proposed in this invention. Detailed Implementation

[0025] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0026] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0027] Example 1 This embodiment provides a method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer, the specific implementation steps of which include: Experimental materials: Methyl 2-(tert-Butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate, N,N-bis(trifluoromethanesulfonyl)aniline, triethylamine, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride, pinacol diboronate, potassium acetate, trifluoromethanesulfonic anhydride, 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane and potassium fluoride (fluorine- 18 F), FBPA eluent, 1 mL acetonitrile for column loading, precursor, copper tetrapyridine trifluoromethanesulfonate, DMF, pyridine, 12M hydrochloric acid, 7M sodium hydroxide, ascorbic acid, deionized water, mobile phase acetate-sodium acetate buffer.

[0028] Experimental objective: Preparation of LAT1-targeted 18 F-labeled boron phenylalanine PET tracer.

[0029] Experimental steps: S1: A mixture of methyl 2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate, N,N-bis(trifluoromethylsulfonyl)aniline, and triethylamine was dissolved in dichloromethane. The mixture was then stirred and reacted at 0°C for 1.5 h, and then the mixture was brought back to room temperature and reacted at 25°C for 1 h. The solvent was then rotary evaporated to obtain methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate. S2: Methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride, pinacol diboronate, and potassium acetate prepared in S1 were dissolved in 1,4-dioxane solvent. The system was then heated to 120°C and reacted for 12 hours. The solvent was then rotary evaporated to obtain methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate. S3: Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate, dibenzo[b,d]thiophene 5-oxide, and trifluoromethanesulfonic anhydride prepared in S2 were dissolved in dichloromethane and reacted at -40°C for 30 minutes, followed by reaction at room temperature of 25°C for 30 minutes. The solvent was then rotary evaporated to obtain 5-(2-(2-amino-3-methoxy-3-oxopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonic acid onium; S4: The 5-(2-(2-amino-3-methoxy-3-oxopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborane-2-yl)phenyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate, 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane, and potassium fluoride (fluorine- 18 F) was dissolved in acetonitrile, and the system was then heated to 110°C and reacted for 20 minutes. The solvent was then rotary evaporated to obtain 2-amino-3-(2-(fluoro-) 18 Methyl F)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate; S5: The 2-amino-3-(2-(fluoro-) obtained last in S4 18 Methyl F)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate was dissolved in 12M hydrochloric acid, and then heated to 110°C for 10 minutes to give 2-amino-3-(2-(fluoro-18 F)-4-Borate-phenyl)propionic acid; S6: After the final product of S5 has cooled to room temperature, slowly add 7M sodium hydroxide solution and adjust the pH of the system to 4.0 and stir thoroughly for 10 minutes; S7: After the product reaction in S6 is complete, add deionized water at a ratio of 1:3 and mix thoroughly. Then, place this mixture on a C18 column with a mobile phase of 0.1% acetic acid / 1% acetonitrile and a flow rate of 1 mL / min for isocratic elution and finally collect the liquid. S8: The final solution collected in S7 is desalted and concentrated using a QMA anion exchange column. The column is then rinsed with physiological saline to collect the liquid. The concentrated solution and the liquid obtained from the saline rinse are filtered through a 0.22 μm sterile filter membrane to obtain... 18 F-FBPA injection.

[0030] Experimental results: See Table 1 for details.

[0031] Table 1: Test Results of Example 1

[0032] This embodiment achieves neutralization at a pH of 4.0 through precise control. 18 F-FBPA maintains fluorine labeling stability in a slightly acidic environment, avoiding defluorination side reactions; a C18 column with a low proportion of acetonitrile (1%) is used to achieve high-selectivity separation, effectively removing hydrophilic and hydrophobic impurities; finally, desalting is performed using a QMA anion exchange column, significantly reducing inorganic ion residues, thereby achieving an optimal balance in reaction mechanism, purification efficiency, and formulation stability, resulting in high radiochemical purity and radiochemical yield.

[0033] Example 2 This embodiment provides a method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer, the specific implementation steps of which include: Experimental materials: Methyl 2-(tert-Butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate, N,N-bis(trifluoromethanesulfonyl)aniline, triethylamine, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride, pinacol diboronate, potassium acetate, trifluoromethanesulfonic anhydride, 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane and potassium fluoride (fluorine- 18 F), FBPA eluent, 1 mL acetonitrile for column loading, precursor, copper tetrapyridine trifluoromethanesulfonate, DMF, pyridine, 12M hydrochloric acid, 7M sodium hydroxide, ascorbic acid, deionized water, mobile phase acetate-sodium acetate buffer.

[0034] Experimental objective: Preparation of LAT1-targeted 18 The effect of F-labeled boron phenylalanine PET tracer on the separation efficiency was investigated by changing the HPLC purification conditions.

[0035] Experimental steps: S1: A mixture of methyl 2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate, N,N-bis(trifluoromethylsulfonyl)aniline, and triethylamine was dissolved in dichloromethane. The mixture was then stirred and reacted at 0°C for 1.5 h, and then the mixture was brought back to room temperature and reacted at 25°C for 1 h. The solvent was then rotary evaporated to obtain methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate. S2: Methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride, pinacol diboronate, and potassium acetate prepared in S1 were dissolved in 1,4-dioxane solvent. The system was then heated to 120°C and reacted for 12 hours. The solvent was then rotary evaporated to obtain methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate. S3: Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate, dibenzo[b,d]thiophene 5-oxide, and trifluoromethanesulfonic anhydride prepared in S2 were dissolved in dichloromethane and reacted at -40°C for 30 minutes, followed by reaction at room temperature of 25°C for 30 minutes. The solvent was then rotary evaporated to obtain 5-(2-(2-amino-3-methoxy-3-oxopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonic acid onium; S4: The 5-(2-(2-amino-3-methoxy-3-oxopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborane-2-yl)phenyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate, 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane, and potassium fluoride (fluorine- 18 F) was dissolved in acetonitrile, and the system was then heated to 110°C and reacted for 20 minutes. The solvent was then rotary evaporated to obtain 2-amino-3-(2-(fluoro-) 18 Methyl F)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate; S5: The 2-amino-3-(2-(fluoro-) obtained last in S4 18 Methyl F)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate was dissolved in 12M hydrochloric acid, and then heated to 110°C for 10 minutes to give 2-amino-3-(2-(fluoro- 18 F)-4-Borate-phenyl)propionic acid; S6: After the final product of S5 has cooled to room temperature, slowly add 7M sodium hydroxide solution and adjust the pH of the system to 4.0 and stir thoroughly for 10 minutes; S7: After the product reaction in S6 is complete, add deionized water at a ratio of 1:3 and mix thoroughly. Then, place this mixture on a C18 column with a mobile phase of 0.1% acetic acid / 5% acetonitrile and a flow rate of 2 mL / min for isocratic elution and finally collect the liquid. S8: The final solution collected in S7 is desalted and concentrated using a QMA anion exchange column. The column is then rinsed with physiological saline to collect the liquid. The concentrated solution and the liquid obtained from the saline rinse are filtered through a 0.22 μm sterile filter membrane to obtain... 18 F-FBPA injection.

[0036] Experimental results: See Table 2 for details.

[0037] Table 2: Test Results of Example 2

[0038] Although this embodiment maintains the same neutralization and desalting steps as in Example 1, the proportion of acetonitrile in the HPLC mobile phase is increased to 5% and the flow rate is increased to 2 mL / min, resulting in enhanced elution intensity and a decrease in the theoretical plate number of the chromatographic column. This causes ^18^F-FBPA to co-elute with structurally similar impurities, reducing the separation resolution and thus causing a significant decrease in radiochemical purity and radiochemical yield.

[0039] Example 3 This embodiment provides a method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer, the specific implementation steps of which include: Experimental materials: Methyl 2-(tert-Butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate, N,N-bis(trifluoromethanesulfonyl)aniline, triethylamine, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride, pinacol diboronate, potassium acetate, trifluoromethanesulfonic anhydride, 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane and potassium fluoride (fluorine- 18F), FBPA eluent, 1 mL acetonitrile for column loading, precursor, copper tetrapyridine trifluoromethanesulfonate, DMF, pyridine, 12M hydrochloric acid, 7M sodium hydroxide, ascorbic acid, deionized water, mobile phase acetate-sodium acetate buffer.

[0040] Experimental objective: Preparation of LAT1-targeted 18 F-labeled boron phenylalanine PET tracer was used to investigate its effect on product purity and stability by omitting the desalting step. Experimental steps: S1: A mixture of methyl 2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate, N,N-bis(trifluoromethylsulfonyl)aniline, and triethylamine was dissolved in dichloromethane. The mixture was then stirred and reacted at 0°C for 1.5 h, and then the mixture was brought back to room temperature and reacted at 25°C for 1 h. The solvent was then rotary evaporated to obtain methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate. S2: Methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride, pinacol diboronate, and potassium acetate prepared in S1 were dissolved in 1,4-dioxane solvent. The system was then heated to 120°C and reacted for 12 hours. The solvent was then rotary evaporated to obtain methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate. S3: Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate, dibenzo[b,d]thiophene 5-oxide, and trifluoromethanesulfonic anhydride prepared in S2 were dissolved in dichloromethane and reacted at -40°C for 30 minutes, followed by reaction at room temperature of 25°C for 30 minutes. The solvent was then rotary evaporated to obtain 5-(2-(2-amino-3-methoxy-3-oxopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonic acid onium; S4: The 5-(2-(2-amino-3-methoxy-3-oxopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborane-2-yl)phenyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate, 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane, and potassium fluoride (fluorine- 18F) was dissolved in acetonitrile, and the system was then heated to 110°C and reacted for 20 minutes. The solvent was then rotary evaporated to obtain 2-amino-3-(2-(fluoro-) 18 Methyl F)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate; S5: The 2-amino-3-(2-(fluoro-) obtained last in S4 18 Methyl F)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate was dissolved in 12M hydrochloric acid, and then heated to 110°C for 10 minutes to give 2-amino-3-(2-(fluoro- 18 F)-4-Borate-phenyl)propionic acid; S6: After the final product of S5 has cooled to room temperature, slowly add 7M sodium hydroxide solution and adjust the pH of the system to 4.0 and stir thoroughly for 10 minutes; S7: After the product reaction in S6 is complete, add deionized water at a ratio of 1:3 and mix thoroughly. Then, place this mixture on a C18 column with a mobile phase of 0.1% acetic acid / 1% acetonitrile and a flow rate of 1 mL / min for isocratic elution and finally collect the liquid. S8: Filter the final solution collected in S7 through a 0.22μm sterile filter membrane to obtain... 18 F-FBPA injection.

[0041] Experimental results: See Table 3 for details.

[0042] Table 3: Test Results of Example 3

[0043] In this embodiment, the QMA column desalting step was omitted after purification, resulting in the retention of residual inorganic salts in the reaction system. A high ionic strength environment accelerates the hydrolysis and decomposition of radioactive compounds, while also affecting the physicochemical stability and biocompatibility of the formulation. Consequently, the product has low radiochemical purity and exhibits significant degradation during storage.

[0044] Example 4 This embodiment provides a method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer, the specific implementation steps of which include: Experimental materials: Methyl 2-(tert-Butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate, N,N-bis(trifluoromethanesulfonyl)aniline, triethylamine, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride, pinacol diboronate, potassium acetate, trifluoromethanesulfonic anhydride, 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane and potassium fluoride (fluorine-18 F), FBPA eluent, 1 mL acetonitrile for column loading, precursor, copper tetrapyridine trifluoromethanesulfonate, DMF, pyridine, 12M hydrochloric acid, 7M sodium hydroxide, ascorbic acid, deionized water, mobile phase acetate-sodium acetate buffer.

[0045] Experimental objective: Preparation of LAT1-targeted 18 F-labeled boron phenylalanine PET tracer was used to investigate the combined effect of multi-parameter degradation on the product by simultaneously changing the neutralization pH, purification column type, and elution conditions. Experimental steps: S1: A mixture of methyl 2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate, N,N-bis(trifluoromethylsulfonyl)aniline, and triethylamine was dissolved in dichloromethane. The mixture was then stirred and reacted at 0°C for 1.5 h, and then the mixture was brought back to room temperature and reacted at 25°C for 1 h. The solvent was then rotary evaporated to obtain methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate. S2: Methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride, pinacol diboronate, and potassium acetate prepared in S1 were dissolved in 1,4-dioxane solvent. The system was then heated to 120°C and reacted for 12 hours. The solvent was then rotary evaporated to obtain methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate. S3: Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate, dibenzo[b,d]thiophene 5-oxide, and trifluoromethanesulfonic anhydride prepared in S2 were dissolved in dichloromethane and reacted at -40°C for 30 minutes, followed by reaction at room temperature of 25°C for 30 minutes. The solvent was then rotary evaporated to obtain 5-(2-(2-amino-3-methoxy-3-oxopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonic acid onium; S4: The 5-(2-(2-amino-3-methoxy-3-oxopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborane-2-yl)phenyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate, 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane, and potassium fluoride (fluorine- 18F) was dissolved in acetonitrile, and the system was then heated to 110°C and reacted for 20 minutes. The solvent was then rotary evaporated to obtain 2-amino-3-(2-(fluoro-) 18 Methyl F)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate; S5: The 2-amino-3-(2-(fluoro-) obtained last in S4 18 Methyl F)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate was dissolved in 12M hydrochloric acid, and then heated to 110°C for 10 minutes to give 2-amino-3-(2-(fluoro- 18 F)-4-Borate-phenyl)propionic acid; S6: After the final product of S5 has cooled to room temperature, slowly add 7M sodium hydroxide solution and adjust the pH of the system to 4.0 and stir thoroughly for 10 minutes; S7: After the product reaction in S6 is complete, add deionized water at a ratio of 1:3 and mix thoroughly. Then, place this mixture on a C8 column with a mobile phase of 0.1% acetic acid / 10% acetonitrile and a flow rate of 1.5 mL / min for isocratic elution and finally collect the liquid. S8: The final solution collected in S7 is desalted and concentrated using a QMA anion exchange column. The column is then rinsed with physiological saline to collect the liquid. The concentrated solution and the liquid obtained from the saline rinse are filtered through a 0.22 μm sterile filter membrane to obtain... 18 F-FBPA injection.

[0046] Experimental results: See Table 4 for details.

[0047] Table 4: Test Results of Example 4

[0048] This embodiment simultaneously employs a C8 column, high acetonitrile ratio (10%) elution, and pH 3.0 neutralization conditions. The C8 column has relatively weak retention capacity for the target analyte; the high organic phase further shortens the retention time, resulting in… 18 F-FBPA was not completely separated from polar impurities; although a low pH could inhibit defluorination, it may lead to carboxyl protonation, which would change the chromatographic behavior. Multiple deteriorating conditions together caused a significant decrease in purification efficiency, resulting in the lowest product purity and yield.

[0049] Example 5 This embodiment provides a method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer, the specific implementation steps of which include: Experimental materials: Methyl 2-(tert-Butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate, N,N-bis(trifluoromethanesulfonyl)aniline, triethylamine, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride, pinacol diboronate, potassium acetate, trifluoromethanesulfonic anhydride, 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane and potassium fluoride (fluorine- 18 F), FBPA eluent, 1 mL acetonitrile for column loading, precursor, copper tetrapyridine trifluoromethanesulfonate, DMF, pyridine, 12M hydrochloric acid, 7M sodium hydroxide, ascorbic acid, deionized water, mobile phase acetate-sodium acetate buffer.

[0050] Experimental objective: Preparation of LAT1-targeted 18 The effect of F-labeled boron phenylalanine PET tracer on product purity was investigated by changing the neutralization pH conditions. Experimental steps: S1: A mixture of methyl 2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate, N,N-bis(trifluoromethylsulfonyl)aniline, and triethylamine was dissolved in dichloromethane. The mixture was then stirred and reacted at 0°C for 1.5 h, and then the mixture was brought back to room temperature and reacted at 25°C for 1 h. The solvent was then rotary evaporated to obtain methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate. S2: Methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride, pinacol diboronate, and potassium acetate prepared in S1 were dissolved in 1,4-dioxane solvent. The system was then heated to 120°C and reacted for 12 hours. The solvent was then rotary evaporated to obtain methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate. S3: Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate, dibenzo[b,d]thiophene 5-oxide, and trifluoromethanesulfonic anhydride prepared in S2 were dissolved in dichloromethane and reacted at -40°C for 30 minutes, followed by reaction at room temperature of 25°C for 30 minutes. The solvent was then rotary evaporated to obtain 5-(2-(2-amino-3-methoxy-3-oxopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonic acid onium; S4: The 5-(2-(2-amino-3-methoxy-3-oxopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborane-2-yl)phenyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate, 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane, and potassium fluoride (fluorine- 18 F) was dissolved in acetonitrile, and the system was then heated to 110°C and reacted for 20 minutes. The solvent was then rotary evaporated to obtain 2-amino-3-(2-(fluoro-) 18 Methyl F)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate; S5: The 2-amino-3-(2-(fluoro-) obtained last in S4 18 Methyl F)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate was dissolved in 12M hydrochloric acid, and then heated to 110°C for 10 minutes to give 2-amino-3-(2-(fluoro- 18 F)-4-Borate-phenyl)propionic acid; S6: After the final product of S5 has cooled to room temperature, slowly add 7M sodium hydroxide solution and adjust the pH of the system to 6.5 and stir thoroughly for 10 minutes; S7: After the product reaction in S6 is complete, add deionized water at a ratio of 1:3 and mix thoroughly. Then, place this mixture on a C18 column with a mobile phase of 0.1% acetic acid / 1% acetonitrile and a flow rate of 1 mL / min for isocratic elution and finally collect the liquid. S8: The final solution collected in S7 is desalted and concentrated using a QMA anion exchange column. The column is then rinsed with physiological saline to collect the liquid. The concentrated solution and the liquid obtained from the saline rinse are filtered through a 0.22 μm sterile filter membrane to obtain... 18 F-FBPA injection.

[0051] Experimental results: See Table 5 for details.

[0052] Table 5: Test Results of Example 5

[0053] In this embodiment, the neutralization pH is adjusted to 6.5 (slightly alkaline), under which conditions the benzene ring... 18 F readily undergoes nucleophilic substitution or elimination reactions, causing radioactive fluorine to be released. Meanwhile, the phenylboronic acid structure may undergo hydroxylation or borate esterification in alkaline media, affecting its targeting and stability. Therefore, although the purification and desalting steps are the same as in Example 1, the purity and storage stability of the product are still significantly reduced.

[0054] Comparative Example 1 This embodiment provides a method for preparing a conventional labeled boron phenylalanine PET tracer, the specific implementation steps of which include: Experimental materials: 4-Borate-L-phenylalanine (BPA), [18F]potassium fluoride / K2.2.2 complex, acetonitrile, hydrochloric acid, sodium hydroxide, physiological saline, C18 solid-phase extraction column, 0.22 μm sterile filter membrane.

[0055] Experimental objective: Prepared using the traditional direct fluorination method 18 F-labeled boron phenylalanine.

[0056] Experimental steps: S1: Will 18 O water target irradiation 18 F-fluoride ions were captured using a K2.2.2 complex, followed by azeotropic dehydration with acetonitrile to obtain a dry product. 18 F potassium fluoride / K2.2.2 complex; S2: Dissolve 5 mg of 4-boronic acid-L-phenylalanine in 1 mL of acetonitrile, and add it to the above-mentioned dry... 18 In F fluoride, the reaction is carried out at 100°C for 15 minutes; S3: After the reaction is complete, cool to room temperature, add 5 mL of water to dilute, pass through a C18 solid phase extraction column, wash with water and 10% ethanol aqueous solution, and finally elute the radioactive product with 1 mL of ethanol. S4: Dry the ethanol eluent under a nitrogen stream, reconstitute with physiological saline, and filter through a 0.22 μm sterile membrane to obtain... 18 F-FBPA injection.

[0057] Experimental results: See Table 6 for details.

[0058] Table 6: Test Results of Comparative Example 1

[0059] Traditional methods use unprotected 4-boronic acid-L-phenylalanine directly with 18 Nucleophilic substitution reactions of F-fluorides are highly inefficient because the boric acid groups, which are not protected, are prone to forming dimers or undergoing deboronization side reactions in the reaction system. Furthermore, purification relies solely on simple C18 solid-phase extraction, which cannot effectively remove unreacted precursors, boric acid byproducts, and inorganic impurities.

[0060] Example 1 employed optimized conditions of pH 4.0 neutralization, C18 column purification, and QMA column desalting to achieve high radiochemical purity, high radiochemical yield, and good stability, making it suitable for clinical PET imaging.

[0061] Example 2 used the same neutralization and desalting steps, but increased the acetonitrile ratio to 5% and increased the flow rate, resulting in incomplete HPLC separation, co-collection of impurities, and a decrease in radiochemical purity to about 82%, as well as a decrease in yield.

[0062] Example 3 omitted the QMA column desalting step, resulting in high inorganic salt residue in the product, which accelerated radioactive decomposition, with a radiochemical purity of only about 78% and a significant decrease in stability.

[0063] Example 4 employed acid neutralization, a C8 column, and a high acetonitrile ratio for elution. Multiple deterioration conditions led to a significant reduction in purification efficiency, with radiochemical purity at only about 72% and the lowest yield.

[0064] Example 5 used the same purification and desalting steps, but due to the alkaline neutralization pH, some ^18^F was lost, resulting in a decrease in radiochemical purity to about 86% and reduced stability.

[0065] Comparative Example 1 uses the traditional direct fluorination method, that is, using unprotected 4-boronic acid-L-phenylalanine as a precursor and 18 The F fluoride reaction, purified by simple C18 solid-phase extraction, showed that the radiochemical purity of the method was only 45%, the radiochemical yield was 6%, the specific activity was only 15 GBq / μmol, and the stability of the product decreased significantly to 40% after 4 hours.

[0066] The above description is merely a specific embodiment of this application, but the scope of protection of this application is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in this application should be included within the scope of protection of this application. Therefore, the scope of protection of this application should be determined by the scope of protection of the claims.

[0067] In conclusion, the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer, characterized in that, Specifically, the following steps are included: S1: A mixture of methyl 2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate, N,N-bis(trifluoromethylsulfonyl)aniline, and triethylamine was dissolved in dichloromethane. The mixture was then stirred and reacted at 0°C, and then allowed to return to room temperature. The solvent was then rotary evaporated to obtain methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate. S2: Methyl 2-(tert-butoxycarbonylamino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propionate, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride, pinacol diboronate, and potassium acetate prepared in S1 are dissolved in 1,4-dioxane solvent. The system is then heated to react, and the solvent is then rotary evaporated to obtain methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate; S3: Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate, dibenzo[b,d]thiophene 5-oxide, and trifluoromethanesulfonic anhydride prepared in S2 were dissolved in dichloromethane and reacted at sub-zero temperature for 30 minutes. Then, the mixture was reacted at room temperature for 30 minutes, and the solvent was then rotary evaporated to obtain 5-(2-(2-amino-3-methoxy-3-oxopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonic acid onium; S4: The 5-(2-(2-amino-3-methoxy-3-oxopropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborane-2-yl)phenyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate, 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane, and potassium fluoride (fluorine- 18 F) was dissolved in acetonitrile, and the system was then heated to react. The solvent was then rotary evaporated to give 2-amino-3-(2-(fluoro-) 18 Methyl F)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate; S5: The 2-amino-3-(2-(fluoro-) obtained last in S4 18 Methyl F)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)propionate was dissolved in 12M hydrochloric acid, and then heated to react and give 2-amino-3-(2-(fluoro- 18 F)-4-Borate-phenyl)propionic acid; S6: After the final product of S5 has cooled to room temperature, slowly add 7M sodium hydroxide solution and stir thoroughly for 10 minutes; S7: After the product reaction in S6 is complete, add deionized water at a ratio of 1:3 and mix thoroughly. Then place this mixture on a C18 column for isocratic elution and finally collect the liquid. S8: The final solution collected in S7 is desalted and concentrated using a QMA anion exchange column. The column is then rinsed with physiological saline to collect the liquid. The concentrated solution and the rinsing liquid are filtered through a sterile membrane to obtain... 18 F-FBPA injection solution should be stored at low temperature.

2. The method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer as described in claim 1, characterized in that, In S1, methyl 2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propionate, N,N-bis(trifluoromethylsulfonyl)aniline, and triethylamine were dissolved in dichloromethane and then stirred at 200 rpm for 1.5 h at 0 °C. After that, the mixture was restored to room temperature of 25 °C and stirred at 200 rpm for 1 h.

3. The method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer as described in claim 1, characterized in that, In S2, the final product prepared in S1, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride, pinacol diborate, and potassium acetate were dissolved in 1,4-dioxane solvent and then heated to 120°C and stirred at 200 rpm for 2 hours.

4. The method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer as described in claim 1, characterized in that, In S3, the final product prepared in S2, dibenzo[b,d]thiophene 5-oxide, and trifluoromethanesulfonic anhydride were dissolved in dichloromethane and then stirred continuously at 200 rpm for 30 minutes at -40°C. Then, the mixture was stirred at 200 rpm for 30 minutes at room temperature of 25°C.

5. The method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer as described in claim 1, characterized in that, In S4, the final product obtained in S3, 4,7,13,16,21,24-hexaoxo-1,10-diazabicyclo[8.8.8]hexacosane, and potassium fluoride (fluorine- 18 F) was dissolved in acetonitrile, and then placed at 110°C and stirred continuously at 200 rpm for 20 minutes.

6. The method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer as described in claim 1, characterized in that, In step S5, the final product obtained in step S4 was dissolved in a 12M hydrochloric acid solution, and the system was then heated to 110°C and stirred continuously for 10 minutes.

7. The method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer as described in claim 1, characterized in that, In S6, 7M sodium hydroxide solution is slowly added dropwise to the final product obtained after cooling S5 until the pH of the system is 4.0~4.

5.

8. The method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer as described in claim 1, characterized in that, In step S7, deionized water was added to the final product obtained in step S6 at a ratio of 1:3, and the mixture was then placed on a C18 column with a mobile phase of 0.1% acetic acid / 1~10% acetonitrile and a flow rate of 1 mL / min for moderate elution.

9. The method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer as described in claim 1, characterized in that, In step S8, the collected liquid is filtered through a 0.22 μm sterile filter membrane to obtain 18F-FBPA injection solution.

10. The method for preparing a LAT1-targeted 18F-labeled boron phenylalanine PET tracer as described in claim 1, characterized in that, In S8, 18F-FBPA is stored in a low-temperature, oxygen-free environment at -20 to -10°C.

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