A method for preparing 225Ac and 212Pb photo-nuclear reaction by regulating inhibition of 210Pb impurities

Abstract

The application discloses a kind of 225Ac and 212Pb photodisintegration preparation methods for regulating and inhibiting 210Pb impurities, belong to nuclear technology application and radioisotope preparation field.For existing 226 Ra photodisintegration preparation process 210 Pb Impurity is difficult to inhibit the key technical problem, the application utilizes 226 Ra (gamma, n), (gamma, 2n), (gamma, 4n) three reaction channels threshold difference, the energy of electron beam is accurately controlled in 38~42MeV interval, so that target reaction is fully excited and impurity reaction is relatively inhibited.Monte Carlo simulation results show that, under 40MeV optimization condition 210 Pb Activity is reduced by 60.7% compared with 50MeV condition, 210 Pb / 212 Pb Activity ratio is 1.31×10 ‑5 , while 225Ac and 212Pb yield is retained 96.2% and 94.6% respectively, and radioactivity purity is all ≥99.998%.The application only realizes impurity inhibition by process parameter regulation, engineering implementation cost is low, repeatability is strong, suitable for large-scale industrial popularization.

Description

Technical Field

[0001] This invention belongs to the field of nuclear technology application and radiomedical isotope preparation technology, specifically involving a method for preparing 225Ac and 212Pb by photonuclear reaction with controlled suppression of 210Pb impurities. Background Technology

[0002] Radioactive medical isotopes 225 Ac and 212 Pb is one of the two most promising alpha emitter nuclides for clinical application in the field of targeted alpha therapy (TAT). Targeted alpha therapy utilizes the high linear energy transfer density (LET) of alpha particles to generate dense ionizing radiation within tumor cells, leading to DNA double-strand breaks and thus highly effective killing of tumor cells while causing minimal damage to surrounding normal tissues. 225 Ac has a half-life of 9.92 days, and its decay chain releases four alpha particles sequentially, eventually forming a stable alpha particle. 209 Bi can release a high energy of about 28 MeV per atom, which can produce a sustained and efficient killing effect on tumor cells, making it particularly suitable for the treatment of solid tumors and micrometastases. 212 The half-life of Pb is 10.64 hours, which is considered... 212 The Bi nucleus can continuously supply alpha emitters during tumor-targeted delivery. 212 Bi, with its shorter half-life, can reduce the whole-body radiation dose to patients. Currently, based on 225 Ac and 212 Pb-targeting alpha drugs have demonstrated breakthrough efficacy in clinical trials for various malignant tumors, including prostate cancer, neuroendocrine tumors, and melanoma. Some drugs have entered Phase III clinical trials and are expected to be approved for marketing in the next few years. However, 225 Ac and 212 The severe global shortage of Pb has become a key bottleneck restricting the development and clinical application of targeted alpha therapy.

[0003] at present, 225 Ac and 212 The main methods for preparing phosphorus (Pb) include reactor irradiation, proton accelerator preparation, and electron accelerator photonuclear reaction. Reactor irradiation utilizes neutrons generated by a reactor for irradiation. 226 Ra target, through 226 Ra(n, 2n) 225 Ra reaction generates 225 Ac, however, this method has problems such as limited reactor capacity, high nuclear safety requirements, and complex post-target processing, making it difficult to achieve large-scale production. The proton accelerator preparation method utilizes high-energy protons to bombard a thorium or uranium target, generating [the desired product] through a spallation reaction. 225However, this method produces a complex variety of nuclides, which are difficult to separate and purify, and the equipment is expensive, resulting in high operating costs. In contrast, the electron accelerator photonuclear reaction method utilizes an electron accelerator to generate a high-energy electron beam, which is then irradiated with photons by a bremsstrahlung conversion target. 226 Ra target, through 226 Ra(γ,n) 225 Ra→ 225 Ac and 226 Ra(γ, 2n) 224 Ra→ 212 Pb is prepared simultaneously via two reaction pathways. 225 Ac and 212 Pb has unique advantages such as the ability to simultaneously produce two alpha emitter nuclides, good chemical compatibility in irradiation target post-processing, small equipment footprint, low nuclear safety requirements, and ease of large-scale promotion, and has become a research hotspot and key development direction in the current international nuclear medicine field.

[0004] However, existing 226 A key technical problem that is difficult to solve in the Ra photonuclear reaction preparation process is the long-lived isotope impurities. 210 The formation of Pb is difficult to suppress effectively. 210 Pb is obtained through 226 Ra(γ, 4n) 222 The Ra decay chain has a half-life of up to 22.3 years, much longer than... 212 The half-life of Pb is 10.64 hours. Even more seriously, 210 Pb and 212 Pb is an isotope of Pb, possessing identical chemical properties, and cannot be separated from Pb by any chemical means. 212 Removed from Pb products. Once 210 Pb contamination 212 Pb products can create a long-term radiation dose burden in patients, increasing their risk of developing secondary cancers and seriously affecting their health. 212 The radiopurity and clinical safety of Pb-based radiopharmaceuticals are critical concerns. Therefore, how to effectively inhibit... 210 The formation of Pb impurities is... 226 Ra photonuclear reaction preparation 212 The core problem that Pb technology must solve.

[0005] While existing publicly available technical solutions involve the selection of electron accelerator energy parameters, none of them address this issue. 210 Pb impurity suppression is a core technical issue requiring specialized process optimization. For example, CN116741428A discloses a method based on accelerator irradiation... 226The method for simultaneously preparing 225Ac and 212Pb using Ra, while mentioning an electron accelerator energy range of 15–50 MeV, did not provide fine-tuning of the energy parameters or consider the effects of different energies on the production of 225Ac and 212Pb. 210 The influence of Pb impurity formation. CN112885495B discloses "the effect of Pb impurity formation..." 226 "Methods for producing 225Ac from Ra", mainly focusing on 225 The yield and separation and purification methods of Ac were not mentioned at all. 210 The problem lies with Pb impurities. These existing technologies lack physical mechanistic justification for the electron energy selection based on differences in reaction thresholds. They generally employ higher electron energies (e.g., 50 MeV) to pursue high yields of the target nuclide. However, the bremsstrahlung photon spectrum produced by high-energy electron beams has a high proportion of high-energy tails, which can significantly excite... 226 Ra(γ, 4n) reaction, leading to a large amount of 210 Pb impurity formation. Prepared using existing techniques. 212 In Pb products 210 Pb / 212 Pb activity ratio is typically 3 × 10⁻⁶. -5 The above cannot meet the stringent purity requirements for radiopharmaceuticals in clinical nuclear medicine applications (typically requiring ≤2×10⁻⁶). -5 ).

[0006] Furthermore, existing technologies lack effective mechanisms for controlling and protecting electron beam energy stability. The output energy of electron accelerators is susceptible to factors such as grid voltage fluctuations, high-frequency system instability, and equipment aging, causing the actual output energy to deviate from the set value. Even minute energy fluctuations can significantly alter the distribution of the bremsstrahlung photon energy spectrum, leading to… 210 Significant fluctuations in Pb impurity content make it difficult to maintain stable product quality. Furthermore, existing technologies have not optimized the material and thickness of bremsstrahlung conversion targets, resulting in low bremsstrahlung conversion efficiency, low yields of target nuclides, or easy damage to the target material under high-power electron beam bombardment, affecting production continuity.

[0007] In summary, the existing 226 Ra photonuclear reaction preparation 225 Ac and 212 The technical approach for Pb cannot effectively suppress it while ensuring a high yield of the target nuclide. 210 The formation of Pb impurities leads to problems such as low radioactivity purity, unstable quality, and difficulty in meeting clinical application requirements. How can we achieve precise control of process parameters at the source to significantly reduce Pb levels without sacrificing basic production capacity? 210 Improving the activity of Pb impurities and enhancing the radioactive purity and quality stability of products is a pressing technical challenge that needs to be addressed in this field. Summary of the Invention

[0008] The technical problem to be solved by this invention is to address the shortcomings of the prior art by providing a method for the photonuclear reaction preparation of 225Ac and 212Pb with controlled suppression of 210Pb impurities. By precisely controlling the energy of the electron beam output from the electron accelerator within a specific "process sweet spot" range, the method effectively suppresses the excitation of high-threshold reaction channels while maintaining a high yield of the target nuclide. 210 Pb impurity formation, used to solve existing 226 In the Ra photonuclear reaction preparation process 210 Pb impurities are difficult to suppress and have an impact. 212 Technical issues related to the radioactive purity of Pb products.

[0009] The present invention adopts the following technical solution: A method for preparing 225Ac and 212Pb by controlling and suppressing 210Pb impurities via photonuclear reaction includes the following steps: Bremsstrahlung photon irradiation generated by an electron beam passing through a bremsstrahlung conversion target 226 Ra target, through 226 Ra(γ,n) reaction generates 225 Ra decays to 225 Ac, and through 226 Ra(γ, 2n) reaction generates 224 Ra decays to 212 Pb, for the simultaneous preparation of medical isotopes 225 Ac and 212 Pb; wherein, the electron beam energy range of the electron accelerator output is 38~42MeV, making 226 The Ra(γ,4n) reaction was inhibited, and the resulting irradiated products contained... 210 Pb activity and 212 The ratio of Pb activity ≤ 2 × 10 -5 .

[0010] Preferably, the electron beam is output by an accelerating device with a rated power of 60kW and a rated energy range of 30~50MeV. In production mode, the electron energy is locked in a preset range of 38~42MeV. The accelerating device includes an online electron energy monitoring device and an interlocking protection device, which automatically cuts off the beam when the electron energy deviates from the set value by more than ±2%.

[0011] Preferably, the electron beam energy stability is controlled within ±1%, and real-time regulation is achieved through the high-frequency voltage closed-loop feedback system of the acceleration device.

[0012] Preferably, the bremsstrahlung conversion target is a tantalum target.

[0013] Preferably, the longitudinal thickness of the tantalum target is 3 mm.

[0014] Preferably, the 226 The Ra target charge is 1g, the electron beam power is 60kW, and the irradiation duration is 10 days.

[0015] Preferably, the 226 The Ra target is covered with an aluminum cladding for physical isolation and initial sealing during the irradiation process.

[0016] Preferably, the prepared 225 The radioactivity purity of Ac products is ≥99.998%.

[0017] Preferably, the prepared 212 The radioactive purity of Pb products is ≥99.998%.

[0018] Another technical solution of the present invention is that the preparation method described above yields... 225 Ac and / or 212 Application of Pb in the preparation of radiopharmaceuticals for targeted alpha therapy.

[0019] Compared with the prior art, the present invention has at least the following beneficial effects: A method for preparing 225Ac and 212Pb by controlling and suppressing 210Pb impurities through photonuclear reaction. 226 The Ra(γ,n) reaction threshold is approximately 6.4 MeV, the (γ,2n) reaction threshold is approximately 11.4 MeV, and the (γ,4n) reaction threshold is approximately 20 MeV or higher. By precisely controlling the electron beam energy within the 38~42 MeV range, the bremsstrahlung photon energy spectrum can be used to fully excite the first two target reaction channels, while relatively suppressing the high-threshold (γ,4n) impurity reaction channel. 210 Pb and 212 Pb is an isotope and cannot be separated by any chemical means; existing technologies can only passively accept impurity levels after irradiation. This invention actively cuts off the impurity formation pathway through energy modulation, enabling… 210 Pb / 212 Pb activity ratio was strictly controlled at 2×10⁻⁶. -5 Within this range, the long lifespan has been completely eliminated. 210 The long-term radiation dose burden caused by Pb. At the same time, the yield of the target nuclide did not decrease significantly within this range, achieving a balance between production capacity and purity, and breaking through the technical bottleneck that high yield inevitably comes with high impurities in existing technologies.

[0020] Furthermore, the parameter matching of a rated power of 60kW and a rated energy range of 30~50MeV ensures that the device can output a high-energy electron beam that meets process requirements while also having sufficient adjustment margin. The energy lock function in production mode prevents energy deviation caused by misoperation, while the ±2% deviation automatic interlock protection device immediately cuts off the beam current in case of energy abnormality. This invention's dual mechanism of energy lock and interlock protection ensures that the electron beam energy remains stable within the process sweet spot range of 38~42MeV during production, significantly improving process repeatability and product quality consistency, and reducing quality risks during production. Furthermore, even minute fluctuations in electron beam energy significantly affect the distribution of the bremsstrahlung photon energy spectrum, thereby altering the excitation ratio of each reaction channel. ±1% stability control ensures that the (γ, 4n) reaction channel remains suppressed even during prolonged continuous irradiation. 210 The Pb impurity content will not fluctuate abnormally. Meanwhile, the closed-loop feedback system can automatically compensate for the effects of external factors such as power grid fluctuations and equipment heating, requiring no manual intervention and improving the automation level and operational efficiency of the production process.

[0021] Furthermore, tantalum materials possess high atomic number, high melting point, good thermal conductivity, and radiation resistance. High atomic number materials can more efficiently convert electron beam energy into bremsstrahlung photons, increasing photon yield; the high melting point and good thermal conductivity allow it to withstand bombardment by a 60kW high-power electron beam without melting; and the radiation resistance extends the lifespan of the target material. Using low atomic number materials such as aluminum results in low bremsstrahlung conversion efficiency, leading to a significant decrease in the yield of the target nuclide; if other high atomic number materials such as tungsten are used, their processing performance and thermal shock resistance are inferior to tantalum, making them prone to cracking and damage under high-power electron beam bombardment. The choice of a tantalum target ensures stable operation and a constant photon yield during 10 days of continuous irradiation, guaranteeing a high yield of the target nuclide.

[0022] Furthermore, the 3mm tantalum target can almost completely absorb electron beams of 38–42 MeV while minimizing photon self-absorption. This maximizes the proportion of medium-energy photons capable of exciting (γ,n) and (γ,2n) reactions in the generated bremsstrahlung photon energy spectrum, while the proportion of high-energy photons capable of exciting (γ,4n) reactions is relatively low. This further enhances the impurity suppression effect while ensuring a high yield of the target nuclide.

[0023] Furthermore, 1g 226 The Ra target loading is currently a relatively economical and reasonable scale for industrial production, achieving sufficient nuclide yield without posing excessive nuclear safety risks. The 60kW beam power matches the rated power of the electron accelerator, fully utilizing the equipment's production capacity. The 10-day irradiation duration is close to...225 The half-life of Ac is 9.92 days. 225 Ac irradiation production is nearing saturation; further extending irradiation time will have limited effect on increasing production and may even increase output. 210 Accumulation of Pb impurities.

[0024] Furthermore, 226 Ra is a highly radioactive nuclide whose decay produces radon gas, which is volatile and can cause serious radioactive contamination if leaked. The aluminum cladding provides physical isolation and initial sealing, effectively preventing... 226 The leakage of Ra and its decay products ensures nuclear safety during the production process. At the same time, the low absorption characteristics of the aluminum cladding to photons will not significantly affect the irradiation effect of bremsstrahlung photons on the 226Ra target, ensuring that the yield of the target nuclide remains unaffected.

[0025] Furthermore, 225 When Ac is used for targeted alpha therapy, its radioactive purity directly affects the treatment effect and patient prognosis. A radioactive purity of 99.998% means that the number of impurity atoms per million atoms does not exceed two, far exceeding the product quality level of existing technologies. This makes the product prepared by this invention... 225 Ac products can be used directly in the preparation of clinical radiopharmaceuticals without further purification, simplifying the subsequent production process and reducing production costs.

[0026] Furthermore, suppressing it at the source 210 The formation of Pb impurities makes 212 The radioactivity purity of the Pb product reached over 99.998%, completely eliminating... 210 The long-term radiation dose burden caused by Pb. This makes 212 Pb can be safely used in clinical targeted alpha therapy, providing a new and effective means of treating malignant tumors.

[0027] By directly linking the preparation method of this invention to downstream clinical applications, the scope of patent protection is expanded. Targeted alpha therapy is currently a research hotspot in the field of tumor treatment. 225 Ac and 212 The market demand for Pb is huge. The protection afforded by this claim extends to any product prepared using the method of this invention. 225 Ac and 212 The use of phosphorus (Pb) in the preparation of targeted alpha therapeutics will fall within the scope of patent protection, effectively safeguarding the inventor's intellectual property rights. At the same time, this lays a legal foundation for subsequent technology transfer and industrial application.

[0028] In summary, this invention suppresses electron beam energy at its source through precise control. 210The generation of Pb impurities achieves a synergistic optimization of high yield and high purity. The process is simple and easy to promote, and can simultaneously prepare two clinically urgently needed α nuclides, effectively alleviating the shortage of medical isotopes.

[0029] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0030] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the following description of the relative embodiments will be briefly introduced. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0031] Figure 1 Provided for embodiments of the present invention 226 Ra photonuclear reaction preparation 225 Ac and 212 A schematic diagram of the longitudinal layout of the Pb electron accelerator target system, where 1 represents the electron beam generated by the electron accelerator, 2 represents the tantalum conversion target, 3 represents the aluminum cladding, and 4 represents... 226 Ra target; Figure 2 for 226 A comparison curve of the photon nucleus reaction cross section of the three reaction channels Ra (γ,n), (γ,2n), and (γ,4n) as a function of photon energy; Figure 3 The irradiation end time in the embodiments and comparative examples of the present invention. 225 Ac output, 227 A comparison curve of Ac impurity activity as a function of electron energy (30~50MeV); Figure 4 The irradiation end time in the embodiments and comparative examples of the present invention. 212 Pb production, 210 A comparison curve of Pb impurity activity as a function of electron energy (30~50MeV).

[0032] Among them, 1. electron accelerator; 2. tantalum conversion target; 3. aluminum cladding; 4. 226 Ra target; Detailed Implementation The technical solution of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0033] Unless otherwise specified, all embodiments and preferred embodiments mentioned herein can be combined to form new technical solutions.

[0034] Unless otherwise specified, all the technical features and preferred features mentioned herein can be combined to form new technical solutions.

[0035] In this invention, unless otherwise specified, percentage (%) or parts refer to weight percentage or parts relative to the composition.

[0036] Unless otherwise specified, the components or preferred components involved in this invention can be combined with each other to form new technical solutions.

[0037] In this invention, unless otherwise specified, the numerical range "a~b" represents an abbreviation of any combination of real numbers between a and b, where a and b are both real numbers. For example, the numerical range "6~22" means that all real numbers between "6~22" have been listed in this document, and "6~22" is simply an abbreviation of these numerical combinations.

[0038] The "scope" disclosed in this invention can be in the form of a lower limit and an upper limit, and can be one or more lower limits and one or more upper limits, respectively.

[0039] In this invention, the term "and / or" as used herein refers to any combination of one or more of the associated listed items, as well as all possible combinations, and includes such combinations.

[0040] In this invention, unless otherwise stated, the various reactions or operation steps may be performed sequentially or in a particular order. Preferably, the reaction methods described herein are performed sequentially.

[0041] Unless otherwise stated, the technical and scientific terms used herein have the same meanings as those familiar to those skilled in the art. Furthermore, any methods or materials similar to or equivalent to those described herein may also be used in this invention.

[0042] This invention provides a method for preparing 225Ac and 212Pb by photonuclear reaction with controlled suppression of 210Pb impurities, utilizing... 226 The invention leverages the significantly different physical characteristics of the three reaction channels Ra(γ,n), (γ,2n), and (γ,4n) (approximately 6.4, 11.4, and above 20 MeV, respectively) to precisely control the output electron beam energy of the electron accelerator within a preset range of 38–42 MeV. This ensures the full excitation of the first two reactions while relatively suppressing the (γ,4n) reaction. This invention achieves impurity suppression solely through process parameter control, resulting in low engineering implementation costs, high repeatability, and suitability for large-scale industrial application.

[0043] Please see Figure 1 The present invention provides a regulatory inhibition 210 Pb impurities 225 Ac and 212 The Pb photonuclear reaction preparation apparatus, along the electron beam propagation direction, comprises, in sequence: an electron accelerator 1, a tantalum conversion target 2, an aluminum cladding 3, and... 226 Ra target 4. The output electron beam energy of the electron accelerator 1 is precisely controlled within a preset range of 38~42MeV.

[0044] Electron Accelerator 1: Rated energy range 30~50MeV, production mode electron energy 40MeV, electron energy stability ±1%, beam power 60kW, equipped with an online electron energy monitoring device and a ±2% deviation automatic interlock protection device.

[0045] Tantalum conversion target 2: longitudinal thickness 3mm.

[0046] Aluminum cladding 3: Covered in 226 The outer surface of the Ra target is used for physical isolation and initial sealing during the irradiation process.

[0047] 226 Ra target 4: 1g of material.

[0048] This invention discloses a method for preparing 225Ac and 212Pb by controlling and suppressing 210Pb impurities through photonuclear reactions, comprising the following steps: The electron beam energy output from the electron accelerator is controlled within the range of 38–42 MeV, and the stability of the electron beam energy is precisely limited to within ±1%. This is achieved through real-time regulation via the accelerator's high-frequency voltage closed-loop feedback system. The bremsstrahlung conversion target is a tantalum target with a thickness of 3 mm. 226 The Ra target charge was 1g, the electron beam current power was 60kW, the irradiation duration was 10 days, and the resulting irradiation products included... 210 Pb activity and 212 The Pb activity ratio was controlled at 2×10. -5 the following.

[0049] When the electron beam energy is precisely controlled within the 38~42MeV range, due to 226 The Ra(γ,n) response threshold is approximately 6.4 MeV. 226 The Ra(γ, 2n) reaction threshold is approximately 11.4 MeV. 226 The Ra(γ,4n) reaction threshold is approximately above 20 MeV. The bremsstrahlung photon energy spectrum generated by the electron beam within this process range precisely excites the first two reactions while relatively suppressing the (γ,4n) reaction. Under this mechanism, the resulting irradiated products contain... 210 Pb activity decreased from 2.22 × 10⁻⁶ under 50 MeV conditions. 7 Bq was significantly reduced to 8.72 × 10⁻⁶ under 40 MeV conditions.6 Bq decreased by 60.7%; 210 Pb / 212 The Pb activity ratio was 3.17 × 10⁻⁶ under 50 MeV conditions. -5 Strictly controlled at 1.31×10 under 40MeV conditions. -5 Within. 225 Ac output was only 2.10 × 10⁻⁶ for the 50 MeV condition. 11 Bq is slightly reduced to 2.02 × 10⁻⁶ at the 40 MeV operating condition. 11 Under the premise of Bq (retention rate of 96.2%), the basic production capacity and product radioactivity purity were synergistically optimized.

[0050] Please see Figure 2 It showed 226 The physical characteristics of the three reaction channels Ra (γ,n), (γ,2n), and (γ,4n) with significant differences in threshold values, with (γ,n) threshold value of approximately 6.4 MeV, (γ,2n) threshold value of approximately 11.4 MeV, and (γ,4n) threshold value of approximately 20 MeV or higher, form the physical basis for the fine-tuning of electron energy in this invention.

[0051] Monte Carlo simulation studies show that 226 Ra has three main reaction pathways in the photonic nuclear reaction: 226 Ra(γ,n) 225 The Ra reaction threshold is approximately 6.4 MeV. 226 Ra(γ, 2n) 224 The Ra reaction threshold is approximately 11.4 MeV. 226 Ra(γ, 4n) 222 The Ra reaction threshold is approximately 20 MeV or higher. 225 Ra via β - decay to form the target nuclide 225 Ac; 224 Ra undergoes multiple decay steps to generate the target nuclide. 212 Pb; and 222 Ra undergoes multiple decay steps to generate impurity nuclides. 210 Pb. To address the significant differences in threshold values ​​within this reaction channel, this embodiment precisely controls the energy of the electron beam output from the electron accelerator within a preset range of 38–42 MeV. If the electron energy is too low (e.g., below 38 MeV), it will lead to… 225 Ac and 212 The significant decline in Pb production impacts basic production capacity; if the electron energy is too high (e.g., above 42 MeV), the high-energy tail of the bremsstrahlung photon spectrum will significantly increase, exciting the (γ, 4n) reaction to generate a large amount of Pb. 210Pb impurities. Meanwhile, the electron beam energy stability is precisely controlled within ±1%, adjusted in real time via the accelerator's high-frequency voltage closed-loop feedback system.

[0052] The preparation method of this invention yields 225 Ac and / or 212 Application of Pb in the preparation of radiopharmaceuticals for targeted alpha therapy.

[0053] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. The components of the embodiments of the present invention described and shown in the accompanying drawings can generally be arranged and designed in various different configurations. Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0054] 1. Experimental Apparatus and General Materials All embodiments and comparative examples used the same experimental setup, arranged sequentially along the electron beam propagation direction: electron accelerator, bremsstrahlung conversion target, aluminum cladding, and... 226 Ra target. Among them: Electron accelerator: Rated power 60kW, rated energy range 30~50MeV, equipped with an online electron energy monitoring device and an automatic interlock protection device for ±2% deviation, and achieves real-time control of electron beam energy stability ±1% through a high-frequency voltage closed-loop feedback system; Bremsstrahlung conversion target: A tantalum target with a longitudinal thickness of 3 mm is used; 226 A target: 1g of charge, with an aluminum cladding on the outside, used for physical isolation and initial sealing during the irradiation process.

[0055] 2. General process parameters Except for the electron beam output energy, all embodiments and comparative examples used the exact same process parameters: Electron beam power: 60kW; Irradiation duration: 10 consecutive days; Target system layout: The electron beam output end is positioned opposite the tantalum conversion target. 226 Target a is located downstream of the tantalum conversion target.

[0056] 3. Performance Testing Methods Nuclide activity detection: High-purity germanium gamma spectrometer was used to perform energy dispersive spectroscopy analysis on the irradiated products at the end of irradiation to quantitatively determine the irradiation activity. 225 Ac、 212 Pb, 227 c. 210 The activities of the four Pb nuclides; Radioactivity purity calculation: Radioactivity purity = Target nuclide activity / Total radioactivity of irradiated products × 100%; Impurity ratio calculation: 210 Pb / 212 Pb activity ratio = 210 Pb activity 212 Pb activity; Data source: All nuclide yield data were obtained through Monte Carlo simulation calculations and verified experimentally. The deviation between simulation results and experimental results is ≤5%.

[0057] Example 1: Electron beam energy 38MeV condition The experimental setup was constructed according to the above general instructions. The output energy of the electron accelerator was set to 38 MeV. The energy range was locked in production mode. The electron beam was started for continuous irradiation. Irradiation was stopped after 10 days, and the irradiation products were collected.

[0058] Performance test results: 225 Ac output: 1.98 × 10 11 Bq (reaching 94.3% of the peak output of 50MeV); 212 Pb yield: 6.38 × 10 11 Bq (reaching 91.0% of the peak output of 50MeV); 227 c impurity activity: 3.67 × 10 6 q; 210 Pb impurity activity: 5.57 × 10 6 Bq; 210 Pb / 212 Pb activity ratio: 8.73 × 10 -6 2×10 -5 (meets the requirements) 225 Ac radioactivity purity: ≥99.998%; 212 Pb radioactivity purity: ≥99.998%.

[0059] In this embodiment, even under the lower limit of electron beam energy, the yield of the target nuclide remains above 90% of its peak value. 210The activity of Pb impurities is at a low level, which fully meets the purity requirements for large-scale production and clinical drug use.

[0060] Example 2: Electron beam energy 40MeV condition The output energy of the electron accelerator was set to 40 MeV, and the remaining steps were exactly the same as in Example 1.

[0061] Performance test results: 225 Ac output: 2.02 × 10 11 Bq (reaching 96.2% of the peak output of 50MeV); 212 Pb yield: 6.63 × 10 11 Bq (reaching 94.6% of the peak output of 50MeV); 227 c impurity activity: 3.82 × 10 6 q; 210 Pb impurity activity: 8.72 × 10 6 Bq; 210 Pb / 212 Pb activity ratio: 1.31 × 10 -5 (≤2×10) -5 (meets the requirements) 225 Ac radioactivity purity: ≥99.998%; 212 Pb radioactivity purity: ≥99.998%.

[0062] This embodiment represents the optimal process condition of the present invention, compared to the 50MeV comparison condition. 210 The activity of Pb impurities decreased by 60.7%, while 225 Ac production decreased by only 3.8%, achieving the best synergistic optimization between basic production capacity and product radioactivity purity.

[0063] Example 3: Electron beam energy 42MeV condition The output energy of the electron accelerator was set to 42 MeV, and the remaining steps were exactly the same as in Example 1.

[0064] Performance test results: 225 Ac output: 2.05 × 10 11 Bq (reaching 97.6% of the peak output of 50MeV); 212 Pb yield: 6.75 × 10 11 Bq (reaching 96.3% of the peak output of 50MeV); 227 c impurity activity: 3.85 × 10 6 q; 210 Pb impurity activity: 1.22 × 10⁻⁶ 7 q; 210 Pb / 212 Pb activity ratio: 1.81 × 10 -5 (≤2×10) -5 (meets the requirements) 225 Ac radioactivity purity: ≥99.998%; 212 Pb radioactivity purity: ≥99.998%.

[0065] In this embodiment, under the upper limit of electron beam energy, the yield of the target nuclide is close to the peak level, while... 210 Pb / 212 The Pb activity ratio is still controlled within the specified standard and can be used as an alternative process parameter in the capacity-first mode.

[0066] Comparative Example 1: Electron beam energy 30MeV condition The output energy of the electron accelerator was set to 30 MeV, and the remaining steps were exactly the same as in Example 1.

[0067] Performance test results: 225 Ac output: 1.68 × 10 11 Bq (only 80.0% of the peak output of 50MeV); 212 Pb yield: 4.93 × 10 11 Bq (only 70.3% of the peak output of 50MeV); 210 Pb impurity activity: 1.88 × 10 5 ; 210 Pb / 212 Pb activity ratio: 3.81 × 10 -7 Although this proportion 210 Pb impurity activity is extremely low, but the yield of the target nuclide is significantly reduced, which cannot meet the capacity requirements for large-scale preparation and has low industrial application value.

[0068] Comparative Example 2: Electron beam energy 34 MeV condition The output energy of the electron accelerator was set to 34 MeV, and the remaining steps were exactly the same as in Example 1.

[0069] Performance test results: 225 Ac output: 1.84 × 10 11 Bq (only 87.6% of the peak output of 50MeV); 212 Pb production: 5.61 × 10 11 Bq (only 80.0% of the peak output of 50MeV); 210 Pb impurity activity: 5.79 × 10 75 Bq; 210 Pb / 212 Pb activity ratio: 1.03 × 10 -6 Although the yield of the target nuclide has increased compared to the 30MeV operating condition, it still does not meet the requirements for large-scale production, with insufficient capacity per unit time and high production costs.

[0070] Comparative Example 3: Electron beam energy 36 MeV condition The output energy of the electron accelerator was set to 36 MeV, and the remaining steps were exactly the same as in Example 1.

[0071] Performance test results: 225 Ac output: 1.93 × 10 11 Bq (only 91.9% of the peak output of 50MeV); 212 Pb production: 6.10 × 10 11 Bq (only 87.0% of the peak output of 50MeV); 210 Pb impurity activity: 3.56 × 10 6 Bq; 210 Pb / 212 Pb activity ratio: 5.84 × 10 -6 .

[0072] The yield of the target nuclide is still below the 94% threshold for large-scale production, and 210 The activity of Pb impurities begins to rise rapidly, and the overall efficiency of production capacity and purity is lower than that of the process range of this invention.

[0073] Comparative Example 4: Electron beam energy 45 MeV condition The output energy of the electron accelerator was set to 45 MeV, and the remaining steps were exactly the same as in Example 1.

[0074] Performance test results: 225 Ac output: 2.07 × 10 11Bq (only 1.0% increase compared to the 42MeV operating condition); 212 Pb yield: 6.92 × 10 11 Bq (only 2.5% increase compared to the 42MeV operating condition); 210 Pb impurity activity: 1.55 × 10 7 Bq (27.0% increase compared to 42MeV operating condition); 210 Pb / 212 Pb activity ratio: 2.24 × 10 -5 (>2×10) -5 (Does not meet the requirements).

[0075] The yield gain of the target nuclide has reached saturation, but 210 The activity of Pb impurities increased significantly. 210 Pb / 212 The Pb activity ratio exceeded the upper limit, and the product's radioactivity purity could not meet the safety requirements for clinical drug use.

[0076] Comparative Example 5: Electron beam energy of 50 MeV (typical operating condition in existing technology) The output energy of the electron accelerator was set to 50 MeV, and the remaining steps were exactly the same as in Example 1.

[0077] Performance test results: 225 Ac output: 2.10 × 10 11 Bq (peak output); 212 Pb yield: 7.01 × 10 11 Bq (peak output); 210 Pb impurity activity: 2.22 × 10 7 Bq (154.6% increase compared to 40MeV operating condition); 210 Pb / 212 Pb activity ratio: 3.17 × 10 -5 (>2×10) -5 (Does not meet the requirements).

[0078] This comparative example represents a typical high-energy operating condition using existing technologies. Although the target nuclide yield reaches its peak, 210 The sudden increase in Pb impurity activity creates a long-term radiation dose burden, seriously affecting the safety of the product in clinical applications.

[0079] Please see Figure 3 and Figure 4 The 38-42 MeV range represents a high yield range for the target nuclide. 210The dual intersection region of low Pb impurity activity is the core protection scope of this invention; when the electron beam energy output by the electron accelerator is taken as eight specific values ​​of 30, 34, 36, 38, 40, 42, 45, and 50 MeV, while other process parameters remain consistent (tantalum conversion target 3mm, ... 226 When the target charge is 1g, the beam power is 60kW, and the irradiation duration is 10 days, the irradiation end time is... 225 Ac、 212 Pb, 227 Ac、 210 The yield variation patterns of the four Pb nuclides are shown in the table below:

[0080] The above data clearly demonstrates the effectiveness of this invention in the 38-42 MeV embodiment range: 225 Ac's output increased from 1.98 × 10 11 Bq increases to 2.05 × 10 11 Bq, reaching a peak output of 50MeV (2.10×10 11 More than 94.3% of Bq); 212 Pb production increased from 6.38 × 10 11 Bq increases to 6.75 × 10 11 Bq, reaching a peak output of 50MeV (7.01×10⁻⁶). 11 Over 91.0% of Bq); 210 The activity of Pb was strictly controlled at 5.57 × 10⁻⁶. 6 Bq ~ 1.22 × 10 7 The Bq interval corresponds to 210 Pb / 212 The Pb activity ratio was strictly controlled at 8.73 × 10⁻⁶. -6 ~1.81×10 -5 The interval is ≤2×10 -5 Functional limitations.

[0081] When the electron energy is below the lower limit of the sweet spot range of the process of this invention, 38 MeV (corresponding to examples 1-3), although 210 Pb impurities have lower activity, but the target nuclide 225 Ac and 212 Pb production declined significantly under 30MeV operating conditions. 225 Ac's output was only 1.68 × 10 11 Bq, 212 Pb production was only 4.93 × 10⁻⁶. 11 Bq, which is only 80.0% and 70.3% of the 50MeV peak value, respectively, seriously affects basic production capacity and does not meet the capacity requirements for large-scale preparation.

[0082] When the electron energy exceeds the upper limit of the sweet spot range of the process of this invention, 42 MeV (corresponding to ratios 4 and 5), the yield gain of the target nuclide has approached saturation—at the 50 MeV operating condition. 225 Ac yield increased only from 2.05 × 10⁻⁴ to 42 MeV. 11 Bq increased slightly to 2.10 × 10 11 Bq (increase of 2.4%), but 210 The activity of Pb impurities decreased from 1.22 × 10⁻⁶. 7 Bq increased sharply to 2.22 × 10 7 Bq (increase of 82.0%) 210 Pb / 212 Pb activity ratio exceeded 2×10 -5 The functional limitation limit reaches 3.17×10 -5 This cannot meet the stringent purity requirements for radiopharmaceuticals in clinical applications of nuclear medicine.

[0083] In summary, this invention provides a method for preparing 225Ac and 212Pb by controlling and suppressing the photonuclear reaction of 210Pb impurities. By utilizing the threshold differences of different photonuclear reactions, the electron beam energy is precisely controlled within the 38-42 MeV range. 210 The Pb impurity activity decreased by 60.7% compared to the 50 MeV operating condition. 210 Pb / 212 Pb activity ratio was strictly controlled at 2×10⁻⁶. -5 Internally, it solved the problem at its source. 210 Pb and 212 The industry-wide challenge of chemically separating Pb eliminates the long-term radiation dose burden on products. 225 Ac's output retained over 94.3% 212 While maintaining a Pb yield of over 91.0%, the technology achieves radioactivity purity of ≥99.998% for both nuclides, overcoming the bottleneck of the current technology where high yield and low impurities are mutually exclusive. Impurity suppression can be achieved solely through electron beam energy parameter adjustment, eliminating the need for additional chemical separation steps. This results in low engineering implementation costs, high reproducibility, and the simultaneous preparation of two clinically urgently needed alpha emitter nuclides, significantly improving equipment utilization and effectively alleviating the shortage of medical isotopes.

[0084] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing 225Ac and 212Pb by controlling and suppressing 210Pb impurities through photonuclear reaction, characterized in that, Includes the following steps: Bremsstrahlung photon irradiation generated by an electron beam passing through a bremsstrahlung conversion target 226 Ra target, through 226 Ra(γ,n) reaction generates 225 Ra decays to 225 Ac, and through 226 Ra(γ, 2n) reaction generates 224 Ra decays to 212 Pb, for the simultaneous preparation of medical isotopes 225 Ac and 212 Pb; wherein, the electron beam energy range of the electron accelerator output is 38~42MeV, making 226 The Ra(γ,4n) reaction was inhibited, and the resulting irradiated products contained... 210 Pb activity and 212 The ratio of Pb activity ≤ 2 × 10 -5 .

2. The method for preparing 225Ac and 212Pb by photonuclear reaction with controlled suppression of 210Pb impurities according to claim 1, characterized in that, The electron beam is output by an acceleration device with a rated power of 60kW and a rated energy range of 30~50MeV. In production mode, the electron energy is locked in a preset range of 38~42MeV. The acceleration device includes an online electron energy monitoring device and an interlock protection device. When the electron energy deviates from the set value by more than ±2%, the beam is automatically cut off.

3. The method for preparing 225Ac and 212Pb photonuclear reactions with controlled suppression of 210Pb impurities according to claim 2, characterized in that, The energy stability of the electron beam is controlled within ±1%, and real-time regulation is achieved through the high-frequency voltage closed-loop feedback system of the acceleration device.

4. The method for preparing 225Ac and 212Pb photonuclear reactions with controlled suppression of 210Pb impurities according to claim 1, characterized in that, The bremsstrahlung conversion target is a tantalum target.

5. The method for preparing 225Ac and 212Pb photonuclear reactions with controlled suppression of 210Pb impurities according to claim 4, characterized in that, The longitudinal thickness of the tantalum target is 3 mm.

6. The method for preparing 225Ac and 212Pb photonuclear reactions with controlled suppression of 210Pb impurities according to claim 1, characterized in that, The 226 The Ra target charge is 1g, the electron beam power is 60kW, and the irradiation duration is 10 days.

7. The method for preparing 225Ac and 212Pb photonuclear reactions with controlled suppression of 210Pb impurities according to claim 1, characterized in that, The 226 The Ra target is covered with an aluminum cladding for physical isolation and initial sealing during the irradiation process.

8. The method for preparing 225Ac and 212Pb photonuclear reactions with controlled suppression of 210Pb impurities according to claim 1, characterized in that, Prepared 225 The radioactivity purity of Ac products is ≥99.998%.

9. The method for preparing 225Ac and 212Pb photonuclear reactions with controlled suppression of 210Pb impurities according to claim 1, characterized in that, Prepared 212 The radioactive purity of Pb products is ≥99.998%.

10. The product prepared by the method according to any one of claims 1 to 9 225 Ac and / or 212 Application of Pb in the preparation of radiopharmaceuticals for targeted alpha therapy.

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