Micro-dosimetry-based evaluation method for targeted alpha radionuclide treatment biological effective dose

Abstract

The invention provides a microdosimetry-based evaluation method for a targeted alpha radionuclide treatment biological effective dose, and the method comprises the steps: carrying out the integration of a time activity curve of alpha radionuclide in an organ, obtaining the cumulative activity, and calculating the physical absorbed dose and dose rate of the organ through Monte Carlo simulation; based on micro-dose Monte Carlo simulation, constructing a micro-dose spectrum of the alpha radionuclide to obtain saturation correction dose average linear energy for representing radiation quality; obtaining biological effect parameters of the alpha radionuclide by fitting saturation correction dose average line energy and cell experiment data by using a micro-dose kinetic model; and evaluating the biological effective dose of the target organ in combination with the physical absorbed dose, the dose rate and the biological effect parameter. According to the method, the problem that a biological effective dose evaluation method is lacked in dose evaluation of targeted alpha radionuclide treatment is solved.

Description

Technical Field

[0001] The present application relates to the technical field of targeted α-radionuclide therapy, and in particular to a method for evaluating biological effective dose of targeted α-radionuclide therapy based on microdosimetry. Background Art

[0002] Prostate-specific membrane antigen (PSMA) labeled with alpha radionuclides has achieved good results in targeted treatment of metastatic refractory prostate cancer (mCRPC). Compared with beta rays, alpha rays have a shorter range, and the alpha radionuclides accumulated in the tumor have less impact on surrounding normal tissues; the LET of alpha rays is higher than that of beta rays, and the killing effect on tumor cells is stronger; in addition, it has also been found clinically that 225 Ac-PSMA-617 can overcome patients' 177 Lu-PSMA-617 has drug resistance and hematotoxicity. Therefore, targeted α-radiotherapy has become an important research field. The radiation dose to tumors or normal tissues directly affects the effect and side effects of treatment, so dose assessment in targeted α-radionuclide therapy is crucial.

[0003] In the dose assessment of targeted α-radionuclide therapy, since the energy deposition of high-LET α particles is more dense, the physical absorbed dose is insufficient to describe the biological effect of α particles. Therefore, it is necessary to establish a method for assessing the biological effective dose of targeted α-radionuclide therapy.

[0004] However, in existing dose calculation studies of targeted α-radionuclide therapy, the relative biological effect is taken as a fixed value, or calculated according to an empirical formula, which cannot reflect the influence of factors such as cell type, radiation dose, and dose rate. In addition, the existing dose assessment methods for targeted α-radionuclide therapy fail to link the microscopic energy deposition characteristics of α particles with macroscopic biological effects, and lack a method for assessing the biological effective dose. Summary of the invention

[0005] The present application aims to solve one of the technical problems in the related art at least to some extent.

[0006] To this end, the first objective of the present application is to propose a method for evaluating the biological effective dose of targeted α-radionuclide therapy based on microdosimetry.

[0007] The second object of the present application is to propose a device for evaluating the biological effective dose of targeted α-radionuclide therapy based on microdosimetry.

[0008] The third objective of the present application is to provide an electronic device.

[0009] A fourth objective of the present application is to provide a computer-readable storage medium.

[0010] A fifth object of the present application is to provide a computer program product.

[0011] To achieve the above-mentioned purpose, the first embodiment of the present application proposes a method for evaluating the biological effective dose of targeted α-radionuclide therapy based on microdosimetry, comprising:

[0012] The time activity curve of α radionuclides in organs is integrated to obtain the cumulative activity, and the physical absorbed dose and dose rate of the organs are calculated by Monte Carlo simulation;

[0013] Based on microdose Monte Carlo simulation, the microdose spectrum of α-radionuclide is constructed to obtain the average line energy of saturation-corrected dose used to characterize radiation quality.

[0014] Using a microdose kinetic model, the biological effect parameters of α-radionuclide are obtained by fitting the saturation-corrected dose average line energy with the cell experimental data;

[0015] The biological effective dose of the target organ is evaluated by combining the physical absorbed dose, the dose rate and the biological effect parameter.

[0016] Optionally, integrating the time activity curve of α radionuclides in the target organ to obtain the cumulative activity, and calculating the physical absorbed dose and dose rate of the organ by Monte Carlo simulation, comprises:

[0017] The time activity curve of alpha radionuclides in the organ is integrated to obtain the cumulative activity;

[0018] The accumulated activity is used as a source term of Monte Carlo dose simulation to calculate the physical absorbed dose of the organ;

[0019] The dose rate is calculated by the following formula:

[0020]

[0021] in, is the dose rate of the target organ k at time t, A i (t) is the activity of the radionuclide in source organ i at time t, S i→k It is the conversion factor from unit activity in source organ i to absorbed dose in target organ k.

[0022] Optionally, the microdose spectrum of α-radionuclide is constructed based on microdose Monte Carlo simulation to obtain the saturation-corrected dose average line energy for characterizing radiation quality, including:

[0023] The decay of alpha radionuclides is simulated using Monte Carlo simulation software, recording the location and energy of all energy deposition for each incident particle;

[0024] Randomly select one of the energy depositions and count all the energy depositions in the surrounding sensitive volume, divide it by the average chord length of the sensitive volume to calculate the line energy y, and generate the microdose spectrum f(y) according to the line energy distribution;

[0025] Based on the microdose spectrum f(y), the saturation-corrected dose average line energy y is calculated * , the expression is:

[0026]

[0027] Among them, y0 is the saturation parameter, which is related to the geometric characteristics of the sensitive volume, the radius of the cell nucleus and the biological effect parameter β.

[0028] Optionally, the saturation-corrected dose average line can be combined with cell experimental data, and the biological effect parameters of α-radionuclide are obtained by fitting a microdose kinetic model, including:

[0029] The following formula is used to fit the relationship between the cell survival fraction S and the absorbed dose D:

[0030]

[0031] Among them, α and β are biological effect parameters related to cell type and radiation type, respectively;

[0032] Among them, the calculation expression of the biological effect parameter α is:

[0033]

[0034] Among them, α0 is the initial bioeffect parameter, R n is the radius of the nucleus, ρ is the density of the nucleus, r d is the average chord length of the sensitive volume.

[0035] Optionally, also include:

[0036] For the cell cluster model used for α-radionuclide microdose simulation, the simulated cell is composed of three concentric spheres with different radii, which respectively divide the cell nucleus, cytoplasm and cell membrane;

[0037] The simulated cells in the cell cluster model are evenly arranged in three-dimensional space.

[0038] Optionally, in the microdose Monte Carlo simulation, there are four settings for the decay position of the alpha radioactive nuclide, namely: uniform distribution within the cell, uniform distribution in the cytoplasm, uniform distribution in the intercellular space, and uniform distribution in the entire cell cluster model.

[0039] Optionally, the combining the physical absorbed dose, the dose rate and the biological effect parameter to evaluate the biological effective dose of the target organ includes:

[0040] The biological effective dose is calculated according to the following formula:

[0041]

[0042] Wherein, BED is the biological effective dose, G(T) is a factor describing the effect of dose rate on the radiation biological effect, and its calculation formula is:

[0043]

[0044] Among them, μ is the repair coefficient.

[0045] To achieve the above-mentioned purpose, the second embodiment of the present application proposes a device for evaluating biological effective dose of targeted α-radionuclide therapy based on microdosimetry, comprising:

[0046] The physical dose simulation module is used to integrate the time activity curve of α radionuclides in organs to obtain the cumulative activity, and calculate the physical absorbed dose and dose rate of the organs through Monte Carlo simulation;

[0047] The microdose spectrum generation module is used to construct the microdose spectrum of α radionuclides based on microdose Monte Carlo simulation, and obtain the saturation-corrected dose average line energy used to characterize the radiation quality;

[0048] A biological effect parameter fitting module is used to obtain the biological effect parameters of alpha radionuclides by fitting the saturation-corrected dose average line energy with cell experimental data using a microdose dynamics model;

[0049] The biological effective dose calculation module is used to evaluate the biological effective dose of the target organ by combining the physical absorbed dose, the dose rate and the biological effect parameter.

[0050] To achieve the above-mentioned purpose, the third aspect of the present application provides an electronic device, including: a processor, and a memory communicatively connected to the processor;

[0051] The memory stores computer-executable instructions;

[0052] The processor executes the computer-executable instructions stored in the memory to implement the method as described in any one of the first aspects.

[0053] To achieve the above-mentioned purpose, the fourth aspect embodiment of the present application proposes a computer-readable storage medium, in which computer-readable storage medium is stored computer execution instructions, and when the computer execution instructions are executed by a processor, they are used to implement the method as described in any one of the first aspects.

[0054] To achieve the above-mentioned purpose, the fifth aspect of the present application proposes a computer program product, which implements any method in the first aspect when executed by a processor.

[0055] The technical solution provided by the embodiments of the present application brings at least the following beneficial effects:

[0056] (1) This application breaks through the technical bottleneck of the lack of biological effective dose assessment methods for targeted α-radionuclide therapy in the prior art, and constructs a comprehensive assessment system that combines macro and micro scales. By combining Monte Carlo simulation at the organ level and microdose kinetic model at the cell scale, an accurate assessment method is provided, which provides a scientific basis for the optimal design and application of α-radionuclide therapy.

[0057] (2) This application uses microdose Monte Carlo simulation to establish the microdose spectrum of α particles in the cell nucleus, and fits the microdose kinetic model to accurately calculate the biological effect parameters (such as α and β parameters) of different cell types. This method effectively reflects the biological effects of α radionuclides at the cellular level, filling the technical gap that traditional physical dose assessment cannot characterize microscopic biological effects.

[0058] (3) The evaluation method of this application can fully reflect the impact of factors such as cell type, radiation dose and dose rate on the biological effective dose, and provide a more detailed and scientific dosimetric analysis. This multi-factor comprehensive analysis method significantly improves the accuracy and personalization of α-radionuclide treatment plans, laying the foundation for more efficient and safer targeted radiotherapy.

[0059] Additional aspects and advantages of the present application will be given in part in the description below, and in part will become apparent from the description below, or will be learned through the practice of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0060] The above and / or additional aspects and advantages of the present application will become apparent and easily understood from the following description of the embodiments in conjunction with the accompanying drawings, in which:

[0061] Figure 1 A schematic flow chart of a method for evaluating biological effective dose of targeted α-radionuclide therapy based on microdosimetry provided in an embodiment of the present application;

[0062] Figure 2A schematic flow chart of a method for evaluating biological effective dose of targeted α-radionuclide therapy based on microdosimetry provided in an embodiment of the present application;

[0063] Figure 3 A schematic diagram of a cell cluster model for microdose simulation provided in an embodiment of the present application;

[0064] Figure 4 A schematic diagram of the structure of a device for evaluating biological effective dose of targeted α-radionuclide therapy based on microdosimetry provided in an embodiment of the present application. DETAILED DESCRIPTION

[0065] Embodiments of the present application are described in detail below, and examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present application, and should not be construed as limiting the present application.

[0066] In existing dose calculation studies of targeted α-radionuclide therapy, the relative biological effect is taken as a fixed value or calculated according to an empirical formula, which cannot reflect the influence of factors such as cell type, radiation dose, and dose rate. In addition, the existing dose assessment methods for targeted α-radionuclide therapy fail to link the microscopic energy deposition characteristics of α particles with macroscopic biological effects, and lack a method for assessing the biological effective dose.

[0067] To address this problem, an embodiment of the present application provides a method for evaluating the biological effective dose of targeted α-radionuclide therapy based on microdosimetry, in which Monte Carlo simulation is performed at the organ level to obtain the organ absorbed dose and absorbed dose rate; at the same time, microdose simulation of α-radionuclide is performed at the cellular scale to obtain the microdose spectrum in the cell nucleus, and for different types of cells, the microdose kinetic model is fitted to obtain the biological effect parameters of different cells, thereby evaluating the biological effective dose (BED) of the organ, thereby solving the problem of the lack of an evaluation method for the biological effective dose in the dose evaluation of targeted α-radionuclide therapy.

[0068] Figure 1 and Figure 2 The present invention provides a flow chart of a method for evaluating the biological effective dose of targeted α-radionuclide therapy based on microdosimetry. Figure 1 As shown, the method comprises the following steps:

[0069] Step 101, integrating the time activity curve of α radionuclides in the organ to obtain the cumulative activity, and calculating the physical absorbed dose and dose rate of the organ through Monte Carlo simulation.

[0070] In the embodiment of the present application, the time activity curve of the α radionuclide in the organ is first integrated to obtain the cumulative activity, and then the cumulative activity is used as the source term of the Monte Carlo dose simulation to calculate the physical absorbed dose of the organ. In addition, the dose rate simulation of the target organ k is calculated by the following formula, which is expressed as:

[0071]

[0072] in, is the dose rate of the target organ k at time t, A i (t) is the activity of the radionuclide in source organ i at time t, S i→k It is the conversion factor from unit activity in source organ i to absorbed dose in target organ k.

[0073] Step 102: construct a microdose spectrum of α-radionuclide based on microdose Monte Carlo simulation to obtain the average line energy of saturation-corrected dose for characterizing radiation quality.

[0074] In the embodiment of the present application, the decay of α-radioactive nuclides is simulated using Monte Carlo simulation software, and the position and energy of all energy deposition of each incident particle are recorded.

[0075] In a possible embodiment, the microdose simulation of α rays can be performed according to the calculation program of the nanodose Monte Carlo simulation software NASIC developed by this laboratory, and the position and energy of all energy deposition of each incident particle can be recorded by adding microdose spectrum statistics in the physical module of NASIC.

[0076] Then, one of the energy depositions is randomly selected and all the energy depositions in the surrounding sensitive volume are counted, and the line energy y is calculated by dividing it by the average chord length of the sensitive volume, and the microdose spectrum f(y) is generated according to the line energy distribution.

[0077] Furthermore, based on the microdose spectrum f(y), the dose average line energy y for saturation correction is calculated * , the expression is:

[0078]

[0079] Among them, y0 is a saturation parameter, which is related to the geometric characteristics of the sensitive volume, the cell nucleus radius and the biological effect parameter β, and its expression is:

[0080]

[0081] Among them, R n is the radius of the nucleus, ρ is the density of the nucleus, r d is the average chord length of the sensitive volume.

[0082] It should be noted that the dose average line can* It reflects the influence of heavy ion radiation quality on cell survival.

[0083] In the present embodiment, a cell cluster model was constructed in NASIC, and a microdose simulation of α-radionuclide was performed. Figure 3 The model cell is composed of three concentric spheres with radii of 5.5μm, 9.9μm and 10.0μm, which respectively divide the nucleus, cytoplasm and cell membrane. In addition, the simulated cells in the cell cluster model are evenly arranged in the x, y and z directions of the three-dimensional space.

[0084] In addition, in order to explore the influence of the nuclide distribution position on the microdose distribution in the cell nucleus, in the microdose Monte Carlo simulation, there are four settings for the decay position of the α radionuclide: uniform distribution in the cell, uniform distribution in the cytoplasm, uniform distribution in the intercellular space, and uniform distribution in the entire cell cluster model. The line energy of the rays generated by each decay of the mother or daughter in the decay chain is counted separately to obtain the microdose spectrum of the entire decay chain. It is then brought into the microdose kinetic model, and the parameters of the microdose kinetic model are iteratively optimized using the least squares method based on the cell experimental data to obtain the biological effect parameters α and β of the α radionuclide.

[0085] Step 103, using the microdose kinetic model, the biological effect parameters of the α-radionuclide are obtained by fitting the saturation-corrected dose average line energy with the cell experimental data.

[0086] In the embodiments of the present application, the microdose kinetic model (MKM) used is a radiation bioeffect model based on the dual radiation action theory established by Japan NIRS, and is widely used in the biological effect evaluation of proton and heavy ion radiotherapy.

[0087] In this microdose kinetic model, the following formula is used to fit the relationship between the cell survival fraction S and the absorbed dose D, which is expressed as:

[0088]

[0089] Among them, α and β are biological effect parameters related to cell type and radiation type, respectively.

[0090] Among them, the calculation expression of the biological effect parameter α is:

[0091]

[0092] Among them, α0 is the initial bioeffect parameter, R n is the radius of the nucleus, ρ is the density of the nucleus, r d is the average chord length of the sensitive volume.

[0093] In the present embodiment, the microdose kinetic model was refitted using multiple existing sets of monoenergetic α-ray cell experimental data. The cell data were obtained from the PIDE database, including 27 sets of α-ray irradiated in vitro V79 cells (Chinese hamster cells) and 6 sets of α-ray irradiated in vitro Renca cells (mouse renal cancer cells).

[0094] Step 104, combining the physical absorbed dose, dose rate and biological effect parameters to evaluate the biological effective dose of the target organ.

[0095] In the embodiments of the present application, the biological effective dose (BED) is calculated according to the following formula, combining the results of macroscopic physical dose simulation and microscopic microdose simulation:

[0096]

[0097] Among them, BED is the biological effective dose, α and β are the biological effect parameters obtained by microdose simulation, and G(T) is a factor that describes the effect of dose rate on radiation biological effects. Its calculation formula is:

[0098]

[0099] Among them, μ is the repair coefficient.

[0100] In order to implement the above-mentioned embodiments, the present application also proposes a device for evaluating biological effective dose of targeted α-radionuclide therapy based on microdosimetry. Figure 4 The structure diagram of a device 10 for evaluating biological effective dose of targeted α-radionuclide therapy based on microdosimetry provided in an embodiment of the present application is shown in FIG. Figure 4 As shown, the device comprises:

[0101] The physical dose simulation module 100 is used to integrate the time activity curve of α radionuclides in the organ to obtain the cumulative activity, and calculate the physical absorbed dose and dose rate of the organ through Monte Carlo simulation;

[0102] The microdose spectrum generation module 200 is used to construct a microdose spectrum of α-radionuclide based on microdose Monte Carlo simulation, and obtain the saturation-corrected dose average line energy for characterizing the radiation quality;

[0103] The biological effect parameter fitting module 300 is used to obtain the biological effect parameters of α radionuclides by fitting the saturation-corrected dose average line energy and cell experimental data using a microdose dynamics model;

[0104] The biological effective dose calculation module 400 is used to evaluate the biological effective dose of the target organ by combining the physical absorbed dose, the dose rate and the biological effect parameter.

[0105] In order to implement the above embodiments, the present application also proposes an electronic device, comprising: a processor, and a memory communicatively connected to the processor; the memory stores computer-executable instructions; the processor executes the computer-executable instructions stored in the memory to implement the method provided by the above embodiments.

[0106] In order to implement the above embodiments, the present application also proposes a computer-readable storage medium, in which computer-executable instructions are stored. When the computer-executable instructions are executed by a processor, they are used to implement the methods provided by the above embodiments.

[0107] In order to implement the above embodiments, the present application also proposes a computer program product, including a computer program, which implements the methods provided by the above embodiments when executed by a processor.

[0108] The collection, storage, use, processing, transmission, provision and disclosure of user personal information involved in this application are in compliance with relevant laws and regulations and do not violate public order and good morals.

[0109] It should be noted that personal information from users should be collected for legitimate and reasonable purposes and should not be shared or sold outside of these legitimate uses. In addition, such collection / sharing should be carried out after receiving the user's informed consent, including but not limited to notifying the user to read the user agreement / user notice and sign the agreement / authorization including authorization of relevant user information before the user uses the function. In addition, any necessary steps should be taken to protect and safeguard access to such personal information data and ensure that others who have access to personal information data comply with its privacy policy and procedures.

[0110] The present application is expected to provide an implementation scheme for users to selectively block the use or access of personal information data. That is, the present disclosure is expected to provide hardware and / or software to prevent or block access to such personal information data. Once the personal information data is no longer needed, the risk can be minimized by limiting data collection and deleting the data. In addition, when applicable, such personal information is de-identified to protect the privacy of the user.

[0111] In the description of the aforementioned embodiments, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present application. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0112] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features. In the description of this application, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0113] Any process or method description in a flowchart or otherwise described herein may be understood to represent a module, fragment or portion of code comprising one or more executable instructions for implementing the steps of a custom logical function or process, and the scope of the preferred embodiments of the present application includes alternative implementations in which functions may not be performed in the order shown or discussed, including performing functions in a substantially simultaneous manner or in the reverse order depending on the functions involved, which should be understood by technicians in the technical field to which the embodiments of the present application belong.

[0114] The logic and / or steps represented in the flowchart or otherwise described herein, for example, can be considered as an ordered list of executable instructions for implementing logical functions, and can be embodied in any computer-readable medium for use by an instruction execution system, device or apparatus (such as a computer-based system, a system including a processor, or other system that can fetch instructions from an instruction execution system, device or apparatus and execute the instructions), or in combination with these instruction execution systems, devices or apparatuses. For the purpose of this specification, "computer-readable medium" can be any device that can contain, store, communicate, propagate or transmit a program for use by an instruction execution system, device or apparatus, or in combination with these instruction execution systems, devices or apparatuses. More specific examples of computer-readable media (a non-exhaustive list) include the following: an electrical connection with one or more wires (electronic device), a portable computer disk box (magnetic device), a random access memory (RAM), a read-only memory (ROM), an erasable and programmable read-only memory (EPROM or flash memory), a fiber optic device, and a portable compact disk read-only memory (CDROM). In addition, the computer-readable medium may even be paper or other suitable medium on which the program is printed, since the program may be obtained electronically, for example, by optically scanning the paper or other medium and then editing, interpreting or processing in other suitable ways if necessary, and then stored in a computer memory.

[0115] It should be understood that the various parts of the present application can be implemented by hardware, software, firmware or a combination thereof. In the above-mentioned embodiments, multiple steps or methods can be implemented by software or firmware stored in a memory and executed by a suitable instruction execution system. For example, if implemented by hardware, as in another embodiment, it can be implemented by any one of the following technologies known in the art or their combination: a discrete logic circuit having a logic gate circuit for implementing a logic function for a data signal, a dedicated integrated circuit having a suitable combination of logic gate circuits, a programmable gate array (PGA), a field programmable gate array (FPGA), etc.

[0116] A person skilled in the art may understand that all or part of the steps in the method for implementing the above-mentioned embodiment may be completed by instructing related hardware through a program, and the program may be stored in a computer-readable storage medium, which, when executed, includes one or a combination of the steps of the method embodiment.

[0117] In addition, each functional unit in each embodiment of the present application may be integrated into a processing module, or each unit may exist physically separately, or two or more units may be integrated into one module. The above-mentioned integrated module may be implemented in the form of hardware or in the form of a software functional module. If the integrated module is implemented in the form of a software functional module and sold or used as an independent product, it may also be stored in a computer-readable storage medium.

[0118] The storage medium mentioned above may be a read-only memory, a magnetic disk or an optical disk, etc. Although the embodiments of the present application have been shown and described above, it can be understood that the above embodiments are exemplary and cannot be understood as limiting the present application. A person of ordinary skill in the art may change, modify, replace and modify the above embodiments within the scope of the present application.

[0119] It should be understood that the various forms of processes shown above can be used to reorder, add or delete steps. For example, the steps recorded in this application can be executed in parallel, sequentially or in different orders, as long as the expected results of the technical solution of this application can be achieved, and this document is not limited here.

[0120] The above specific implementations do not constitute a limitation on the protection scope of this application. It should be understood by those skilled in the art that various modifications, combinations, sub-combinations and substitutions can be made according to design requirements and other factors. Any modifications, equivalent substitutions and improvements made within the spirit and principles of this application should be included in the protection scope of this application.

Claims

1. A method for evaluating biological effective dose of targeted α-radionuclide therapy based on microdosimetry, characterized in that: The following steps are involved: The time activity curve of α radionuclides in organs is integrated to obtain the cumulative activity, and the physical absorbed dose and dose rate of the organs are calculated by Monte Carlo simulation; Based on microdose Monte Carlo simulation, the microdose spectrum of α-radionuclide is constructed to obtain the average line energy of saturation-corrected dose used to characterize radiation quality. Using a microdose kinetic model, the biological effect parameters of α-radionuclide are obtained by fitting the saturation-corrected dose average line energy with the cell experimental data; The biological effective dose of the target organ is evaluated by combining the physical absorbed dose, the dose rate and the biological effect parameter.

2. The method according to claim 1, characterized in that The step of integrating the time activity curve of the α radioactive nuclide in the target organ to obtain the cumulative activity and calculating the physical absorbed dose and dose rate of the organ by Monte Carlo simulation includes: The time activity curve of alpha radionuclides in the organ is integrated to obtain the cumulative activity; The accumulated activity is used as a source term of Monte Carlo dose simulation to calculate the physical absorbed dose of the organ; The dose rate is calculated by the following formula: in, is the dose rate of the target organ k at time t, A i (t) is the activity of the radionuclide in source organ i at time t, S i→k It is the conversion factor from unit activity in source organ i to absorbed dose in target organ k.

3. The method according to claim 2, characterized in that The method of constructing a microdose spectrum of α-radionuclide based on microdose Monte Carlo simulation and obtaining a saturation-corrected dose average line energy for characterizing radiation quality includes: The decay of alpha radionuclides is simulated using Monte Carlo simulation software, recording the location and energy of all energy deposition for each incident particle; Randomly select one of the energy depositions and count all the energy depositions in the surrounding sensitive volume, divide it by the average chord length of the sensitive volume to calculate the line energy y, and generate the microdose spectrum f(y) according to the line energy distribution; Based on the microdose spectrum f(y), the saturation-corrected dose average line energy y is calculated * , the expression is: Among them, y0 is the saturation parameter, which is related to the geometric characteristics of the sensitive volume, the radius of the cell nucleus and the biological effect parameter β.

4. The method according to claim 3, characterized in that The saturation-corrected dose average line can be combined with the cell experimental data, and the biological effect parameters of the alpha radionuclide are obtained by fitting the microdose kinetic model, including: The following formula is used to fit the relationship between the cell survival fraction S and the absorbed dose D: Among them, α and β are biological effect parameters related to cell type and radiation type, respectively; Among them, the calculation expression of the biological effect parameter α is: Among them, α0 is the initial bioeffect parameter, R n is the radius of the nucleus, ρ is the density of the nucleus, r d is the average chord length of the sensitive volume.

5. The method according to claim 4, characterized in that Also includes: For the cell cluster model used for α-radionuclide microdose simulation, the simulated cell is composed of three concentric spheres with different radii, which respectively divide the cell nucleus, cytoplasm and cell membrane; The simulated cells in the cell cluster model are evenly arranged in three-dimensional space.

6. The method according to claim 5, characterized in that In the microdose Monte Carlo simulation, there are four settings for the decay positions of alpha radionuclides, namely: uniform distribution within the cell, uniform distribution in the cytoplasm, uniform distribution in the intercellular space, and uniform distribution in the entire cell cluster model.

7. The method according to claim 6, characterized in that The step of combining the physical absorbed dose, the dose rate and the biological effect parameter to evaluate the biological effective dose of the target organ comprises: The biological effective dose is calculated according to the following formula: Wherein, BED is the biological effective dose, G(T) is a factor describing the effect of dose rate on the radiation biological effect, and its calculation formula is: Among them, μ is the repair coefficient.

8. A device for evaluating biological effective dose of targeted α-radionuclide therapy based on microdosimetry, characterized in that: include: The physical dose simulation module is used to integrate the time activity curve of α radionuclides in organs to obtain the cumulative activity, and calculate the physical absorbed dose and dose rate of the organs through Monte Carlo simulation; The microdose spectrum generation module is used to construct the microdose spectrum of α radionuclides based on microdose Monte Carlo simulation, and obtain the saturation-corrected dose average line energy used to characterize the radiation quality; A biological effect parameter fitting module is used to obtain the biological effect parameters of alpha radionuclides by fitting the saturation-corrected dose average line energy with cell experimental data using a microdose dynamics model; The biological effective dose calculation module is used to evaluate the biological effective dose of the target organ by combining the physical absorbed dose, the dose rate and the biological effect parameter.

9. An electronic device, characterized in that: include: A processor, and a memory communicatively connected to the processor; The memory stores computer-executable instructions; The processor executes the computer-executable instructions stored in the memory to implement the method according to any one of claims 1 to 7.

10. A computer-readable storage medium, characterized in that: The computer-readable storage medium stores computer-executable instructions, which are used to implement the method according to any one of claims 1 to 7 when executed by a processor.

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