Method and system for quantifying relative bioavailability of irradiation dose in nuclide drug

Abstract

The invention belongs to the technical field of medical detection, and discloses a method and system for quantifying the relative bioavailability of the internal irradiation dose of a nuclide drug, and the method comprises the steps: dividing the same batch of experimental animals carrying tumors into two groups, and respectively carrying out the internal irradiation of a to-be-detected treatment nuclide drug and the external irradiation of a contrast nuclide drug, radiation damage information and / or radiation response information of the two groups of experimental animals are / is obtained, then the two groups of information are compared, dose pairing is carried out, and finally the relative bioavailability of the internal irradiation dose of the to-be-detected nuclide drug is calculated. The defects that in the prior art, the biological effect of nuclide medicine internal irradiation treatment is greatly different from that of traditional external irradiation radiotherapy, and a means for effectively quantifying the relative bioavailability of the nuclide medicine internal irradiation dose is lacked are overcome. The relative bioavailability of the irradiation dose in the nuclide medicine can be accurately quantified, and a scientific basis is provided for research, development and clinical application of targeted radiopharmaceuticals.

Description

Technical Field

[0001] This application relates to the field of medical testing technology, and more specifically, to a method and system for quantifying the relative bioavailability of radiopharmaceutical internal irradiation dose. Background Technology

[0002] Targeted radionuclide internal radiation therapy, as an emerging cancer treatment method, has made significant progress in clinical practice, especially for patients with distant or widespread metastatic tumors. Compared with traditional external beam radiotherapy, the characteristics of radionuclide internal radiation therapy, such as the type of radiation (e.g., gamma rays, electrons, alpha particles), spatial heterogeneity of radiation dose, and low and time-varying radiation dose rate, lead to significant differences in its biological effects. Therefore, quantitative correlation models between the biological effects induced by X-ray external irradiation and the absorbed radiation dose level are not applicable to radionuclide internal radiation therapy.

[0003] To address this issue, the academic community has defined concepts such as relative bioeffectiveness (RBE) and equivalent dose to describe the ratio of the dose required to induce a biological effect by different types and dose rates of ionizing radiation to the dose required to induce the same biological effect by reference X-rays. However, current research on these factors, apart from theoretical modeling, is usually based on relatively simplified in vitro cell experiments and a small number of small animal studies, providing only a general reference range and failing to achieve individualized and precise studies for different innovative radionuclide drugs.

[0004] With the continuous development of targeted radiopharmaceutical research, a diverse and competitive landscape has emerged for drugs targeting the same target but with different ligands and different nuclides (including beta and alpha nuclides, with differences in half-life). The pharmacokinetic properties of different drugs, as well as the radiation absorbed dose levels at lesions and sensitive organs, also exhibit significant differences. Current technology lacks a method and system capable of effectively quantifying the relative bioefficacy of internal radiation doses of radiopharmaceuticals. This limits the ability to accurately evaluate drug efficacy and safety in the early stages of clinical research, thus affecting drug development efficiency and success rates. It also makes it difficult to guide individualized dosing regimens based on precise quantification of biological effects in clinical practice, in order to improve treatment efficacy and minimize potential side effects.

[0005] To address the aforementioned issues, existing technologies urgently need improvement. Summary of the Invention

[0006] The purpose of this application is to provide a method and system for quantifying the relative bioavailability of internal radiation dose of radiopharmaceuticals, which can accurately quantify the relative bioavailability of internal radiation dose of radiopharmaceuticals.

[0007] In a first aspect, this application provides a method for quantifying the relative bioavailability of internal radiation dose of a radiopharmaceutical, which includes the following steps: A1. Divide the same batch of experimental animals carrying tumors into two groups. Inject the first group of experimental animals with different doses of the test therapeutic radionuclide drug, and inject the second group of experimental animals with a contrast radionuclide drug. The contrast radionuclide drug is a diagnostic radionuclide drug paired with the test therapeutic radionuclide drug or a reduced dose of the test therapeutic radionuclide drug. A2. For each experimental animal in the first group, the radiation absorbed dose of the therapeutic radionuclide drug to the target area was determined by SPECT imaging and X-ray imaging; A3. For each experimental animal in the second group, external beam radiotherapy was performed on the target area by SPECT imaging and / or X-ray imaging guided by X-rays. A4. Obtain radiation damage information and / or radiation response information for each experimental animal; A5. Compare the radiation damage information and / or radiation response information of the target area of ​​the two groups of experimental animals, and pair the radiation absorbed dose with the X-ray irradiation dose with similar radiation damage information and / or radiation response information; A6. Calculate the relative bioavailability of the internal radiation dose of the therapeutic radionuclide drug under test based on the paired radiation absorbed dose and the X-ray irradiation dose.

[0008] Secondly, this application provides a system for quantifying the relative bioavailability of radiopharmaceutical internal irradiation dose, used to implement the aforementioned method for quantifying the relative bioavailability of radiopharmaceutical internal irradiation dose; the system for quantifying the relative bioavailability of radiopharmaceutical internal irradiation dose includes a host computer and a frame, and further includes a moving bed, an X-ray irradiation system and a SPECT detection system arranged sequentially on the frame in the front-back direction; The movable bed is used to move the experimental animal between the X-ray irradiation station and the SPECT detection station. The SPECT detection system is used to perform SPECT imaging on the experimental animals; The X-ray detection system includes an X-ray source and an X-ray detector arranged opposite to each other, and a movable collimation mechanism disposed between the X-ray source and the X-ray detector; the X-ray source is capable of emitting a first X-ray for X-ray imaging and a second X-ray for external beam radiotherapy, the power of the second X-ray being greater than the power of the first X-ray; the movable collimation mechanism is capable of moving into the effective field of view of the X-ray detector to collimate and adjust the X-rays to form the X-ray beam required for external beam radiotherapy; the movable collimation mechanism can also move out of the effective field of view of the X-ray detector to avoid obstructing X-ray imaging; The host computer is used to control the operation of the moving bed, the X-ray irradiation system and the SPECT detection system to determine the internal irradiation dose of the therapeutic radionuclide drug relative to its bioavailability.

[0009] Beneficial Effects: This application provides a method and system for quantifying the relative bioefficiency of internal irradiation dose of radiopharmaceuticals. By dividing a batch of tumor-bearing experimental animals into two groups, one group receives internal irradiation with the target therapeutic radiopharmaceutical, and the other receives external irradiation with a control radiopharmaceutical. Radiation damage and / or radiation response information is obtained from both groups. The two groups are then compared and dose-matched to calculate the relative bioefficiency of the internal irradiation dose of the target therapeutic radiopharmaceutical. This method overcomes the shortcomings of existing technologies, such as the significant difference between the biological effects of internal irradiation therapy with radiopharmaceuticals and traditional external irradiation, and the lack of effective means to quantify the relative bioefficiency of internal irradiation dose of radiopharmaceuticals. This method can accurately quantify the relative bioefficiency of internal irradiation dose of radiopharmaceuticals, providing a scientific basis for the development and clinical application of targeted radiopharmaceuticals. Attached Figure Description

[0010] Figure 1 This is a schematic diagram of a system for quantifying the relative bioavailability of radiopharmaceutical internal irradiation dose, as provided in this application.

[0011] Figure 2 This is a schematic diagram of an X-ray detection system.

[0012] Figure 3 This is a schematic diagram of the moving bed.

[0013] Figure 4 This is a schematic diagram of the SPECT detection system.

[0014] Figure 5 A flowchart of a method for quantifying the relative bioavailability of radiopharmaceutical internal irradiation dose, provided in this application.

[0015] Labeling Explanation: 1. Frame; 2. Moving Bed; 201. Three-Axis Translation Mechanism; 202. Rotary Drive Mechanism; 203. Animal Bed; 204. Z-Axis Moving Mechanism; 205. X-Axis Moving Mechanism; 206. Y-Axis Moving Mechanism; 3. X-ray Detection System; 301. X-ray Source; 302. X-ray Detector; 303. Moving Collimation Mechanism; 304. Translation Mechanism; 305. Collimation Frame; 306. Projection Plate; 307. Collimator Switching System; 308. Collimator; 309. Transmission Aperture; 310. Light Transmission Aperture; 311. Mounting Bracket; 312. Wheel; 4. SPECT Detection System; 401. SPECT Probe; 402. Radial Motion Mechanism. Detailed Implementation

[0016] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of the embodiments. The components of the embodiments of this application 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 this application provided in the accompanying drawings is not intended to limit the scope of the claimed application, but merely represents selected embodiments of this application. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application.

[0017] It should be noted that similar reference numerals and letters in the following figures indicate similar items; therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures. Furthermore, in the description of this application, the terms "first," "second," etc., are used only to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0018] Please refer to Figure 5 This application discloses a method for quantifying the relative bioavailability of internal radiation dose to a radiopharmaceutical in some embodiments. The method includes the following steps: A1. Divide the same batch of experimental animals carrying tumors into two groups. Inject the first group of experimental animals with different doses of the test therapeutic radionuclide drug, and inject the second group of experimental animals with a contrast radionuclide drug. The contrast radionuclide drug is a diagnostic radionuclide drug paired with the test therapeutic radionuclide drug or a reduced dose of the test therapeutic radionuclide drug. A2. For each experimental animal in the first group, the radiation absorbed dose of the therapeutic radionuclide drug to the target area was determined by SPECT imaging and X-ray imaging; A3. For each experimental animal in the second group, external beam radiotherapy was performed on the target area by SPECT imaging and / or X-ray imaging guided by X-rays. A4. Obtain radiation damage information and / or radiation response information for each experimental animal; A5. Compare the radiation damage information and / or radiation response information of the target area of ​​the two groups of experimental animals, and pair the radiation absorbed dose with the X-ray irradiation dose with similar radiation damage information and / or radiation response information; A6. Calculate the relative bioavailability of the internal radiation dose of the therapeutic radionuclide drug under test based on the paired radiation absorbed dose and the X-ray irradiation dose.

[0019] This application provides a new approach for the precise assessment and individualized treatment of radiopharmaceuticals by directly comparing the biological effects of internal and external irradiation and quantifying their dose-response relationship. It effectively solves the problem of insufficient quantification of the relative bioeffectiveness of internal irradiation dose of radiopharmaceuticals in the prior art.

[0020] Among them, "radioactive drugs" refer to drugs containing radioactive nuclides used for diagnostic or therapeutic purposes, which produce a radiation effect on the lesion through internal irradiation.

[0021] "Internal irradiation" refers to the radiation generated by the decay of a radioactive nuclide after it enters the body, which then irradiates the surrounding tissues and cells.

[0022] "Relative bioeffectiveness (RBE)" is a ratio that measures the dose required to produce the same biological effect from different types of ionizing radiation, usually with reference X-rays as a benchmark.

[0023] SPECT imaging is a nuclear medicine imaging technique that acquires functional images by detecting the distribution of radioactive tracers in the body.

[0024] "X-ray imaging" is a diagnostic technique that uses X-rays to penetrate objects and form images, mainly used to obtain information about anatomical structures.

[0025] "Target area" usually refers to the area of ​​tumor lesions, which is the main target of radionuclide drugs or X-rays.

[0026] The operating environment for this method is typically equipped with animal experimental facilities and appropriate imaging and radiotherapy equipment (such as...). Figure 1 The quantification of the internal irradiation dose of the radiopharmaceutical relative to its bioeffectiveness was carried out in a laboratory or research institution using the system shown.

[0027] In step A1, the same batch of tumor-carrying experimental animals (e.g., mice) are divided into two groups. The first group of animals is injected with different doses of the test therapeutic radionuclide drug. For example, three dose gradients can be set: low, medium, and high doses, to observe the biological effects at different doses. The second group of animals is injected with a contrast radionuclide drug. This contrast radionuclide drug can be a diagnostic radionuclide drug paired with the test therapeutic radionuclide drug; for example, if the test therapeutic radionuclide drug is... 177 For Lu-labeled therapeutic drugs, the contrast radionuclide drug could be... 99m Tc-labeled diagnostic drugs; alternatively, the contrasting radionuclide can be a reduced dose of the therapeutic radionuclide being tested. For example, compared to the injection dose in the first group of experimental animals, the second group of experimental animals is injected with a lower dose (e.g., reduced to 1 / 10) of the same therapeutic radionuclide. This grouping and drug injection method can provide a control basis for subsequent internal and external irradiation experiments.

[0028] In step A2, for each experimental animal in the first group, the radiation absorbed dose of the therapeutic radionuclide drug at the target area is determined using SPECT imaging and X-ray imaging. Specifically, after injection of the radionuclide drug, SPECT imaging can be performed periodically on the experimental animals to track the distribution and clearance of the radionuclide drug in the body. Simultaneously, X-ray imaging is used to obtain anatomical location information of the target area. Using this image data, the radiation dose absorbed by the target area throughout the entire treatment cycle can be calculated using the dose estimation model recommended by the MIRD (Medical Internal Radiation Dose) committee.

[0029] In step A3, for each experimental animal in the second group, external beam radiotherapy is performed on the target area using SPECT imaging and / or X-ray imaging. Before external beam radiotherapy, SPECT imaging and / or X-ray imaging can be performed on the experimental animals to accurately determine the three-dimensional location of the target area. Based on this imaging information, the radiotherapy planning system can design multi-angle conformal intensity-modulated irradiation schemes, determining the X-ray beam size and intensity at different irradiation angles, thereby achieving precise external beam radiotherapy to the target area while maximizing the protection of surrounding normal tissues.

[0030] In step A4, radiation damage information and / or radiation response information for each experimental animal is obtained. Radiation damage information may include changes in tumor volume, such as calculating volume by periodically measuring the long and short diameters of the tumor; changes in body weight, recorded through daily or weekly weighing; complete blood count indicators, such as white blood cell, red blood cell, and platelet counts; and histopathological examination results, such as observing cell necrosis and apoptosis by staining tumor tissue sections after the experiment. Radiation response information may include the degree of tumor remission, such as assessing changes in tumor size according to RECIST criteria; and the time to disease progression, i.e., the time from the start of treatment to tumor progression.

[0031] In step A5, the radiation damage information and / or radiation response information of the target areas of the two groups of experimental animals are compared, and the radiation absorbed dose with similar radiation damage information and / or radiation response information is paired with the X-ray irradiation dose. For example, the acquired radiation damage information and / or radiation response information can be normalized to form a biological effect data set. Then, the Euclidean distance between the biological effect data sets of the first and second groups of experimental animals is calculated and compared with a preset distance threshold. If the Euclidean distance is less than the threshold, the biological effects of the two experimental animals are considered similar, and thus the radiation absorbed dose of the first group of experimental animals is paired with the X-ray irradiation dose of the second group of experimental animals.

[0032] In step A6, the relative bioefficacy (RBE) of the internal radiation dose of the therapeutic radionuclide drug under test is calculated based on the paired absorbed radiation dose and X-ray irradiation dose. For each paired absorbed radiation dose and X-ray irradiation dose, the quotient of the X-ray irradiation dose and the absorbed radiation dose can be calculated to obtain the preliminary RBE. For example, if the absorbed radiation dose of a certain experimental animal in the first group is D_internal, and its biological effect is similar to that produced by the X-ray irradiation dose D_external of a certain experimental animal in the second group, then the preliminary RBE = D_external / D_internal. Finally, by combining the preliminary RBEs obtained from all pairs, their average or weighted average can be calculated to obtain the relative bioefficacy of the internal radiation dose of the therapeutic radionuclide drug under test.

[0033] The method for quantifying the relative bioefficacy of internal radiation dose of radiopharmaceuticals proposed in this application involves dividing tumor-bearing experimental animals into an internal radiation group and an external radiation group, and administering the target therapeutic radiopharmaceutical and external X-ray radiation respectively. Using SPECT and X-ray imaging techniques, the radiation absorbed dose of the target area in the internal radiation group is precisely determined, guiding the external radiation group to undergo precise X-ray radiotherapy. Subsequently, radiation damage information and / or radiation response information of the two groups of experimental animals are acquired and compared, and the internal radiation absorbed dose with similar biological effects is paired with the external X-ray radiation dose. Finally, the relative bioefficacy of the target therapeutic radiopharmaceutical is calculated based on these paired data.

[0034] The core innovation of this method lies in providing a direct and quantitative way to compare the biological effects of internal and external X-ray irradiation of radiopharmaceuticals, thus overcoming the limitations of traditional methods in assessing the biological effects of internal irradiation. Compared to existing technologies that mainly rely on theoretical modeling or simplified in vitro experiments to estimate RBE, the method in this application, through direct comparison of internal and external irradiation in live animal models, can more realistically and accurately reflect the actual biological effects of radiopharmaceuticals in complex biological environments. For example, traditional methods may not fully consider the impact of pharmacokinetics of radiopharmaceuticals in vivo, changes in radiation dose rate over time, and differences in radiation types (such as alpha and beta particles) on biological effects. This application, by directly measuring the absorbed radiation dose of internal irradiation and the X-ray dose of external irradiation and pairing them based on actual biological effects, can more comprehensively capture the influence of these complex factors. Therefore, the method in this application can provide more reliable biological effect assessment data for the development of novel radiopharmaceuticals, help optimize drug dosage regimens, improve treatment efficacy and safety, and provide a scientific basis for personalized precision clinical treatment.

[0035] In some implementations, step A2 includes: A201. SPECT and X-ray imaging were performed on the experimental animals in the first group to obtain the first SPECT image and the first X-ray image; A202. Identify the target region based on the first SPECT image and the first X-ray image; A203. Based on the first SPECT image, the radiation absorbed dose of the therapeutic radionuclide drug to the target area is calculated using a dose estimation model.

[0036] SPECT (Single Photon Emission Tomography) imaging is used to acquire three-dimensional information on the distribution of radionuclides within experimental animals, thereby reflecting the accumulation of therapeutic radiopharmaceuticals within the target area. X-ray imaging provides anatomical information about the experimental animals, such as the location and size of tumors, to facilitate subsequent image registration and target area identification. These two imaging methods provide complementary image data, laying the foundation for accurate dose calculation.

[0037] Specifically, after obtaining the first SPECT image and the first X-ray image, image registration technology can be used to fuse the two images, thereby accurately locating and identifying the target area in the fused image. The target area typically refers to tumor tissue or a specific organ region where radiation dose needs to be assessed. The identification process can be carried out using a combination of specialized image processing software and manual interpretation to ensure accuracy.

[0038] The dose estimation model is a mathematical model used to convert the radioactivity distribution reflected in a SPECT image into absorbed dose. These models are typically based on Monte Carlo simulations or MIRD (Medical Internal Radiation Dose) methods, taking into account factors such as the decay characteristics of the nuclide, tissue density, and geometry. By inputting the radioactivity information of the target area in the first SPECT image into the dose estimation model, the radiation energy absorbed by the target area over a certain period of time, i.e., the absorbed radiation dose, can be calculated.

[0039] The proposed solution refines step A2 into steps A201, A202, and A203, making the determination of internal radiation dose more precise and systematic. First, the SPECT and X-ray images acquired in A201 provide information on nuclide distribution and anatomical structure, respectively, which are fundamental for accurate dose assessment. Second, A202 utilizes this image data to accurately identify the target area, ensuring the regional accuracy of subsequent dose calculations. Finally, A203 applies a mature dose estimation model to convert the activity information in the images into the actual absorbed radiation dose, thereby quantifying the internal radiation dose. This step-by-step refinement method ensures that each step from image acquisition to final dose calculation has a clear basis and operational procedure, significantly improving the reliability of dose assessment.

[0040] The above technical solution provides a more detailed and operable process for determining internal radiation dose, avoiding the potential ambiguity of directly determining the absorbed radiation dose in step A2. Specifically, by explicitly combining SPECT and X-ray imaging, and applying image recognition and dose estimation models, the calculation process for absorbed radiation dose becomes more standardized and repeatable. This improves the accuracy and reliability of internal radiation dose assessment, providing a solid data foundation for subsequent quantification of relative bioeffectiveness, thereby enhancing the scientific validity and persuasiveness of the entire quantification method.

[0041] In some implementations, step A3 includes: A301. Perform SPECT imaging and / or X-ray imaging on the experimental animals in the second group to obtain a second SPECT image and / or a second X-ray image; A302. Determine the three-dimensional location of the target area based on the second SPECT image and / or the second X-ray image; A303. Based on the three-dimensional position of the target area and the required X-ray irradiation dose, determine the X-ray beam size and intensity at multiple different irradiation angles for the target area; A304. Based on the three-dimensional position of the target area and the determined X-ray beam size and intensity at multiple different irradiation angles, perform multi-angle conformal intensity-modulated irradiation on the target area.

[0042] Specifically, in step A301, SPECT imaging and / or X-ray imaging are performed on the experimental animals in the second group to obtain imaging information of the target area and its surrounding tissues. SPECT imaging provides functional information about the target area, such as the distribution of radionuclides, while X-ray imaging provides high-resolution anatomical information for accurately identifying the morphology and location of the target area. Combining these two imaging methods yields more comprehensive and accurate imaging data.

[0043] Furthermore, in step A302, based on the obtained second SPECT image and / or second X-ray image, the three-dimensional location of the target area can be accurately identified and determined. This is typically done using specialized image processing software, allowing operators to delineate the precise boundaries of the tumor based on its morphology, density, or radionuclide aggregation in the image, and calculate its spatial coordinates, providing spatial positioning information for subsequent precise radiotherapy.

[0044] In step A303, based on the determined three-dimensional location of the target area and the preset X-ray irradiation dose requirements, it is necessary to determine the size and intensity of the X-ray beam at multiple different irradiation angles for the target area. This typically involves the calculation and optimization of a radiotherapy planning system, which designs the optimal irradiation scheme based on the shape and size of the target area and the location of surrounding sensitive organs to ensure that the target area receives a sufficient dose while minimizing damage to surrounding normal tissues.

[0045] Finally, in step A304, based on the X-ray beam size and intensity at multiple different irradiation angles determined in step A303, multi-angle conformal intensity-modulated irradiation is performed on the target area. Multi-angle conformal intensity-modulated irradiation is an advanced radiotherapy technique that uses X-ray beams with adjustable shape and intensity emitted from multiple angles to precisely "conform" the high-dose area to the tumor target area, while the surrounding normal tissue receives a lower irradiation dose.

[0046] The solution presented in this application overcomes the limitations of traditional simple guided irradiation by introducing a refined external beam radiotherapy process in step A3. Specifically, step A301 acquires a second SPECT image and / or a second X-ray image, providing fundamental imaging information for subsequent precise radiotherapy. Based on this imaging information, the three-dimensional location of the target area can be accurately determined in step A302, which is a prerequisite for achieving precise radiotherapy. Further, in step A303, based on the determined three-dimensional location of the target area and the expected X-ray dose, the size and intensity of the X-ray beam at multiple different irradiation angles targeting the target area can be precisely determined. This multi-angle, variable-size, and variable-intensity X-ray beam design allows the radiotherapy plan to be highly adaptable to the complex shape of the tumor. Finally, in step A304, these optimized parameters are used to perform multi-angle conformal intensity-modulated irradiation of the target area, ensuring that the X-ray dose is highly concentrated in the tumor region while minimizing radiation damage to surrounding healthy tissues.

[0047] Through the above technical solution, this application can significantly improve the accuracy and targeting of external beam radiotherapy in the second group of experimental animals. Compared with simple guided X-ray irradiation, multi-angle conformal intensity-modulated irradiation can more accurately deliver the radiation dose to the target area, effectively avoiding excessive irradiation of surrounding normal tissues, thereby reducing side effects and improving the tolerance of experimental animals. This precise dose delivery ensures the uniformity and repeatability of the external beam radiotherapy effect, making the correspondence between biological effects and external beam doses more accurate and reliable when subsequently paired with internal beam doses, thus improving the accuracy and reliability of the quantification results of the relative bioavailability of radiopharmaceutical internal beam doses.

[0048] In some preferred embodiments, the specific implementation is as follows: First, the second group of experimental animals is placed in a SPECT / X-ray integrated imaging device (e.g., Figure 1 In the illustrated radionuclide internal irradiation dose-to-bioefficiency quantification system, SPECT and X-ray imaging are performed to obtain a second SPECT image and a second X-ray image of the target area (e.g., a tumor in a mouse). Subsequently, using image processing software, combining the functional information provided by the second SPECT image and the anatomical information provided by the second X-ray image, the three-dimensional contour of the tumor is precisely delineated, and its three-dimensional location within the experimental animal is determined. Next, based on this three-dimensional location information and a preset X-ray irradiation dose (e.g., multiple gradient doses are set to simulate different internal irradiation dose levels), a multi-angle conformal intensity-modulated radiotherapy (IMRT) plan is generated through calculation and optimization using a specialized treatment planning system (TPS). This plan specifies in detail the shape, size, intensity, and irradiation time of the X-ray beam at each irradiation angle to ensure that the tumor region receives uniform and high-dose irradiation while maximizing the protection of surrounding normal tissues. Finally, according to this radiotherapy plan, the irradiation equipment (e.g., Figure 1 The X-ray source 301 and the moving collimation mechanism 303 of the X-ray detection system 3 in the radionuclide internal irradiation dose relative to bioeffectiveness quantification system shown) provide precise multi-angle conformal intensity-modulated irradiation of the target area of ​​the experimental animal (for example, five or more different irradiation angles can be set, and the X-ray beam at each angle is precisely shaped and intensity-adjusted by the projection plate 306 and collimator switching system 307 of the moving collimation mechanism 303 to achieve precise targeting of the tumor).

[0049] Specifically, the radiation damage information may include at least one of the following: changes in tumor volume, changes in body weight, blood routine indicators, and histopathological examination results.

[0050] Tumor volume changes refer to the assessment of changes in tumor size over time in experimental animals through imaging examinations (such as CT, MRI, or ultrasound) or direct measurement. The purpose is to reflect the inhibitory effect of radionuclide drugs or X-ray irradiation on tumor growth. Weight changes refer to monitoring weight fluctuations in experimental animals before and after treatment. The purpose is to assess the impact of the treatment regimen on the overall health and nutritional status of the experimental animals. Complete blood count indicators, including white blood cell count, red blood cell count, and platelet count, are used to assess systemic radiation damage in experimental animals, such as bone marrow suppression and immune function. Histopathological examination results refer to the observation of pathological changes such as cell morphology, tissue structure, degree of necrosis, and fibrosis through biopsy or necropsy of the target area or related tissues, followed by pathological section analysis. The purpose is to directly assess the degree and type of radiation damage to tissue cells.

[0051] Through the above technical solution, this application can ensure that the obtained radiation damage information has high accuracy and comprehensiveness, thereby making the quantitative results of the relative bioeffectiveness of internal radiation dose of radiopharmaceuticals more reliable and clinically instructive. Specifically, by comprehensively considering changes in tumor volume, weight, blood routine indicators, and histopathological examination results, the damage effect of radiation on organisms can be assessed from different dimensions, avoiding the limitations of a single indicator and improving the accuracy and scientific nature of the assessment.

[0052] Furthermore, the radiation response information may include at least one of the following: the degree of tumor remission and the time of disease progression.

[0053] Tumor remission refers to changes in tumor volume or lesion size after treatment. This can be assessed using standards such as RECIST (Responsive Clinical Trial of Solid Tumors), aiming to quantify the inhibitory effect of treatment on tumor growth. Time to disease progression refers to the time from the start of treatment to objective disease progression or death, aiming to evaluate the long-term effectiveness of treatment. In practice, this information can be obtained through regular imaging examinations (such as CT, MRI, PET, etc.) or clinical observation of laboratory animals.

[0054] The above technical solutions ensure that the acquired radiation response information has high clinical relevance and biological significance, improving the accuracy and reliability of the quantification results of the relative bioefficacy of internal radiation dose. Clearly defined radiation response indicators help standardize experimental procedures, reduce subjectivity in assessment, and thus make comparisons between different experimental groups more objective and scientific, providing stronger data support for the preclinical evaluation and translational research of radiopharmaceuticals.

[0055] In some implementations, step A5 includes: A501. After normalizing the radiation damage information and / or radiation response information of the target area of ​​each experimental animal, a biological effect data set is formed. A502. Calculate the Euclidean distance between the biological effect data sets of each experimental animal in the first group and each experimental animal in the second group; A503. Compare the Euclidean distance with a preset distance threshold to determine whether the radiation damage information and / or radiation response information of the two experimental animals are similar, and determine that the two experimental animals with similar radiation damage information and / or radiation response information are paired experimental animals; A504. Pair the radiation absorbed dose of the experimental animals belonging to the first group with the X-ray irradiation dose of the experimental animals belonging to the second group.

[0056] The "radiation damage information and / or radiation response information" can include various biological indicators such as changes in tumor volume, weight changes, blood routine indicators, histopathological examination results, tumor remission degree, and disease progression time. Because these indicators may have significantly different dimensions and numerical ranges, direct comparisons may amplify or diminish the impact of some indicators. Therefore, "normalization" refers to converting these biological indicators with different dimensions and ranges to a uniform scale, such as through methods like min-max normalization or Z-score normalization, to eliminate the influence of dimensions and ensure that all indicators have equal importance when compared. After normalization, the data is organized into a "biological effect data set" for each experimental animal, representing the comprehensive biological effects of radiation exposure on that animal.

[0057] Furthermore, "Euclidean distance" is a commonly used distance metric to measure the straight-line distance between two points in a multidimensional space. In this application, the biological effect data set of each experimental animal can be considered as a point in a multidimensional space, with each dimension corresponding to a different normalized biological indicator. By calculating the Euclidean distance between the biological effect data sets of each experimental animal in the first group (receiving internal irradiation with the tested radionuclide drug) and the biological effect data sets of each experimental animal in the second group (receiving external X-ray irradiation), the degree of similarity or difference in their biological effects can be quantitatively assessed. The smaller the Euclidean distance, the more similar the biological effects of the two experimental animals are.

[0058] In practical applications, the "preset distance threshold" is a pre-defined value used to define the degree of "similarity" in biological effects. When the calculated Euclidean distance is less than or equal to this preset distance threshold, the radiation damage information and / or radiation response information of the two experimental animals are considered similar, thus identifying them as "paired experimental animals." This threshold can be set based on previous experimental data, statistical analysis, or clinical experience to ensure the rationality and effectiveness of the pairing. Therefore, once paired experimental animals are identified, the "radiation absorbed dose" of the therapeutic radionuclide drug received by the first group of experimental animals can be correlated with the "X-ray irradiation dose" received by the second group of experimental animals. This pairing is based on the similar biological effects produced by both animals, thus providing a direct correspondence for subsequent calculations of the relative bioeffectiveness of internal radiation doses.

[0059] This application's solution effectively addresses the ambiguity and subjectivity inherent in traditional methods for determining the "similarity" of radiation damage and / or radiation response information by introducing a systematic quantitative comparison process. Specifically, firstly, by normalizing different types of biological effect data, differences in data dimensions and ranges are eliminated, ensuring fairness in the comparison of all indicators. Secondly, using Euclidean distance as a quantitative indicator, the degree of difference in biological effects between different experimental animals is accurately calculated, transforming qualitative judgment into quantitative analysis. Finally, by setting a preset distance threshold, an objective standard is provided for the definition of "similarity," avoiding bias from human judgment. It is precisely due to the synergistic effect of these steps that the pairing process between absorbed radiation dose and X-ray irradiation dose becomes more scientific and rigorous, thus laying a solid foundation for the accurate calculation of the relative bioeffectiveness of subsequent internal radiation dose.

[0060] Through the above technical solutions, this application significantly improves the objectivity, accuracy, and repeatability of dose pairing in the quantification of the relative bioefficacy of radiopharmaceutical internal radiation doses. Compared to traditional methods that rely on subjective experience to judge "similarity," this application provides a standardized and quantifiable pairing mechanism through data normalization, Euclidean distance calculation, and threshold judgment, effectively avoiding the influence of human factors on the results and ensuring the stability and reliability of experimental results. This has important practical significance for accurately evaluating the therapeutic effects of radiopharmaceuticals and guiding clinical applications.

[0061] Preferably, step A504 may include: The experimental animals belonging to the first group and the second group in the paired experimental animals were respectively designated as the first paired animal and the second paired animal. If the same first-paired animal successfully pairs with only one second-paired animal, then the radiation absorbed dose and the X-ray irradiation dose of the corresponding two experimental animals are paired. If the same first paired animal is successfully paired with multiple second paired animals, the weighting coefficient of each second paired animal is determined based on the Euclidean distance between the biological effect data sets of the same first paired animal and each second paired animal, and the weighted average of the X-ray irradiation dose of each second paired animal is calculated based on the weighting coefficient. The radiation absorbed dose of the same first paired animal is then paired with the weighted average.

[0062] Specifically, the first paired animal refers to the experimental animal belonging to the first group of paired experimental animals, which received internal irradiation with the therapeutic radionuclide drug to be tested. The second paired animal refers to the experimental animal belonging to the second group of paired experimental animals, which received external X-ray irradiation. When a first paired animal is considered successfully paired with only one second paired animal in terms of radiation damage and / or radiation response information, their respective radiation absorbed dose and X-ray irradiation dose will be directly paired. In practical applications, when the same first paired animal has similar radiation damage and / or radiation response information with multiple second paired animals, to obtain more accurate pairing results, it is necessary to determine the weighting coefficient based on the Euclidean distance between the biological effect data sets of the first paired animal and each second paired animal. For example, the smaller the Euclidean distance, the more similar the biological effects, and the corresponding second paired animal should have a larger weight when calculating the weighted average. The weighting coefficient can be inversely proportional to the Euclidean distance, or it can be converted using other mathematical functions (such as the Gaussian function). In this way, a weighted average of the X-ray irradiation dose for each of the second paired animals can be calculated and paired with the radiation absorbed dose of the first paired animal to obtain a more representative and accurate X-ray irradiation dose.

[0063] This application's solution effectively addresses the pairing ambiguity problem that may arise in traditional methods with complex biological effect data by introducing a mechanism for handling multiple pairings. Specifically, when a first paired animal exhibits similar biological effects with multiple second paired animals, instead of simply selecting one for pairing, the Euclidean distance between biological effect data groups is used to quantify the degree of similarity. The smaller the Euclidean distance, the closer the biological effects, and therefore, the X-ray irradiation dose of the second paired animal is given a higher weight in the weighted average calculation. Through this weighted average method, the dose information of all similar second paired animals can be comprehensively considered, making the final paired X-ray irradiation dose more accurately reflect the external dose level that matches the biological effects of the first paired animal. Thus, this solution can more precisely capture the biological equivalence relationship between internal and external irradiation, providing a more reliable data foundation for subsequent calculations of the relative bioeffectiveness of internal irradiation dose.

[0064] Through the above technical solution, this application can effectively avoid errors caused by simple selection or random pairing in multiple pairing scenarios, significantly improving the accuracy and reliability of pairing radiation absorbed dose with X-ray irradiation dose. This weighted average pairing strategy enables the final dose pairing results to more comprehensively and accurately reflect the similarity of biological effects, thus providing more solid data support for the quantification of the relative bioeffectiveness of radiopharmaceutical internal irradiation dose, and further enhancing the accuracy and scientific rigor of the entire quantification method.

[0065] In some implementations, step A6 includes: A601. For each pair of radiation absorbed dose and X-ray irradiation dose, calculate the quotient of the radiation absorbed dose and the X-ray irradiation dose to obtain the preliminary internal irradiation dose relative bioavailability. A602. By combining the relative bioavailability of each preliminary internal irradiation dose, the relative bioavailability of the internal irradiation dose of the therapeutic radionuclide drug to be tested is calculated.

[0066] In step A601, "calculating the quotient of the absorbed radiation dose and the X-ray irradiation dose" means dividing the absorbed radiation dose from the internal irradiation by the X-ray irradiation dose from the external irradiation. This quotient represents the ratio of the dose required for internal irradiation to that required for external irradiation to produce similar biological effects; that is, the relative bioavailability of the initial internal irradiation dose for that specific pair. For example, if an experimental animal receives a 5 Gy internal irradiation dose in its target area and produces similar radiation damage and / or radiation response information as an experimental animal that received a 10 Gy external irradiation, then the relative bioavailability of the initial internal irradiation dose for that pair is 5 / 10 = 0.5.

[0067] Furthermore, in step A602, "synthesizing the relative bioefficiencies of each preliminary internal radiation dose" can be understood as performing statistical processing on all the relative bioefficiencies of the preliminary internal radiation doses obtained through step A601 to obtain a more representative final value. The purpose is to eliminate or reduce the randomness or error that may exist in a single paired result, thereby obtaining a more stable and reliable relative bioefficiency of the internal radiation dose of the therapeutic radionuclide drug under test. The synthesis method can be calculating the average or weighted average of the relative bioefficiencies of each preliminary internal radiation dose.

[0068] The proposed method decomposes the complex overall quantification problem into multiple independently assessable sub-problems by first calculating the preliminary internal radiation dose relative bioefficacy for each effective dose pair. This step-by-step calculation allows for a clear quantification of the dose-effect relationship for each pair. Based on this, by comprehensively processing these preliminary internal radiation dose relative bioefficacy results—for example, using averages, weighted averages, or other statistical methods—random fluctuations and individual differences in the experimental data can be effectively smoothed, thus avoiding biases that might arise from a single pair result. This comprehensive processing mechanism ensures that the final calculated internal radiation dose relative bioefficacy of the tested radionuclide drug more comprehensively and accurately reflects the true biological effect of the radionuclide drug, improving the robustness and reliability of the quantification results.

[0069] By employing the aforementioned technical solution, this application overcomes the problem of insufficient representativeness of single-pair results that may exist in traditional methods. By calculating and comprehensively processing multiple preliminary internal radiation dose relative bioefficiencies, the impact of experimental errors and individual differences on the final results can be effectively reduced, thereby obtaining more accurate, stable, and statistically significant internal radiation dose relative bioefficiencies of the tested radionuclide drug. This has important guiding significance for the preclinical evaluation, dosimetry optimization, and new drug development of radionuclide drugs, and can provide more reliable data support for precision treatment with radionuclide drugs.

[0070] Please refer to Figures 1-4 This application also provides a system for quantifying the relative bioefficacy of internal radiation dose of radiopharmaceuticals, used to implement the aforementioned method for quantifying the relative bioefficacy of internal radiation dose of radiopharmaceuticals; the system includes a host computer and a rack 1, and further includes components along the front-back direction (e.g., ...). Figure 1 In the diagram, the front-back direction refers to the X-axis direction, the left-right direction refers to the Y-axis direction, and the up-down direction refers to the Z-axis direction. The moving bed 2, X-ray detection system 3, and SPECT detection system 4 are sequentially arranged on the frame 1. The movable bed 2 is used to move the experimental animals between the X-ray irradiation system 3 and the SPECT detection system 4. SPECT detection system 4 is used for SPECT imaging of laboratory animals; The X-ray detection system 3 includes an X-ray source 301 and an X-ray detector 302 arranged opposite to each other, and a movable collimation mechanism 303 disposed between the X-ray source 301 and the X-ray detector 302. The X-ray source 301 is capable of emitting a first X-ray for X-ray imaging and a second X-ray for external beam radiotherapy, wherein the power of the second X-ray is greater than that of the first X-ray. The movable collimation mechanism 303 can be moved into the effective field of view of the X-ray detector 302 to collimate and adjust the X-ray (generally for the second X-ray) to form the X-ray beam required for external beam radiotherapy. The movable collimation mechanism 303 can also be moved out of the effective field of view of the X-ray detector 302 to avoid obstructing X-ray imaging. The host computer is used to control the operation of the moving bed 2, the X-ray irradiation system 3 and the SPECT detection system 4 to determine the relative bioefficacy of the internal irradiation dose of the therapeutic radionuclide drug (the specific process can be referred to the quantification method of the relative bioefficacy of the internal irradiation dose of the radionuclide drug mentioned above).

[0071] This application integrates an X-ray detection system 3 and a SPECT detection system 4, and coordinates them with a host computer to achieve X-ray imaging, SPECT imaging, and precise external irradiation radiotherapy for experimental animals. This enables accurate quantification of the relative bioeffectiveness of internal irradiation doses of radionuclide drugs, providing precise data support for new drug development and individualized clinical treatment.

[0072] The host computer serves as the control center of the entire system, coordinating the operation of each component and performing data processing and analysis. The frame 1 is the physical support structure of the system, used to fix the mobile bed 2, X-ray detection system 3, and SPECT detection system 4. The mobile bed 2 carries the experimental animals and allows for precise switching of their positions between different functional modules. The X-ray detection system 3 integrates X-ray imaging and external beam radiotherapy functions, capable of emitting X-rays of varying powers and using a moving collimation mechanism 303 to precisely shape the X-ray beam. The SPECT detection system 4 is used for single-photon emission computed tomography (SPECT) imaging of the experimental animals to obtain information on the distribution of radionuclide drugs within the body.

[0073] The core of the radiopharmaceutical internal irradiation dose relative bioeffectiveness quantification system in this application lies in achieving precise switching and coordinated operation of experimental animals under different imaging and treatment modes.

[0074] Specifically, the movable bed 2 is a key component for carrying the experimental animals. Its main function is to move the animals between the X-ray detection system 3 and the SPECT detection system 4. One implementation method is to use an electric sliding rail mechanism, driven by a stepper motor or servo motor, to achieve precise translation of the experimental animals in the forward and backward direction. For example, when X-ray imaging or external beam radiotherapy is required, the movable bed 2 moves the experimental animal to the X-ray detection system 3; when SPECT imaging is required, the movable bed 2 moves the experimental animal to the SPECT detection system 4. This switching method ensures accurate positioning of the experimental animals under different imaging and treatment modes.

[0075] The SPECT detection system 4 is used for SPECT imaging of laboratory animals. In one implementation, the SPECT detection system 4 can consist of one or more SPECT probes 401 that can rotate and scan around the laboratory animal to acquire gamma-ray data from different angles. The data is then processed by data acquisition and reconstruction algorithms to generate a three-dimensional distribution image of the nuclear drug within the laboratory animal.

[0076] The X-ray detection system 3 is another core component of this application, and its functions include X-ray imaging and external beam radiotherapy. As one implementation, the X-ray source 301 can employ a bifocal X-ray tube, achieving the emission of a first X-ray and a second X-ray by switching different focal sizes and tube voltages. For example, during X-ray imaging, the X-ray source 301 emits a lower-power first X-ray to obtain high-resolution images of anatomical structures; during external beam radiotherapy, the X-ray source 301 emits a higher-power second X-ray to provide a sufficient therapeutic dose.

[0077] The movable collimation mechanism 303 is a key component of the X-ray detection system 3, used to collimate and adjust X-rays to form the X-ray beam required for external beam radiotherapy. As one implementation, the movable collimation mechanism 303 can be composed of a multi-leaf collimator, with the opening and closing of the leaves controlled by a drive mechanism to form X-ray beams of different shapes and sizes. The movable collimation mechanism 303 can move into the effective field of view of the X-ray detector 302 to collimate and adjust the X-rays to form the X-ray beam required for external beam radiotherapy. For example, when precise irradiation of the target area for external beam radiotherapy is required, the movable collimation mechanism 303 moves into the effective field of view of the X-ray detector 302 and adjusts the leaf position according to instructions from the host computer to form an X-ray beam matching the shape of the target area. Furthermore, the movable collimation mechanism 303 can also move out of the effective field of view of the X-ray detector to avoid obstructing X-ray imaging. For example, during X-ray imaging, the movable collimation mechanism 303 can be completely moved out of the X-ray beam path to ensure that the X-ray detector 302 can receive complete X-ray image information and avoid artifacts or obstruction of the image caused by the movable collimation mechanism 303.

[0078] The host computer serves as the control center of the entire system, coordinating the operation of the moving bed 2, X-ray detection system 3, and SPECT detection system 4 to determine the relative bioefficacy of the internal radiation dose of the therapeutic radionuclide drug. As one implementation, the host computer can be a high-performance computer running specially developed control software. This software integrates modules such as image processing, dose calculation, motion control, and data analysis. For example, the host computer can receive image data acquired by the SPECT detection system 4 and the X-ray detection system 3, perform image registration and fusion, and identify the target area. Subsequently, according to the preset experimental protocol, the host computer controls the moving bed 2 to switch the experimental animal between different positions, controls the X-ray detection system 3 to perform X-ray imaging or external radiation therapy, and controls the SPECT detection system 4 to perform SPECT imaging. Finally, based on all the acquired data, combined with the dose estimation model and the biological effect model, the host computer calculates the relative bioefficacy of the internal radiation dose of the therapeutic radionuclide drug.

[0079] This application presents a system for quantifying the relative bioefficacy of radionuclide internal irradiation dose, aiming to address the shortcomings in existing technologies for quantifying the relative bioefficacy of radionuclide internal irradiation dose. Traditional methods often rely on simplified in vitro cell experiments and small-scale small animal studies, making it difficult to provide individualized and precise data for different innovative radionuclide drugs. This application integrates an X-ray detection system 3 and a SPECT detection system 4, with coordinated control by a host computer, to achieve X-ray imaging, SPECT imaging, and precise external irradiation radiotherapy for experimental animals. Compared with existing technologies, the innovations of this application are: First, the system can simultaneously perform high-resolution X-ray imaging and functional SPECT imaging. Through image fusion technology, it achieves precise identification and three-dimensional localization of the target area within the experimental animal, providing a solid foundation for subsequent precise external irradiation radiotherapy. Second, the X-ray detection system 3 integrates X-ray emission functions of different powers and a moving collimation mechanism 303, enabling the system to perform both X-ray imaging and high-precision external irradiation radiotherapy. Furthermore, the X-ray beam for external irradiation radiotherapy can be precisely adjusted according to the shape and size of the target area, ensuring the accuracy of treatment. Furthermore, the host computer, as the control core of the entire system, can coordinate the collaborative work of the moving bed 2, X-ray irradiation system 3, and SPECT detection system 4, enabling seamless switching of experimental animals between different functional modules and automating the control and data management of the entire experimental process. Therefore, this application can accurately quantify the relative bioavailability of internal irradiation doses of radiopharmaceuticals, providing more accurate pharmacodynamic and safety evaluation data for new drug development, and guiding the formulation of individualized clinical medication regimens, thereby improving treatment effectiveness and reducing the risk of side effects.

[0080] In some preferred embodiments, see Figure 2 The movable collimation mechanism 303 includes a translation mechanism 304, a collimation frame 305, a projection plate 306, and a collimator switching system 307. The collimation frame 305 is mounted on the translation mechanism 304, which drives the collimation frame 305 to reciprocate to move it to within or outside the effective field of view of the X-ray detector 302. The projection plate 306 and the collimator switching system 307 are arranged opposite each other at both ends of the collimator 305, with the projection plate 306 located at the end of the collimator 305 closer to the X-ray source 301 and the collimator switching system 307 located at the end of the collimator 305 closer to the X-ray detector 302. The projection plate 306 is used to initially shape the X-rays to form an initial X-ray beam, and the collimator switching system 307 is used to switch different collimators 308 to further collimate and adjust the initial X-ray beam to form the X-ray beam required for external beam irradiation.

[0081] Specifically, the translation mechanism 304 can be understood as a linear motion device that provides the collimator 305 with reciprocating movement capability. For example, the translation mechanism 304 can consist of a linear guide rail, a slider, and a drive motor. The drive motor moves the slider on the linear guide rail, thereby switching the collimator 305 within or outside the effective field of view of the X-ray detector. The collimator 305 is a supporting structure used to fix the projection plate 306 and the collimator switching system 307, and moves together with the translation mechanism 304. The projection plate 306 is located at the end of the collimator 305 near the X-ray source 301, and its main function is to perform preliminary shaping of the X-rays to form a preliminary X-ray beam. This preliminary shaping can remove edge scattering in the X-ray beam or confine the X-ray beam to a general area. The collimator switching system 307 is located at the end of the collimator 305 near the X-ray detector 302. Its function is to receive the X-ray beam initially shaped by the projection plate 306 and further finely collimate the initial X-ray beam by switching different collimators 308, ultimately forming an X-ray beam that meets the requirements of external beam radiation therapy. Through this two-stage collimation (initial shaping and further fine adjustment), precise control of the shape, size, and / or intensity of the X-ray beam required for external beam radiation therapy can be achieved (for example, the shape and size of the X-ray beam are determined by the shape and size of the aperture of the collimator 308, and the intensity of the X-ray beam is determined by the transmittance of the collimator 308 to X-rays).

[0082] Specifically, the translation mechanism 304 drives the collimator 305 to reciprocate, ensuring that the collimation components (the parts of the moving collimation mechanism 303 excluding the translation mechanism 304) can enter or exit the effective field of view of the X-ray detector 302 as needed, thus avoiding obstruction during X-ray imaging and providing collimation functionality during external beam radiotherapy. The projection plate 306, as the first-stage collimator, performs preliminary shaping of the X-rays, effectively filtering out some scattered rays and initially defining the range of the X-ray beam, laying the foundation for subsequent fine collimation. The collimator switching system 307, as the second-stage collimator, allows for further shape, size, and / or intensity adjustments to the pre-shaped X-ray beam by switching between different collimators 308, thereby achieving precise control of the X-ray beam required for external beam radiotherapy. This tiered, switchable collimation mechanism enables the system to flexibly generate X-ray beams with specific geometries and energy distributions according to different treatment plans and target area requirements, greatly improving the accuracy and adaptability of radiotherapy.

[0083] Through the above technical solution, this application provides a more structurally complete and functionally powerful mobile collimation mechanism 303. This mechanism, through a translation mechanism 304, enables the flexible entry and exit of the collimation components, ensuring seamless switching between X-ray imaging and external beam radiotherapy modes. More importantly, through the initial shaping of the projection plate 306 and the fine adjustment of the collimator switching system 307, precise and controllable collimation of the X-ray beam required for external beam radiotherapy is achieved, enabling the generation of X-ray beams with specific shapes, sizes, and intensities according to different treatment needs. This significantly improves the accuracy of external beam radiotherapy, reduces damage to surrounding healthy tissues, and thus enhances the accuracy and reliability of the quantification results of the relative bioeffectiveness of radionuclide internal radiation dose.

[0084] In some possible implementations, see Figure 2 The projection plate 306 is provided with a transmission hole 309 for transmitting X-rays to form a preliminary X-ray beam; The collimator switching system 307 includes a switching device on which multiple collimators 308 are installed and a light-transmitting aperture 310 for aligning with the transmission aperture 309. The switching device is used to adjust the position of each collimator 308 so that any one collimator 308 is aligned with the light-transmitting aperture 310, thereby realizing the adjustment of the shape, size and / or intensity of the initial X-ray beam.

[0085] Specifically, the transmission aperture 309 on the projection plate 306 serves as the initial channel for X-rays to pass through the projection plate 306. Its function is to perform preliminary geometric shaping of the X-rays, forming an initial X-ray beam with a specific contour, and to constrain the range of the X-rays, preventing them from passing through locations outside the collimator switching system 307. There can be one or more transmission apertures 309, and their shape and size can be designed according to actual needs, such as circular, square, U-shaped, or irregular shapes, to adapt to the preliminary beam shaping requirements of different treatment scenarios.

[0086] The collimator switching system 307 includes a switching device, multiple collimators 308, and a light-transmitting aperture 310. The multiple collimators 308 are key components for fine collimation of the initial X-ray beam. Each collimator 308 can have different apertures, shapes, or material properties (e.g., X-ray transmittance) to achieve differentiated adjustments to the shape, size, and / or intensity of the X-ray beam. The light-transmitting aperture 310 is located in the collimator switching system 307 and aligned with the transmission aperture 309 on the projection plate 306, serving as the entrance for the initial X-ray beam into the collimator 308. The switching device drives and positions these collimators 308, enabling them to move precisely to the position of the light-transmitting aperture 310. By adjusting the switching device, any preset collimator 308 can be aligned with the light-transmitting aperture 310, thereby selectively further collimating the initial X-ray beam. Its purpose is to precisely control the shape, size, and intensity of the X-ray beam required for the final external beam radiotherapy, according to the requirements of the treatment plan, so as to achieve precise irradiation of the target area.

[0087] Through the above technical solution, this application enables highly precise and flexible adjustment of the shape, size, and / or intensity of the X-ray beam required for external beam radiotherapy. Compared to solutions that only provide preliminary shaping or a single collimation method, this application significantly enhances the customization capability of the X-ray beam by introducing the transmission aperture 309 on the projection plate 306 and multiple switchable collimators 308 in the collimator switching system 307. Therefore, an X-ray beam more suited to treatment needs can be generated based on the actual geometry and location of the tumor in the experimental animal, ensuring that X-ray energy is more precisely concentrated in the target area, minimizing radiation damage to surrounding healthy tissues, and improving the accuracy and effectiveness of external beam radiotherapy.

[0088] In some preferred embodiments, a specific example is illustrated below. Suppose that external beam radiotherapy is required for an irregularly shaped tumor. First, X-rays emitted from an X-ray source pass through a transmission aperture 309 on a projection plate 306, forming an initial X-ray beam. Subsequently, a switching device in a collimator switching system 307 precisely aligns a non-circular collimator with a shape matching the tumor's shape with the aperture 310 according to a pre-set treatment plan. For example, if the tumor is elliptical, a collimator 310 with an elliptical aperture is selected. This non-circular collimator further refines the initial X-ray beam, ultimately forming an X-ray beam that highly conforms to the tumor's shape. If the intensity of the X-ray beam needs adjustment, this can be achieved by selecting collimators 308 of different materials or thicknesses. In this way, it is ensured that the shape, size, and intensity of the X-ray beam precisely match the needs of the target area, thereby achieving highly precise local radiotherapy.

[0089] Furthermore, see Figure 2 The collimator switching system 307 may also include a mounting bracket 311 disposed on the collimator frame 305, and a light-transmitting hole 310 is formed on the mounting bracket 311; The switching device includes a wheel 312 mounted on a mounting bracket 311 and a rotary drive device. The wheel 312 is rotatably connected to the mounting bracket 311, and a plurality of collimators 308 are evenly arranged on the wheel 312 along the circumference. The rotary drive device is used to drive the wheel 312 to rotate so that any one of the collimators 308 is aligned with the light-transmitting hole 310.

[0090] Specifically, the mounting bracket 311 is a structure fixed to the collimator 305, providing a mounting base for the wheel 312 and the rotary drive device. For example, the mounting bracket 311 can be adopted... Figure 2 The U-shaped frame is used, but is not limited to. A light-transmitting aperture 310 is formed on the mounting bracket 311, aligned with the transmission aperture 309 on the projection plate 306, ensuring the initial X-ray beam can pass through. The core components of the switching device are the wheel 312 and the rotary drive device. The wheel 312 is rotatably connected to the mounting bracket 311, and multiple collimators 308 of different specifications are evenly arranged around its circumference. These collimators 308 can be designed in different shapes, sizes, or materials according to actual needs to achieve fine adjustment of the X-ray beam. The rotary drive device, such as a stepper motor or servo motor, is used to precisely control the rotation of the wheel 312, so that any preset collimator 308 can be accurately aligned with the light-transmitting aperture 310.

[0091] The solution of this application pre-mounts multiple collimators 308 on a wheel 312 and uses a rotary drive device to precisely control the rotation of the wheel 312. This allows the wheel 312 to be rotated to the appropriate position simply when a collimator 308 needs to be switched. This design avoids the problems of long switching times and low positioning accuracy associated with traditional manual replacement or complex linear movement mechanisms. When a specific shape, size, or intensity of X-ray beam is required, the rotary drive device drives the wheel 312 to rotate, precisely aligning the corresponding collimator 308 with the light-transmitting aperture 310, thereby achieving rapid and accurate formation of the X-ray beam required for external irradiation radiotherapy.

[0092] Through the above technical solution, the collimator switching system 307 can achieve rapid and precise switching of multiple collimators 308, greatly improving the efficiency and accuracy of X-ray beam adjustment during external beam radiotherapy. This rotary switching mechanism is compact and easy to operate, effectively shortening treatment preparation time and ensuring the switching positioning accuracy between different collimators 308, thereby guaranteeing the precision and reliability of external beam radiotherapy.

[0093] If the posture or angle of the experimental animal cannot be adjusted during SPECT imaging or external beam radiation therapy, it may result in incomplete imaging data or make it difficult to achieve multi-angle and uniform irradiation of the target area during external beam radiation therapy, thereby affecting the accuracy of dose quantification and the realism of treatment simulation.

[0094] Therefore, in some preferred embodiments, the movable bed 2 can also drive the experimental animal to rotate about a front-to-back axis, and / or the X-ray detection system 3 can rotate about the front-to-back axis.

[0095] Specifically, the mobile bed 2 is designed not only to enable translational movement of the experimental animal but also to allow it to rotate around an axis extending in the front-back direction. This axis is typically roughly parallel to the animal's body axis, allowing the animal to rotate 360 ​​degrees along its longitudinal axis. This rotational capability can be understood as enabling more precise positioning and posture adjustment of the experimental animal in three-dimensional space, with the aim of providing more comprehensive projection data for SPECT imaging and more diverse irradiation angles for external beam radiation therapy. Similarly, when the X-ray detection system 3 can rotate around this axis, adjusting the rotation angle of the X-ray detection system 3 can also provide more diverse irradiation angles for external beam radiation therapy.

[0096] This application's solution effectively overcomes the limitations of single translational motion in imaging and treatment simulation by endowing the movable bed 2 with rotational capability. When experimental animals require SPECT imaging, the rotation of the movable bed 2 allows the SPECT detection system 4 to acquire projection data from various angles of the experimental animal, thereby obtaining a more complete and accurate three-dimensional nuclide distribution image in subsequent image reconstruction. Furthermore, during X-ray imaging, imaging can be performed from multiple different angles (both X-ray plain film imaging and CT imaging) to better assist in the reconstruction of the three-dimensional nuclide distribution image. During external beam radiotherapy, the rotational function of the movable bed 2 enables the X-ray detection system 3 to irradiate the target area from multiple angles. This is crucial for achieving intensity-modulated radiotherapy (IMRT), ensuring that the X-ray beam can more accurately cover the tumor area while maximizing the protection of surrounding healthy tissue. Similarly, when the X-ray detection system 3 can rotate around its extended axis, adjusting the rotation angle of the X-ray detection system 3 can also provide more diverse irradiation angles for external beam radiotherapy. It is precisely this rotational capability that enables the system to more realistically simulate clinical treatment scenarios and obtain more accurate dosimetric data.

[0097] Through the aforementioned technical solutions, the radionuclide internal irradiation dose-to-bioeffectiveness quantification system of this application can significantly improve the positioning flexibility and accuracy of experimental animals during imaging and treatment. Specifically, the rotation function enables SPECT imaging to obtain more comprehensive three-dimensional information and can also achieve CT imaging; the combination of the two improves the accuracy of radionuclide distribution quantification. Simultaneously, during external irradiation radiotherapy, multi-angle, conformal intensity-modulated irradiation can be achieved, thereby more accurately simulating the clinical radiotherapy process and ensuring the uniformity of X-ray dose distribution and the accuracy of target coverage. Therefore, this application can provide more reliable and refined data support for the quantification of radionuclide internal irradiation dose-to-bioeffectiveness, thereby improving the scientific validity and clinical translational value of the research results.

[0098] For example Figure 3 The present invention provides a structure that enables the rotation of a mobile bed 2. Specifically, the mobile bed 2 includes a three-axis translation mechanism 201, a rotation drive mechanism 202, and an animal bed 203. The animal bed 203 is connected to the three-axis translation mechanism 201 through the rotation drive mechanism 202. The three-axis translation mechanism 201 can drive the animal bed to move in the front-back, left-right, and up-down directions. The rotation drive mechanism 202 is used to drive the animal bed 203 to rotate around the aforementioned front-back extended axis. The animal bed 203 is used to fix the experimental animal.

[0099] The three-axis translation mechanism 201 can be understood as a mechanical device capable of providing linear movement in three orthogonal directions (e.g., X, Y, and Z axes). Specifically, it can consist of multiple linear guides, stepper motors or servo motors, and corresponding drive control units to achieve precise translational positioning of the animal bed in space. Figure 3 In this system, the three-axis translation mechanism 201 consists of a Z-axis movement mechanism 204, an X-axis movement mechanism 205, and a Y-axis movement mechanism 206. Its purpose is to precisely move the experimental animal to the X-ray irradiation system 3 and the SPECT detection system 4, and to perform fine spatial adjustments within these positions.

[0100] The rotary drive mechanism 202 can be understood as a mechanical device capable of providing rotational motion. Specifically, it may consist of a rotating platform, a rotary motor (such as a stepper motor or servo motor), and corresponding transmission components, used to drive the animal bed 203 to rotate around a front-to-back axis. Its purpose is to enable experimental animals to face the X-ray source 301 or the SPECT probe 401 at different angles, thereby achieving multi-angle X-ray imaging, external beam radiation therapy, or SPECT imaging.

[0101] Animal bed 203 is a carrier used to immobilize laboratory animals. Its design should ensure the stability of the animals during movement and rotation, avoiding any impact on the accuracy of imaging and treatment due to animal movement. In practical applications, animal bed 203 can be made of X-ray resistant material and can be equipped with animal anesthesia and vital sign monitoring devices to ensure the safety and stability of the laboratory animals during experiments.

[0102] The solution in this application cleverly combines a three-axis translation mechanism 201 with a rotational drive mechanism 202, and connects the animal bed 203 to the three-axis translation mechanism 201 via the rotational drive mechanism 202. This achieves decoupling and coordinated control of the experimental animal's translational motion in three-dimensional space and its rotational motion around the forward and backward extension axes. Specifically, when it is necessary to move the experimental animal from one workstation to another, the three-axis translation mechanism 201 is responsible for large-scale spatial positioning; when it is necessary to perform multi-angle imaging or irradiation of the experimental animal at a specific workstation, the rotational drive mechanism 202 is responsible for providing precise rotation angle adjustment. This structural design makes the positioning and posture adjustment of the experimental animal more flexible and precise, and can meet the stringent requirements for high-precision positioning and multi-angle data acquisition in the process of quantifying the relative bioeffectiveness of radionuclide drug internal irradiation dose.

[0103] To enable the rotation of the X-ray detection system 3, a rotating support can be installed on the frame 1, and the X-ray detection system 3 can be mounted on this rotating support. For example, the rotating support includes an annular track fixedly connected to the frame 1, with its central axis coinciding with the aforementioned front-to-back extending axis. An annular frame or a C-shaped frame is slidably mounted on this annular track, and the X-ray detection system 3 is mounted on this annular frame or C-shaped frame. However, the method of enabling the rotation of the X-ray detection system 3 is not limited to this.

[0104] The SPECT detection system 4 can employ one or more SPECT probes 401, and the SPECT probes 401 can be fixed or adjustable in position.

[0105] When using only a single or fixed-position SPECT probe 401, it may be difficult to fully utilize the rotational movement of the experimental animal, resulting in low imaging efficiency or limited imaging quality at certain angles, thus affecting the accurate quantification of the relative bioeffectiveness of the internal irradiation dose of radiopharmaceuticals.

[0106] Therefore, more preferably, see Figure 4 The SPECT detection system 4 may include a plurality of SPECT probes 401 evenly arranged circumferentially along the aforementioned front-to-back axis. Each SPECT probe 401 is connected to the frame 1 via a radial motion mechanism 402, which is used to adjust the radial position of the SPECT probe 401 relative to the front-to-back axis.

[0107] Specifically, "multiple SPECT probes 401" means that the SPECT detection system 4 is not composed of a single probe, but rather of two or more independent SPECT probes 401 that work together to obtain images of the radioactivity distribution in experimental animals.

[0108] "Uniformly arranged circumferentially along the aforementioned front-to-back axis" means that these SPECT probes 401 are distributed in a ring or semi-ring shape around the axis of rotation of the experimental animal (i.e., the front-to-back axis), and are equally spaced from each other in the circumferential direction, to ensure omnidirectional or wide-angle detection of the experimental animal. This arrangement helps to acquire data simultaneously or quickly from multiple angles while the experimental animal is rotating, improving imaging efficiency and coverage.

[0109] The "radial motion mechanism 402" can be understood as a mechanical device that drives the SPECT probe 401 to move radially (i.e., in a direction perpendicular to the front-to-back axis). For example, this mechanism may include components such as guide rails, sliders, stepper motors, or servo motors. By precisely controlling the movement of the motors, the radial displacement of the probe is achieved. Its purpose is to adjust the distance between the SPECT probe 401 and the experimental animal to accommodate experimental animals of different sizes, or to adjust the spatial resolution and sensitivity according to imaging requirements. By adjusting the radial position, the geometric relationship between the detector and the target area can be optimized, thereby obtaining clearer and more accurate SPECT images.

[0110] The solution presented in this application effectively addresses the limitations of single or fixed probes in rotating imaging of experimental animals by employing multiple SPECT probes 401 arranged circumferentially along an axis extending front-to-back, and equipping each probe with a radial motion mechanism 402. Because multiple probes can simultaneously or rapidly acquire data from different angles, imaging time is significantly shortened, and data acquisition efficiency is improved. Simultaneously, the circumferentially evenly arranged probes ensure comprehensive coverage of the experimental animal, avoiding image information loss due to angle limitations. Furthermore, the introduction of the radial motion mechanism 402 allows each SPECT probe 401 to flexibly adjust its distance from the experimental animal according to its size or specific imaging requirements. This adjustability ensures that the detector remains in the optimal imaging position under different experimental conditions, thereby optimizing spatial resolution and detection sensitivity, and ensuring high-quality SPECT image acquisition. Through these synergistic effects, the SPECT detection system 4 of this application can acquire radionuclide distribution information within the experimental animal more efficiently and accurately, providing a reliable data foundation for subsequent dose calculations.

[0111] The above description is merely an embodiment of this application and is not intended to limit the scope of protection of this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the scope of protection of this application.

Claims

1. A method for quantifying the relative bioavailability of internal radiation dose to radiopharmaceuticals, characterized in that, The method includes the following steps: A1. Divide the same batch of experimental animals carrying tumors into two groups. Inject the first group of experimental animals with different doses of the test therapeutic radionuclide drug, and inject the second group of experimental animals with a contrast radionuclide drug. The contrast radionuclide drug is a diagnostic radionuclide drug paired with the test therapeutic radionuclide drug or a reduced dose of the test therapeutic radionuclide drug. A2. For each experimental animal in the first group, the radiation absorbed dose of the therapeutic radionuclide drug to the target area was determined by SPECT imaging and X-ray imaging; A3. For each experimental animal in the second group, external beam radiotherapy was performed on the target area by SPECT imaging and / or X-ray imaging guided by X-rays. A4. Obtain radiation damage information and / or radiation response information for each experimental animal; A5. Compare the radiation damage information and / or radiation response information of the target area of ​​the two groups of experimental animals, and pair the radiation absorbed dose with the X-ray irradiation dose with similar radiation damage information and / or radiation response information; A6. Calculate the relative bioavailability of the internal radiation dose of the therapeutic radionuclide drug under test based on the paired radiation absorbed dose and the X-ray irradiation dose.

2. The method for quantifying the relative bioavailability of radiopharmaceutical internal irradiation dose according to claim 1, characterized in that, Step A2 includes: A201. SPECT and X-ray imaging were performed on the experimental animals in the first group to obtain the first SPECT image and the first X-ray image; A202. Identify the target region based on the first SPECT image and the first X-ray image; A203. Based on the first SPECT image, the radiation absorbed dose of the therapeutic radionuclide drug to the target area is calculated using a dose estimation model.

3. The method for quantifying the relative bioavailability of radiopharmaceutical internal irradiation dose according to claim 1, characterized in that, Step A3 includes: A301. Perform SPECT imaging and / or X-ray imaging on the experimental animals in the second group to obtain a second SPECT image and / or a second X-ray image; A302. Determine the three-dimensional location of the target area based on the second SPECT image and / or the second X-ray image; A303. Based on the three-dimensional position of the target area and the required X-ray irradiation dose, determine the X-ray beam size and intensity at multiple different irradiation angles for the target area; A304. Based on the three-dimensional position of the target area and the determined X-ray beam size and intensity at multiple different irradiation angles, perform multi-angle conformal intensity-modulated irradiation on the target area.

4. The method for quantifying the relative bioavailability of radiopharmaceutical internal irradiation dose according to claim 1, characterized in that, The radiation damage information includes at least one of the following: changes in tumor volume, changes in body weight, routine blood indicators, and histopathological examination results.

5. The method for quantifying the relative bioavailability of radiopharmaceutical internal irradiation dose according to claim 1, characterized in that, The radiation response information includes at least one of the following: the degree of tumor remission and the time of disease progression.

6. The method for quantifying the relative bioavailability of radiopharmaceutical internal irradiation dose according to claim 1, characterized in that, Step A5 includes: A501. After normalizing the radiation damage information and / or radiation response information of the target area of ​​each experimental animal, a biological effect data set is formed. A502. Calculate the Euclidean distance between the biological effect data sets of each experimental animal in the first group and each experimental animal in the second group; A503. Compare the Euclidean distance with a preset distance threshold to determine whether the radiation damage information and / or radiation response information of the two experimental animals are similar, and determine that the two experimental animals with similar radiation damage information and / or radiation response information are paired experimental animals; A504. Pair the radiation absorbed dose of the experimental animals belonging to the first group with the X-ray irradiation dose of the experimental animals belonging to the second group.

7. The method for quantifying the relative bioavailability of radiopharmaceutical internal irradiation dose according to claim 6, characterized in that, Step A504 includes: The experimental animals belonging to the first group and the second group in the paired experimental animals were respectively designated as the first paired animal and the second paired animal. If the same first-paired animal successfully pairs with only one second-paired animal, then the radiation absorbed dose and the X-ray irradiation dose of the corresponding two experimental animals are paired. If the same first paired animal is successfully paired with multiple second paired animals, the weighting coefficient of each second paired animal is determined based on the Euclidean distance between the biological effect data sets of the same first paired animal and each second paired animal, and the weighted average of the X-ray irradiation dose of each second paired animal is calculated based on the weighting coefficient. The radiation absorbed dose of the same first paired animal is then paired with the weighted average.

8. The method for quantifying the relative bioavailability of radiopharmaceutical internal irradiation dose according to claim 1, characterized in that, Step A6 includes: A601. For each pair of radiation absorbed dose and X-ray irradiation dose, calculate the quotient of the radiation absorbed dose and the X-ray irradiation dose to obtain the preliminary internal irradiation dose relative bioavailability. A602. By combining the relative bioavailability of each preliminary internal irradiation dose, the relative bioavailability of the internal irradiation dose of the therapeutic radionuclide drug to be tested is calculated.

9. A system for quantifying the relative bioavailability of internal radiation dose of a radiopharmaceutical, used to implement the method for quantifying the relative bioavailability of internal radiation dose of a radiopharmaceutical according to any one of claims 1-8; characterized in that, The radiopharmaceutical internal irradiation dose relative bioeffectiveness quantification system includes a host computer and a frame (1), and also includes a moving bed (2), an X-ray irradiation system (3) and a SPECT detection system (4) arranged sequentially on the frame (1) in the front-back direction. The movable bed (2) is used to move the experimental animal between the X-ray irradiation station of the X-ray irradiation system (3) and the detection station of the SPECT detection system (4); The SPECT detection system (4) is used to perform SPECT imaging on the experimental animals; The X-ray detection system (3) includes an X-ray source (301) and an X-ray detector (302) arranged opposite to each other, and a movable collimation mechanism (303) disposed between the X-ray source (301) and the X-ray detector (302); the X-ray source (301) is capable of emitting a first X-ray for X-ray imaging and a second X-ray for external irradiation radiotherapy, wherein the power of the second X-ray is greater than the power of the first X-ray; the movable collimation mechanism (303) is capable of moving into the effective field of view of the X-ray detector (302) to collimate and adjust the X-rays to form the X-ray beam required for external irradiation radiotherapy; the movable collimation mechanism (303) is also capable of moving out of the effective field of view of the X-ray detector (302) to avoid obstructing X-ray imaging; The host computer is used to control the operation of the moving bed (2), the X-ray irradiation system (3) and the SPECT detection system (4) to determine the relative bioeffectiveness of the internal irradiation dose of the therapeutic radionuclide drug.

10. The radiopharmaceutical internal irradiation dose relative bioavailability quantification system according to claim 9, characterized in that, The movable collimation mechanism (303) includes a translation mechanism (304), a collimation frame (305), a projection plate (306), and a collimator switching system (307); the collimation frame (305) is mounted on the translation mechanism (304), and the translation mechanism (304) is used to drive the collimation frame (305) to reciprocate to move to within or outside the effective field of view of the X-ray detector (302); The projection plate (306) and collimator switching system (307) are disposed opposite to each other at both ends of the collimator frame (305), with the projection plate (306) located at the end of the collimator frame (305) closer to the X-ray source (301) and the collimator switching system (307) located at the end of the collimator frame (305) closer to the X-ray detector (302). The projection plate (306) is used to preliminarily shape the X-rays to form a preliminary X-ray beam, and the collimator switching system (307) is used to switch different collimators (308) to further collimate and adjust the preliminary X-ray beam to form the X-ray beam required for external beam radiation therapy.

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