A radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions

Abstract

The application belongs to the technical field of nitrogen-proton therapy, and relates to a radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reaction, which comprises a proton beam precision irradiation device rotatably installed on the side of a shielding wall of a radiation shielding and safety interlocking system, used for generating a proton beam precisely incident to a tumor lesion area with nitrogen-15 aggregation in a human body; a six-dimensional adjustment treatment bed arranged in the irradiation range of the proton beam precision irradiation device, used for carrying and positioning a patient; a nitrogen-15 glutamine targeted drug delivery auxiliary assembly, used for realizing precise targeted drug delivery of nitrogen-15 labeled glutamine in the tumor lesion area; and a real-time nuclear reaction and dose monitoring system electrically linked with the proton beam precision irradiation device and the nitrogen-15 glutamine targeted drug delivery auxiliary assembly. Thus, the shortcomings of the prior art in the precision of targeted drug delivery, real-time monitoring and feedback regulation of in-vivo nuclear reaction, and shielding of a complex mixed radiation field can be overcome.

Description

Technical Field

[0001] This invention relates to the field of nitrogen-proton therapy technology, and more specifically, to a radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions. Background Technology

[0002] With the development of nuclear physics and clinical radiotherapy techniques, proton therapy, as an advanced radiotherapy method, is increasingly widely used in clinical practice due to its unique Bragg peak dose distribution characteristics, which precisely deposits the majority of energy into the target lesion area while the radiation dose to normal tissues at the incident and exit points is extremely low. However, limited by the relative biological effects of protons themselves, existing proton therapy systems, when facing certain hypoxic or radiation-resistant tumor cells, still have certain limitations in biological killing efficiency when relying solely on physical dose action to kill tumor cells. This requires increasing the radiation dose to compensate, but this inevitably increases the risk of radiation damage to surrounding normal tissues, resulting in a limited therapeutic gain ratio and making it difficult to meet the higher standards of precision treatment needs.

[0003] In the exploration of improving treatment specificity, the therapeutic strategy of combining radionuclide-labeled tumor-targeting drugs with in vitro particle beam-triggered nuclear reactions has theoretically shown unique advantages. However, to translate this strategy into a stable clinical treatment system, existing technologies have revealed shortcomings and challenges in at least three aspects.

[0004] Firstly, in terms of targeted drug delivery and radionuclide enrichment, there is a lack of dedicated auxiliary equipment capable of achieving high-precision, quantitative, and stable injection for different tumor lesion locations in different patients. Relying on traditional manual injection not only limits injection accuracy to the operator's experience, but also makes the injection needle prone to deviation due to unavoidable factors such as respiratory movements and hand tremors. This makes it difficult for the radionuclide drug to achieve the expected high concentration enrichment in the tumor lesion area, thereby directly reducing the targeting effectiveness of the nuclear reaction and the efficiency of subsequent treatment.

[0005] At the level of radiation-induced and real-time control, current proton therapy systems primarily rely on indirect external monitoring of the physical parameters of the incident proton beam (such as flux, energy, beam intensity, irradiation time, and dose distribution) to estimate the absorbed dose within the target area. However, for treatment modalities that trigger nuclear reactions within the body using proton beams, the effectiveness of the treatment directly depends on the amount of nuclear reactions occurring (i.e., alpha particles and...). 12The current system lacks an in-situ feedback mechanism that can directly and non-invasively monitor the nuclear reaction process within the body. This prevents doctors from assessing the actual occurrence of the nuclear reaction in real time and quantitatively, and thus from dynamically adjusting the proton beam parameters based on real-time feedback on the treatment effect. This results in an "open-loop" state of treatment dosage: insufficient nuclear reaction leads to incomplete treatment, while excessive nuclear reaction may cause accidental damage to normal tissues near the target area due to overproduction of alpha particles, severely limiting the safety and effectiveness of treatment.

[0006] In terms of radiation safety and shielding design, the proton-induced nitrogen-15 nuclear reaction radiotherapy mode involves direct, scattered, and leaky high-energy proton beams, resulting in an extremely complex radiation field composition and spatial distribution. Traditional proton therapy room shielding structures are mostly designed to protect against a single proton beam, failing to provide comprehensive, blind-spot-free effective shielding for this mixed radiation field. Designing a multi-layered shielding system that can efficiently shield multiple types of radiation while also accommodating the complex mechanical movements of treatment equipment (such as the rotation of the proton beam collimator) and the individualized positioning needs of patients is another key challenge in ensuring radiation safety for both medical staff and patients, and guaranteeing the clinical feasibility of the system.

[0007] In summary, to overcome the shortcomings of existing technologies in terms of targeted drug delivery accuracy, real-time monitoring and feedback regulation of nuclear reactions in vivo, and shielding of complex mixed radiation fields, a radiotherapy system based on proton-induced nitrogen-15 nuclear reactions is still needed. This system should be able to achieve synergistic effects in areas such as precise delivery of nitrogen-15 targeted drugs, precise proton beam irradiation induction, real-time monitoring and feedback regulation of nuclear reactions in vivo, and comprehensive shielding of mixed radiation fields, thereby improving the controllability, safety, and stability of the treatment process. Summary of the Invention

[0008] The purpose of this invention is to overcome the above-mentioned defects in the prior art and propose a radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions, so as to overcome the shortcomings of the prior art in terms of targeted drug delivery accuracy, real-time monitoring and feedback regulation of nuclear reactions in vivo, and shielding of complex mixed radiation fields.

[0009] To achieve the above objectives, the present invention provides the following technical solution:

[0010] A radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions is disclosed. This system is configured for use in conjunction with a nitrogen-15-labeled preparation to collect data on the reaction during proton beam irradiation of a predetermined target area. 15The accompanying gamma-ray signal associated with the N(p,α)¹²C nuclear reaction is used to adjust the proton beam parameters in real time based on the accompanying gamma-ray signal; the nitrogen-15 labeled preparation is a nitrogen-15 labeled glutamine preparation used to label tumor lesions with nitrogen-15 to enhance the local radiobiological effect in the tumor lesion area.

[0011] The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions includes:

[0012] A proton beam precision irradiation device, rotatably mounted on the shielding wall of a radiation shielding and safety interlocking system, is used to generate a proton beam precisely incident on the tumor lesion area where nitrogen-15 accumulates within the human body. This allows the proton beam to spatially match the nitrogen-15-enriched labeled drug within the tumor lesion area, thereby inducing irradiation within the human body. 15 Nuclear reactions of N(p,α)¹²C;

[0013] The six-dimensional adjustable treatment bed is set within the irradiation range of the proton beam precision irradiation device and is used to support the patient and adjust the patient's position so that the tumor lesion area is aligned with the proton beam irradiation area.

[0014] A nitrogen-15-glutamine targeted drug delivery aid component for achieving precise targeted drug delivery of nitrogen-15-labeled glutamine to the tumor lesion area;

[0015] The real-time nuclear reaction and dose monitoring system is electrically linked to the proton beam precision irradiation device and the nitrogen-15-glutamine targeted drug delivery auxiliary component;

[0016] The real-time nuclear reaction and dose monitoring system is configured to monitor the proton beam irradiation dose and the nuclear reaction process in the body, and adjust the proton beam parameters of the proton beam precision irradiation device according to the monitoring results.

[0017] In one alternative embodiment, the proton beam precision irradiation device includes a proton accelerator, an energy selection system, a beam transport vacuum tube, a beam parameter control component, and a rotatable proton beam collimator.

[0018] The proton accelerator is a cyclotron or synchrotron, which generates a therapeutic proton beam.

[0019] The energy selection system is connected to the beam extraction end of the proton accelerator;

[0020] The beam transmission vacuum tube passes horizontally through the shielding wall, with one end connected to the energy selection system and the other end connected to the rotatable proton beam collimator.

[0021] The beam parameter control component is electrically connected to the proton accelerator, the energy selection system, and the real-time nuclear reaction and dose monitoring system.

[0022] In one alternative embodiment, the rotatable proton beam collimator is rotatably mounted on one side of the shielding wall via a gyroscopic support;

[0023] The inner ring of the gyro bearing is fixedly connected to the shielding wall, and the outer ring is fixedly connected to the rotatable proton beam collimator. The rotatable proton beam collimator can achieve stepless rotation from 0 to 360° through the gyro bearing to adjust the incident angle of the proton beam.

[0024] And / or, the rotatable proton beam collimator is made of a composite material of lead and zirconium boride; it has a conical hollow channel inside, and the inner wall of the channel has a boron-containing neutron absorption layer, which is used to define the shape of the proton beam, limit the irradiation range of the proton beam and reduce the beam edge scattering radiation.

[0025] In one optional embodiment, the beam parameter control component includes an energy regulation module and a flux regulation module;

[0026] The energy adjustment module is connected to the energy selection system and is used to adjust the incident energy of the proton beam;

[0027] The proton beam flux density adjustment range of the flux adjustment module is 10. 8 ~10 10 ·cm -2 ·s -1 ;

[0028] The flux regulation module is also used to receive feedback signals from the real-time nuclear reaction and dose monitoring system to achieve closed-loop regulation of flux density.

[0029] In one optional embodiment, the six-dimensional adjustable treatment bed includes a bed body, a lifting assembly, a horizontal movement assembly, a rotation assembly, and a body position fixing assembly;

[0030] The bed is used to accommodate the patient;

[0031] The lifting assembly is used to adjust the position of the bed in the vertical direction;

[0032] The horizontal movement component is used to adjust the position of the bed in the left-right and front-back directions;

[0033] The rotating assembly is used to adjust the attitude of the bed about the X-axis, Y-axis and / or Z-axis;

[0034] The positioning fixation component is used to fix the patient's position and includes one or more of the following: a malleable soft pad, a thermoplastic film, a medical fixation strap, a head, neck and shoulder fixation frame, and a trunk positioning frame.

[0035] In one optional embodiment, the radiation shielding and safety interlocking system includes a shielding wall, a treatment room shielding layer, a local shielding component for the non-lesion area of ​​the patient, a beam transmission pipeline through-wall shielding sleeve, and a collimator connection end shielding cover.

[0036] The shielding wall is used to enclose the treatment room. The shielding wall is a composite concrete wall with 5% boron powder and 3% tungsten powder added inside.

[0037] The shielding layer of the treatment room is provided on the walls, floor and / or ceiling of the treatment room;

[0038] The local shielding component for non-lesion areas of the patient is used to fit and be placed on the non-lesion areas of the patient's body surface;

[0039] The beam transmission pipeline through-wall shielding sleeve is installed at the location where the beam transmission pipeline passes through the shielding wall;

[0040] The collimator connection end shield is located in the connection area between the rotatable proton beam collimator and the shielding wall.

[0041] In one optional embodiment, the full-area shielding layer of the treatment room is an 8-10cm thick boron polyethylene board, which is fully covered on the walls, floor and ceiling of the treatment room, and its shielding efficiency for scattered protons is greater than 99%.

[0042] The entrance to the treatment room is equipped with a double-layer lead plate with a 5cm thick boron polyethylene shielding door sandwiched in between, and is also equipped with a radiation interlocking device for automatic locking when the proton beam is turned on.

[0043] The through-wall shielding sleeve is a composite structure of double-layer boron polyethylene and lead core, used to absorb thermal neutrons and attenuate gamma rays.

[0044] The shield is a composite structure with a stainless steel outer shell and a 10cm thick boron polyethylene lining, and it rotates coaxially with the rotatable proton beam collimator.

[0045] In one optional embodiment, the real-time nuclear reaction and dose monitoring system includes:

[0046] A gamma-ray nuclear reaction monitoring unit is used to capture the¹ 5 The characteristic γ-rays in the 4.4 MeV energy range generated by ¹²C deexcitation during the N(p,α)¹²C nuclear reaction were used to monitor the nuclear reaction process in situ.

[0047] The data processing module is used to estimate the occurrence of nuclear reactions in the body based on the gamma-ray signal and the proton beam dose parameters;

[0048] The feedback control module is electrically connected to the beam parameter control component in the proton beam precision irradiation device and is used to send control signals based on the calculation results.

[0049] In one optional embodiment, the gamma-ray nuclear reaction monitoring unit includes four gamma-ray detectors arranged in a ring array around the treatment room at a distance of 100 cm from the tumor lesion target area.

[0050] The gamma-ray detector is a NaI(Tl) scintillator detector with an energy response range of 0.5–10 MeV, a detection efficiency of more than 20% for gamma rays in the 4.4 MeV energy range, and a response time of ≤10 ms.

[0051] Each of the gamma-ray detectors is equipped with a lead collimation sleeve and is fixed by an adjustable bracket with an installation accuracy of ±1cm.

[0052] The detection efficiency, geometric response, and energy response of the gamma-ray detector are obtained through at least one of standard source calibration or Monte Carlo simulation.

[0053] In one alternative implementation, the data processing module is configured to:

[0054] The count rate of characteristic gamma rays in the 4.4 MeV energy region measured by the gamma-ray nuclear reaction monitoring unit was obtained, and the count rate was determined according to the nuclear physics formula R. 反应 =N γ / (ε·Ω·P), converting the count rate into ¹ in vivo. 5 N(p,α)¹²C nuclear reaction rate R 反应 ,in Ω represents the detector's absolute detection efficiency, P represents the detector's solid angle relative to the reaction source, and P represents the branching ratio of the characteristic γ-rays emitted in the 4.4 MeV energy range during the ¹¹²C de-excitation process.

[0055] In one alternative implementation, the feedback control module is configured as follows:

[0056] The nuclear reaction rate or relative intensity distribution of nuclear reactions estimated by the data processing module is compared with a preset target range.

[0057] When the nuclear reaction rate or the relative intensity distribution of the nuclear reaction is lower than a preset lower limit, an enhanced irradiation signal is sent to the proton beam irradiation device.

[0058] When the nuclear reaction rate or the relative intensity distribution of the nuclear reaction is higher than a preset upper limit, a suppression irradiation signal or a beam shut-off signal is sent to the proton beam irradiation device.

[0059] When the nuclear reaction and dose online monitoring system detects detector abnormalities, dose rate abnormalities, beam spot position abnormalities, or treatment room interlocking abnormalities, it sends a safety shutdown command to the proton beam irradiation device.

[0060] In one optional embodiment, the nitrogen-15-glutamine targeted drug delivery auxiliary component includes a micro-precision injection unit, a targeted positioning and fixation unit, a drug isothermal storage unit, and a drug delivery parameter control unit;

[0061] The micro-precision injection unit, including a medical micro-injection pump, a sterile injection syringe, and a disposable anti-leakage injection needle, is used to achieve quantitative injection of the preparation.

[0062] The targeted positioning and fixation unit includes a medical adjustable positioning frame, a lesion-fitting fixation base, and a three-dimensional micro-adjustment clamp for the needle body, which is used to position and fix the injection needle body in the tumor lesion target area, with an overall positioning accuracy of ±0.05mm.

[0063] A drug constant-temperature storage unit, which is a medical-grade low-temperature constant-temperature storage structure, is used to store nitrogen-15-glutamine preparations at a constant temperature of 2~8℃; and

[0064] A drug administration parameter control unit, which is electrically connected to the micro-precision injection unit, is used to set and control injection parameters.

[0065] In one alternative implementation, the micro-precision injection unit:

[0066] The medical micro-infusion pump is a medical-grade high-precision plunger-type structure with a radiation-proof ABS shell. Its injection speed adjustment range is 0.1~10mL / h, and the dose control accuracy is ±0.01mL.

[0067] The disposable anti-leakage injection needle has a micro-sized drug dispensing hole on the side wall of the needle tube, and its needle seat is equipped with an anti-leakage sealing ring.

[0068] In one alternative implementation, the targeting and positioning unit includes:

[0069] The medical adjustable positioning frame is used to connect the lesion-fitting fixing base and the needle body three-dimensional fine-tuning clamp;

[0070] The lesion-fitting fixation base is made of medical-grade flexible silicone material with embedded shaped metal wires.

[0071] The needle body three-dimensional micro-adjustment fixture can achieve micron-level micro-adjustment in X / Y / Z axes with an adjustment accuracy of ±0.1mm to adapt to injection needles of different diameters.

[0072] In one optional embodiment, the dosing parameter control unit includes:

[0073] An embedded data processor is used to store patient drug administration parameters and perform closed-loop control of injection speed and dosage. When the actual parameters deviate from the set parameters by more than ±0.1%, an alarm is triggered and automatic correction is performed.

[0074] The wireless communication module is used to transmit data between the data processor and the remote control terminal;

[0075] The alarm module is used to issue an alarm signal when the actual injection speed, actual injection dose, needle position, or drug storage temperature exceeds a preset threshold, and to pause the injection or prompt the operator to make corrections.

[0076] In one optional embodiment, the shielding wall is a composite shielding structure formed from one or more of the following materials: boron-containing materials, tungsten-containing materials, heavy concrete, ordinary concrete, lead plate, polyethylene materials, and boron-polyethylene materials. In another optional embodiment, the shielding layer of the treatment room includes one or more of the following: a neutron moderation layer, a neutron absorption layer, and a gamma-ray shielding layer.

[0077] The neutron moderation layer includes a polyethylene layer;

[0078] The neutron absorbing layer includes a boron-containing polyethylene layer, which is installed on the walls, floor and ceiling of the treatment room to shield scattered neutrons.

[0079] The gamma-ray shielding layer of the beam transmission vacuum tube includes a lead layer, a tungsten layer, a steel plate layer, or a heavy concrete layer; the through-wall shielding sleeve is a composite structure of double-layer boron polyethylene and a lead core.

[0080] The collimator connection end shield is a stainless steel shell lined with 10cm thick boron polyethylene, and it rotates coaxially with the rotatable proton beam collimator.

[0081] Compared with the prior art, the present invention has at least the following beneficial effects:

[0082] First, by setting up a nitrogen-15 labeled glutamine targeted drug delivery auxiliary component, the present invention can help realize the quantitative and localized delivery of nitrogen-15 labeled glutamine preparations to the tumor lesion area, which is beneficial to improve the controllability of the enrichment of nitrogen-15 labeled drugs in the tumor lesion area, thereby providing a more stable target material basis for subsequent proton beam-triggered nitrogen-15 nuclear reactions.

[0083] Secondly, by combining a proton beam precision irradiation device with a six-dimensional adjustable treatment bed, this invention can adjust the proton beam energy, flux density, irradiation angle, and patient position according to the location, depth, and morphology of the tumor lesion area. This allows for better spatial matching between the proton beam irradiation area and the nitrogen-15 labeled drug enrichment area, which is beneficial for improving the accuracy of proton beam irradiation-triggered nuclear reactions and the stability of treatment implementation.

[0084] Third, this invention, based on traditional proton beam dose monitoring, introduces a real-time nuclear reaction and dose monitoring system, through the acquisition and¹ 5 The system uses gamma-ray signals related to the N(p,α)¹²C nuclear reaction to estimate the occurrence of nitrogen-15 nuclear reactions in vivo. Therefore, the system can not only monitor the physical dose parameters of the incident proton beam but also obtain feedback information reflecting the progress of nuclear reactions in vivo, which is beneficial for improving the monitorability and evaluability of the treatment process.

[0085] Fourth, by linking the real-time nuclear reaction and dose monitoring system with the beam parameter control component in the proton beam precision irradiation device, this invention enables feedback adjustment of the proton beam energy, flux density, irradiation time, and / or irradiation angle based on nuclear reaction monitoring results. Compared to open-loop irradiation based solely on a preset treatment plan, this invention facilitates closed-loop control based on in vivo nuclear reaction feedback information, thereby reducing the risk of insufficient nuclear reaction or excessive local reaction and improving the controllability and safety of the treatment process.

[0086] Fifth, this invention utilizes a proton beam to induce a nuclear reaction in nitrogen-15-labeled drugs enriched within the tumor lesion area. This allows the high linear energy transfer particles generated by the nuclear reaction to primarily act on the nitrogen-15-enriched region, which is beneficial for enhancing the local radiobiological effects of the tumor lesion area and reducing unnecessary impacts on normal tissues outside the target area, thereby improving the targeting of the treatment.

[0087] Sixth, the present invention provides a radiation shielding and safety interlocking system, including a shielding wall, a treatment room shielding layer, a local shielding component for the non-lesion area of ​​the patient, a beam transmission vacuum tube through-wall shielding sleeve, and a collimator connection end shielding cover. This system can provide comprehensive protection against direct proton beam radiation, scattered radiation, and secondary radiation, while also taking into account the usage requirements of collimator rotation, beam transmission, and patient positioning adjustment. This is beneficial to improving the system's radiation protection reliability and clinical adaptability.

[0088] In summary, this invention, through the synergistic combination of nitrogen-15 labeled drug targeted delivery, precise proton beam irradiation, in vivo nuclear reaction signal monitoring, feedback closed-loop regulation, and multi-layer radiation shielding structure, is beneficial to improving the targeting, controllability, safety, and implementation stability of proton nitrogen-15 nuclear reaction radiotherapy. Attached Figure Description

[0089] Figure 1 A schematic diagram of the proton beam precision irradiation device in one embodiment of the radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reaction provided by the present invention;

[0090] Combination Figure 1As shown, the proton beam is generated by a proton accelerator and regulated by an energy selection system before entering the beam transmission vacuum tube 11. The beam transmission vacuum tube 11 passes horizontally through the shielding wall 71 and transmits the proton beam to the rotatable proton beam collimator 12. The rotatable proton beam collimator 12 is mounted on one side of the shielding wall 71 via a gyroscopic support 2 and guides the collimated, precisely aligned proton beam 13 to the tumor lesion target area 92 within the patient's body.

[0091] Figure 2 This is a schematic diagram of the structure of the injection auxiliary component in the radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reaction provided by the present invention, when it is attached to the patient's body surface through the lesion.

[0092] Combination Figure 2 As shown, the nitrogen-15 labeled glutamine targeted drug delivery aid component is attached to the patient's body surface 91 via a lesion-adhesive fixation base 82. A medical adjustable positioning frame 81 is connected to the lesion-adhesive fixation base 82, and a three-dimensional micro-adjustment clamp 83 is used to hold the sterile injection syringe 62 and the disposable leak-proof injection needle 63. A medical micro-infusion pump 61 is used to inject the nitrogen-15 labeled glutamine preparation into the tumor lesion target area 92 or its adjacent area according to preset parameters.

[0093] Figure 3 This is a schematic diagram of the real-time nuclear reaction and dose monitoring system in one embodiment of the radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reaction provided by the present invention.

[0094] Combination Figure 3 As shown, the real-time nuclear reaction and dose monitoring system may include four detectors 51. The four detectors 51 are arranged circumferentially around the tumor lesion target area 92. Each detector 51 has a lead collimation sleeve 52 at its front end to define the detection direction and reduce background interference. The detectors 51 are used to acquire data with ¹ 5 N(p,α)¹²C nuclear reaction process 12 The gamma-ray signal generated by C de-excitation.

[0095] Figure 4 A side view of one embodiment of the radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reaction provided by the present invention;

[0096] Combination Figure 4 As shown, the patient is supported on a six-dimensional adjustable treatment bed 3. A beam transmission vacuum tube 11 passes through a shielding wall 71 and delivers the proton beam to a rotatable proton beam collimator 12. The precise proton beam 13 emitted from the rotatable proton beam collimator 12 is directed into the tumor lesion target area 92. A nitrogen-15 labeled glutamine targeted drug delivery aid is positioned above the patient's body surface 91 to assist in drug delivery. A detector 51 is positioned around the target area to collect nuclear reaction-related signals in real time.

[0097] Figure 5 This is a top view schematic diagram of a radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions provided by the present invention in one embodiment;

[0098] Combination Figure 5 As shown, the six-dimensional adjustable treatment bed 3 carries the patient and adjusts the tumor lesion target area 92 to the irradiation path of the precise proton beam 13. A shield 72 is located at the connection area between the rotatable proton beam collimator 12 and the shielding wall 71. Multiple detectors 51 are arranged circumferentially to collect gamma-ray signals from multiple directions. This arrangement facilitates the coordinated operation of proton beam irradiation, drug delivery, nuclear reaction monitoring, and radiation shielding.

[0099] Figure 6 A schematic diagram illustrating the relationship between proton energy and nitrogen-15-related nuclear reaction cross sections provided by this invention;

[0100] Combination Figure 6 As shown, Figure 6 This diagram illustrates the relationship between proton energy and the nitrogen-15-related nuclear reaction cross-section during system operation. This diagram can be used to help determine the proton beam energy setting range, ensuring the proton beam reaches the target area of ​​the tumor lesion within the preset reaction energy region. It should be noted that the actual proton beam energy used in treatment should also be determined considering patient tissue thickness, tumor depth, beam energy loss, and the treatment plan.

[0101] Figure 7 The results of an in vitro cell irradiation verification experiment for the radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reaction provided by this invention are shown in the figure.

[0102] Combination Figure 7 As shown, in an in vitro cell irradiation validation experiment, a control group without nitrogen-15 labeled glutamine was compared with experimental groups receiving different concentrations of nitrogen-15 labeled glutamine under proton irradiation. Under the same experimental conditions, the experimental groups receiving 500 μg / mL and 4000 μg / mL nitrogen-15 labeled glutamine showed lower cell viability compared to the control group. When cell viability decreased to 70% as the evaluation endpoint, under these experimental conditions, the required irradiation dose in the nitrogen-15 labeled glutamine group was lower than that in the untreated control group. These experimental results illustrate that the combined use of nitrogen-15 labeled glutamine and proton irradiation may enhance the cell damage effect, but do not constitute a limitation on clinical efficacy.

[0103] The reference numerals in the accompanying drawings include: 11-beam transmission vacuum tube, 12-rotatable proton beam collimator, 13-precision proton beam, 2-rotary support, 3-six-dimensional adjustable treatment bed, 51-detector, 52-lead collimation sleeve, 61-medical micro-injection pump, 62-sterile injection syringe, 63-disposable anti-leakage injection needle, 71-shielded wall, 72-shielded cover, 81-medical adjustable positioning frame, 82-lesion-fitting fixing base, 83-needle body three-dimensional fine-tuning clamp, 91-patient's body surface, 92-tumor lesion target area. Detailed Implementation

[0104] To make the objectives, technical solutions, and beneficial effects of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. The illustrative embodiments and descriptions of this invention are only for explaining the invention and are not intended to limit the invention:

[0105] It should be noted that "nitrogen-15" mentioned in this invention is a stable isotope. This invention provides a radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions. This system involves inducing a nitrogen-15 nuclear reaction through external proton beam irradiation after nitrogen-15-labeled drugs have accumulated in the tumor lesion area, thereby enhancing the local radiobiological effects of the tumor lesion area. The "real-time nuclear reaction and dose monitoring system" mentioned herein can be understood as a real-time nuclear reaction and dose monitoring system, which can be used to collect proton beam dose-related parameters and gamma-ray signals related to nuclear reactions. Figures 1 to 7 Specific embodiments thereof are shown.

[0106] like Figures 1 to 7 As shown, this embodiment provides a radiotherapy system based on real-time monitoring of proton nitrogen-15 induced nuclear reaction, including a proton beam precision irradiation device, a six-dimensional adjustable treatment bed 3, a nitrogen-15 labeled glutamine targeted drug delivery auxiliary component, a real-time nuclear reaction and dose monitoring system, and a radiation shielding and safety interlocking system.

[0107] Among them, the proton beam precision irradiation device is used to generate and modulate the precision proton beam 13 incident on the tumor lesion target area 92 in the patient's body, so that the precision proton beam 13 matches the area of ​​nitrogen-15 labeled glutamine preparation enriched in the tumor lesion target area 92, so as to induce¹ 5N(p,α)¹²C nuclear reaction; the six-dimensional adjustable treatment bed 3 is set within the irradiation range of the proton beam precision irradiation device to support the patient and adjust the patient's position; the nitrogen-15 labeled glutamine targeted drug delivery auxiliary component is used to achieve quantitative and targeted drug delivery of nitrogen-15 labeled glutamine preparations to the tumor lesion target area 92 or its adjacent area; the real-time nuclear reaction and dose monitoring system is communicatively connected to the proton beam precision irradiation device and the nitrogen-15 labeled glutamine targeted drug delivery auxiliary component, respectively, to monitor the proton beam dose parameters in real time and with ¹²C. 5 The system detects N(p,α)¹²C-related gamma-ray signals and sends feedback control signals to the proton beam precision irradiation device based on the monitoring results. The radiation shielding and safety interlocking system is used to comprehensively shield the mixed radiation field formed by direct proton beam radiation, scattered radiation, and secondary radiation.

[0108] The working process of this embodiment may include steps such as drug administration preparation, patient positioning, proton beam irradiation, nuclear reaction signal monitoring, and feedback regulation. First, the location, morphology, and depth of the tumor lesion target area 92 are determined based on patient imaging data, and the drug administration parameters and proton beam irradiation parameters for the nitrogen-15 labeled glutamine preparation are formulated accordingly. Subsequently, the quantitative and targeted drug administration of the preparation is completed using a nitrogen-15 labeled glutamine targeted drug administration auxiliary component. After drug administration, the patient lies supine on a six-dimensional adjustable treatment bed 3, and the patient's position is adjusted using the six-dimensional adjustable treatment bed 3 to align the tumor lesion target area 92 with the irradiation area of ​​the precise proton beam 13. During treatment, the proton beam precision irradiation device outputs a precise proton beam 13 to the tumor lesion target area 92, and the real-time nuclear reaction and dose monitoring system simultaneously collects proton beam dose parameters and gamma-ray signals, and performs feedback adjustment on the proton beam energy, flux density, irradiation time, and / or irradiation angle based on the collection results.

[0109] It should be noted that the drug administration time, drug dosage, irradiation energy, irradiation flux and irradiation time in the above-mentioned process can be set according to the location, depth and volume of the tumor lesion, the individual condition of the patient and the treatment plan. This embodiment does not limit the specific clinical prescription parameters.

[0110] I. Proton Beam Precision Irradiation Facility

[0111] like Figure 1 As shown, in one embodiment, the proton beam precision irradiation device includes a proton accelerator, an energy selection system, a beam transport vacuum tube 11, a beam parameter control component, and a rotatable proton beam collimator 12.

[0112] The proton accelerator can be a cyclotron or a synchrotron, used to generate a proton beam for therapeutic use. In one embodiment, the proton beam energy range output by the proton accelerator can be 70~200MeV. An energy selection system is disposed at the beam extraction end of the proton accelerator and is used to select the proton beam energy according to the depth of the tumor lesion target region 92 and the treatment plan, so that the proton beam has a preset energy distribution when it reaches the tumor lesion target region 92, thereby generating a proton beam within the preset energy range.

[0113] The beam transmission vacuum tube 11 passes horizontally through the shielding wall 71, with one end connected to the energy selection system and the other end connected to the rotatable proton beam collimator 12. The beam transmission vacuum tube 11, passing horizontally through the shielding wall 71, provides a low-scattering transmission channel for the proton beam. Depending on the treatment room layout requirements, the beam transmission vacuum tube 11 can also be equipped with a diode deflection magnet, a quadrupole focusing magnet, a beam monitor, or a beam gate to achieve beam deflection, focusing, position monitoring, and rapid shutdown.

[0114] The beam parameter control component is electrically connected to the proton accelerator, the energy selection system, and the real-time nuclear reaction and dose monitoring system, respectively. The beam parameter control component may include an energy regulation module, a flux regulation module, and a beam shutdown module. The energy regulation module is used to regulate the proton beam energy; the flux regulation module is used to regulate the proton beam intensity or flux density; the beam shutdown module is used to cut off the proton beam output when the monitoring result exceeds a preset safety threshold, the treatment room interlock status is abnormal, or the detector status is abnormal. The proton beam flux density adjustment range of the flux regulation module can be set according to the treatment plan, for example, 10. 8 ~10¹ 0 cm⁻²·s⁻¹, but this numerical range does not constitute a limitation on the scope of protection of this invention.

[0115] A rotatable proton beam collimator 12 is rotatably mounted on one side of the shielding wall 71 via a swivel support 2. The inner ring of the swivel support 2 is fixedly connected to the shielding wall 71, and the outer ring is fixedly connected to the rotatable proton beam collimator 12. The rotatable proton beam collimator 12 can rotate around a preset rotation axis to adjust the incident angle of the precise proton beam 13. The rotation range of the rotatable proton beam collimator 12 can be 0~360°, and the range of the proton beam incident angle can also be preset according to the treatment room space and treatment needs.

[0116] The rotatable proton beam collimator 12 has an internal collimation channel for the proton beam to pass through. This collimation channel can be a conical channel. The body of the rotatable proton beam collimator 12 is made of a composite material of lead and zirconium boride, which fully utilizes the attenuation ability of lead to high-energy photon scattering and the synergistic shielding effect of zirconium boride to moderate neutron absorption. It has an internally machined conical hollow channel, the geometry of which determines the cross-sectional shape and divergence angle of the emitted proton beam. Crucially, a boron-containing neutron absorption layer is deposited on the inner wall of the conical hollow channel. This absorption layer can effectively capture and absorb stray neutrons generated by scattering and nuclear reactions on the inner wall of the channel, as well as non-collimated scattered protons at the beam edge.

[0117] Through the above structure, the proton beam precision irradiation device can adjust the proton beam energy, beam intensity and incident angle according to the treatment plan, so that the precision proton beam 13 can achieve a good spatial match with the nitrogen-15 enriched region in the tumor lesion target area 92, and provide a hardware foundation for subsequent feedback control based on monitoring signals.

[0118] II. Six-position adjustable treatment bed

[0119] like Figure 4 and Figure 5 As shown, the six-dimensional adjustable treatment bed 3 is used to support and adjust the patient's position. The six-dimensional adjustable treatment bed 3 may include a bed frame, a lifting assembly, a horizontal movement assembly, a rotation assembly, and a position fixing assembly;

[0120] The six-dimensional adjustable treatment bed 3 can achieve three-dimensional movement of the bed body up and down, left and right, and forward and backward, as well as three-dimensional rotation around the X / Y / Z axes, with a positioning accuracy of ±0.05mm; the body position fixation component includes a malleable soft pad and a medical fixation strap to fix the patient's body position; the six-dimensional adjustable treatment bed 3 is linked with a real-time nuclear reaction and dose monitoring system to correct the patient's body position deviation based on image positioning data and / or monitoring data during the treatment process.

[0121] This treatment bed has six degrees of freedom of motion, enabling three-dimensional translational movements of the bed body in the up, down, left, right, and forward and backward directions, as well as three-dimensional rotational movements around the X, Y, and Z axes, with a positioning accuracy of ±0.05mm.

[0122] The positioning fixation component includes one or more of the following: a malleable soft pad, a thermoplastic film, a medical fixation strap, a head, neck and shoulder fixation frame, and a trunk positioning frame. The positioning fixation component is used to fix the patient's position and reduce the positional deviation caused by the patient's movement, breathing movements or muscle relaxation during treatment.

[0123] The six-dimensional adjustable treatment bed 3 can communicate with a real-time nuclear reaction and dose monitoring system. When image positioning data indicates a deviation between the patient's actual position and the preset position, the six-dimensional adjustable treatment bed 3 can automatically or semi-automatically correct itself according to control commands. In one embodiment, when the real-time nuclear reaction and dose monitoring system detects a deviation between the gamma-ray signal distribution and the expected signal distribution, it can also send a prompt signal or correction signal to the six-dimensional adjustable treatment bed 3 to assist in correcting the patient's position.

[0124] Based on the same inventive concept, the six-dimensional adjustable treatment bed 3 has several alternative embodiments. For example, in terms of the driving method, this embodiment preferably uses a servo motor-driven mechanical transmission scheme to achieve high-precision positioning of ±0.05mm. However, in scenarios with slightly lower precision requirements, hydraulic or pneumatic lifting and translation mechanisms can also be used. Regarding body positioning, in addition to the combination of a malleable soft pad and medical fixation straps, vacuum negative pressure molding pads, thermoplastic film fixation masks, or three-dimensional positioning frames can be selected depending on the treatment site. Regarding body positioning correction, in addition to fully automatic linkage with a real-time nuclear reaction and dose monitoring system, a semi-automatic mode with manual fine-tuning and audio-visual prompts can also be used, allowing operators to remotely correct the position outside the treatment room based on the prompts. Regarding image guidance, in addition to X-ray or CT imaging systems, radiation-free real-time positioning methods such as ultrasound imaging or optical surface tracking systems can also be integrated.

[0125] III. Nitrogen-15 labeled glutamine targeted drug delivery aid component

[0126] like Figure 2 , Figure 4 and Figure 5 As shown, the nitrogen-15 labeled glutamine targeted drug delivery aid component includes a micro-precision injection unit, a targeted positioning and fixation unit, a drug isothermal storage unit, and a drug delivery parameter control unit.

[0127] A micro-injection precision unit is used to inject nitrogen-15 labeled glutamine preparations into the tumor lesion area or its adjacent area at a preset injection rate and preset injection dose. It includes a medical micro-injection pump 61, a sterile injection syringe 62, and a disposable anti-leakage injection needle 63. The medical micro-injection pump 61 is used to inject the nitrogen-15 labeled glutamine preparations into the tumor lesion target area 92 or its adjacent area at a preset injection rate and preset injection dose. The medical micro-injection pump 61 can be a plunger-type injection pump or a peristaltic injection pump. In one embodiment, the injection rate of the medical micro-injection pump 61 is adjustable from 0.1 mL / h to 10 mL / h, and the dose control accuracy is ±0.01 mL. The disposable anti-leakage injection needle 63 can include a needle tube and a needle hub. The sidewall of the needle tube can be provided with at least one dispensing hole, and the needle hub can be provided with a sealing structure to reduce the risk of backflow or leakage of the drug solution during injection.

[0128] The disposable anti-leakage injection needle includes a needle tube and a needle hub. The needle tube has a micro-sized drug dispensing hole on its sidewall, and the needle hub has an anti-leakage sealing ring to reduce the risk of drug backflow or leakage during injection. The disposable injection needle is used to deliver nitrogen-15 labeled glutamine preparations at a set flow rate and dose. Preferably, the injection rate of the medical micro-infusion pump is adjustable from 0.1 mL / h to 10 mL / h, with a dose control error of no more than ±1%. If higher-precision actual test data is available, it can be further limited to ±0.01 mL or other specific values.

[0129] The targeted positioning and fixation unit is used to position and fix the injection needle, and includes a medical adjustable positioning frame 81, a lesion-adhesive fixation base 82, and a needle body three-dimensional fine-tuning clamp 83. The lesion-adhesive fixation base 82 is used to conform to the patient's body surface 91 and provide a positioning reference. The medical adjustable positioning frame 81 is connected to the lesion-adhesive fixation base 82 and is used to support the needle body three-dimensional fine-tuning clamp 83. The needle body three-dimensional fine-tuning clamp 83 is used to adjust the position of the injection needle in the X, Y, and Z directions, enabling micron-level fine-tuning in the X / Y / Z three axes to accommodate injection needles of different diameters (such as clamping disposable anti-leakage injection needles 63). In one embodiment, the adjustment accuracy of the needle body three-dimensional fine-tuning clamp 83 can be ±0.05 mm. The lesion-adhesive fixation base 82 can be made of medical flexible silicone, thermoplastic material, or malleable composite material, and can have embedded shaped metal wires inside to balance body surface conformation and structural stability.

[0130] A drug thermostatic storage unit is used to preserve nitrogen-15 labeled glutamine formulations within a preset temperature range. In one embodiment, the storage temperature of the drug thermostatic storage unit is 2–8°C to meet the storage requirements of the formulation before use.

[0131] The drug administration parameter control unit is connected to the medical micro-infusion pump 61 and is used to set and control the injection speed, injection dose, and injection time. The drug administration parameter control unit may include a data processor, a communication module, a remote control terminal, and an alarm module. The data processor stores patient drug administration parameters and controls the injection speed, injection dose, and injection time. It triggers an alarm and automatically corrects the system when the actual parameters deviate from the set parameters by more than ±0.1%. The communication module enables data transmission between the data processor and the remote control terminal. The remote control terminal allows for remote control of the medical micro-infusion pump 61 from outside the treatment room. The alarm module issues an alarm signal and pauses the injection or prompts the operator to make corrections when the actual injection speed, actual injection dose, needle position, or drug storage temperature exceeds a preset threshold.

[0132] During drug administration, the operator can determine the preset injection target point based on the patient's imaging data, attach the lesion-adhesive fixing base 82 to the patient's body surface 91, and adjust the position and angle of the disposable anti-leakage injection needle 63 using the medical adjustable positioning frame 81 and the needle body three-dimensional micro-adjustment clamp 83. After positioning, the medical micro-infusion pump 61 injects the nitrogen-15 labeled glutamine preparation according to preset parameters. The drug administration parameter control unit records and monitors the drug administration data in real time to improve the controllability and traceability of the drug administration process.

[0133] IV. Real-time nuclear reaction and dose monitoring system

[0134] like Figures 3 to 5 As shown, the real-time nuclear reaction and dose monitoring system includes a gamma-ray nuclear reaction monitoring unit, a proton beam dose monitoring unit, a data processing module, and a feedback control module. The gamma-ray nuclear reaction monitoring unit is used to capture¹ 5 The characteristic gamma rays (4.4 MeV) generated during the N(p,α)¹²C nuclear reaction, produced by ¹²C deexcitation, are used to monitor the nuclear reaction process in situ. A proton beam dose monitoring unit is used to acquire proton beam dose rate, beam intensity, beam spot position, and / or irradiation time. A data processing module is used to calculate the nuclear reaction rate based on the detection data from the gamma-ray nuclear reaction monitoring unit; a feedback control module, electrically connected to the beam parameter control component in the proton beam precision irradiation device, is used to send control signals based on the calculation results.

[0135] It should be noted that during actual detection, the gamma signal energy spectrum may be affected by factors such as tissue attenuation, scattering, background radiation, detector resolution, and collimation conditions. Therefore, the data processing module can perform energy window filtering, background subtraction, and attenuation correction on the acquired signal.

[0136] The gamma-ray nuclear reaction monitoring unit may include multiple gamma-ray detectors 51. The multiple gamma-ray detectors 51 may be arranged around the treatment bed, on the walls of the treatment room, around the collimator, or on the outer side of the patient's lesion area to collect gamma-ray signals from different directions.

[0137] In one implementation, such as Figure 3 As shown, the treatment room includes four gamma-ray detectors 51 arranged in a ring array around the tumor target area at a distance of 100 cm. Each gamma-ray detector 51 is a NaI(Tl) scintillator detector with an energy response range of 0.5–10 MeV, a detection efficiency greater than 20% for gamma rays in the 4.4 MeV energy range, and a response time ≤10 ms. Each gamma-ray detector 51 is equipped with a lead collimating sleeve 52 and fixed by an adjustable bracket with an installation accuracy of ±1 cm. The adjustable bracket allows for height, horizontal angle, and pitch angle adjustments to orient the gamma-ray detector 51 toward the tumor target area 92.

[0138] In this embodiment, the gamma-ray nuclear reaction monitoring unit adopts a distributed ring array layout. Four gamma-ray detectors 51 are evenly arranged around the periphery of the treatment room at a distance of 100cm from the tumor lesion target area, forming a comprehensive three-dimensional monitoring of the area where the nuclear reaction occurs in the patient's body. Each gamma-ray detector 51 is a NaI(Tl) scintillator detector, with an energy response range covering 0.5–10 MeV. It has a detection efficiency of more than 20% for the characteristic gamma rays in the 4.4 MeV energy range generated by ¹²C deexcitation, and a response time of no more than 10ms. Each gamma-ray detector 51 is equipped with a lead collimating sleeve 52 at its front end to limit the incident solid angle of the gamma rays and shield scattered gamma rays from non-lesion directions and ambient background radiation. The detectors 51 are fixed to the wall or floor of the treatment room by adjustable height brackets, with the installation accuracy controlled within ±1cm.

[0139] Four gamma-ray detectors 51 are evenly distributed circumferentially, ensuring that at least one gamma-ray detector 51 is within the effective detection solid angle coverage area regardless of whether the nuclear reaction occurs in different locations within the patient's body, such as the head, chest, or abdomen. Compared to single detectors or planar arrays, this distributed layout effectively avoids signal loss due to patient body shape obstruction or special lesion locations, ensuring comprehensive real-time perception of the nuclear reaction process. The NaI(Tl) scintillator detector has the advantages of low cost and small size, making it suitable for multi-point distributed deployment in the limited space of the treatment room; its energy response range of 0.5–10 MeV fully covers the detection requirements of gamma rays in the 4.4 MeV energy region, while the detection efficiency of more than 20% ensures that sufficient counting statistics can be obtained even at low nuclear reaction rates; the fast response time of no more than 10 ms meets the strict requirement of no delay in data feedback for real-time monitoring, ensuring the timeliness of closed-loop control. By limiting the incident solid angle of gamma rays, the lead collimating sleeve 52 effectively shields against interference from scattered gamma rays from non-lesion areas within the patient's body and background radiation from the treatment room environment. This ensures that the gamma ray detector 51 receives gamma ray signals only from the collimation direction, i.e., the direction of the target area of ​​the lesion, thereby significantly improving the extraction accuracy and reliability of characteristic gamma ray signals and providing a high-quality data foundation for the accurate calculation of subsequent nuclear reaction rates. Fourthly, the adjustable bracket, combined with an installation accuracy of ±1cm, gives the monitoring system a high degree of clinical adaptability. Medical staff can flexibly adjust the height and orientation of each gamma ray detector 51 according to the patient's height, lesion location, and treatment position, ensuring that the collimation direction of the gamma ray detector 51 is always aligned with the target area where the nuclear reaction occurs, meeting the personalized monitoring needs of patients with different body parts and body types.

[0140] In one embodiment, the data processing module is configured to: acquire the count rate of characteristic gamma rays in the 4.4 MeV energy region measured by the gamma-ray nuclear reaction monitoring unit, and process the count rate according to the nuclear physics formula Rreaction = Nreaction γ / (ε·Ω·P), converting the count rate into the body's ¹ 5 N(p,α)¹²C nuclear reaction rate Rreaction, where Ω is the absolute detection efficiency of detector 51, P is the solid angle of detector 51 to the reaction source, and P is the branching ratio of characteristic γ-rays in the 4.4 MeV energy region emitted during the ¹²C de-excitation process.

[0141] The data processing module acquires in real time the characteristic gamma-ray count rate N in the 4.4 MeV energy range measured by the gamma-ray nuclear reaction monitoring unit. γ The count rate is the effective count of 4.4 MeV energy region characteristic gamma rays extracted from the original signal of detector 51 after energy discrimination and noise reduction processing, belonging only to the 4.4 MeV energy region characteristic gamma rays generated by ¹²C de-excitation. Subsequently, the data processing module calls pre-calibrated and stored physical parameters, including the absolute detection efficiency ε of detector 51 for 4.4 MeV energy region characteristic gamma rays, the geometric solid angle Ω of the collimating sleeve of detector 51 to the nuclear reaction source in the patient's body, and the branch ratio P of the path that completes de-excitation by emitting 4.4 MeV energy region characteristic gamma rays during ¹²C de-excitation. Based on this, the data processing module uses the nuclear physics quantitative relationship formula R (reaction) = N γ / (ε·Ω·P) is used for real-time calculations to convert the measured characteristic gamma-ray count rate into the number of rays generated per unit time in the body¹ 5 The number of N(p,α)¹²C nuclear reactions, also known as the nuclear reaction rate R (reaction), directly reflects the actual yield of α particles during treatment, providing the most direct quantitative indicator for assessing the intensity of nuclear reaction therapy.

[0142] This data processing module scientifically restores the raw count rate received by the gamma-ray detector 51 to the actual number of nuclear reactions occurring in vivo by accurately describing the geometric detection conditions through the solid angle Ω, quantitatively characterizing the response capability of the gamma-ray detector 51 through the absolute detection efficiency ε, and accurately introducing the branching ratio P to the probability of nuclear reaction de-excitation pathways. This elevates the evaluation of treatment effect from "indirect speculation" to "direct quantification." The feedback control module requires a clear numerical indicator as the benchmark for control judgment. The nuclear reaction rate R (reaction) output by this data processing module is precisely such a quantitative parameter with clear physical meaning and clinical value. When R (reaction) deviates from the pre-planned target range, the feedback control module can accurately determine the direction and magnitude of adjustment needed, thereby avoiding over-regulation or under-regulation that may result from regulation based solely on experience or indirect estimation. The nuclear physics formula used in this module is concise, and all parameters can be pre-calibrated and stored. In actual operation, only the real-time measured count rate Nγ needs to be substituted to quickly output the nuclear reaction rate result, ensuring that the entire closed-loop link delay from signal acquisition to the issuance of feedback control commands remains within an acceptable range.

[0143] In one embodiment, the feedback control module is configured to: compare the calculated nuclear reaction rate with a preset target value; and when the nuclear reaction rate deviates from the target value, automatically send a control signal to the beam parameter control component to adjust the energy and / or flux density of the proton beam, thereby achieving real-time closed-loop control of the proton beam parameters.

[0144] The feedback control module receives the real-time calculation result of the nuclear reaction rate R (reaction) from the data processing module. Subsequently, this module compares the calculated actual nuclear reaction rate with the preset target value set during the preoperative planning stage. This preset target value is a safe and effective range for the nuclear reaction rate, determined comprehensively based on factors such as tumor lesion volume, nitrogen-15 nuclide enrichment concentration, and treatment plan. When the comparison result shows that the actual nuclear reaction rate is within the normal range of the preset target value, the feedback control module maintains the current control signal unchanged, and the proton beam parameters remain stable. When the actual nuclear reaction rate deviates from the target value—that is, below the lower limit of the target range indicating insufficient nuclear reaction and poor treatment effect, or above the upper limit of the target range indicating excessive nuclear reaction and risk of damage to normal tissue—the feedback control module automatically generates and sends a control signal to the beam parameter control component. This control signal instructs the beam parameter control component to adjust the energy and / or flux density of the proton beam accordingly: if the nuclear reaction rate is too low, the proton beam flux density is increased or the proton beam energy is optimized to approach the peak value of the nuclear reaction cross-section; if the nuclear reaction rate is too high, the flux density is reduced or irradiation is paused. Through the above-mentioned cycle of "real-time comparison - deviation judgment - automatic command - parameter adjustment - effect re-monitoring", the real-time closed-loop control of proton beam parameters is realized, ensuring that the internal reaction in the body is always maintained within the preset safe and effective range throughout the entire treatment process.

[0145] This feedback control module uses the nuclear reaction rate, a parameter directly reflecting treatment efficacy, as the basis for regulation. This imbues the treatment process with intelligent characteristics of "self-awareness" and "self-regulation," proactively adapting to various deviations that may occur during treatment and ensuring consistent therapeutic effects. Excessive nuclear reaction may cause alpha particle production to exceed the tumor target area, resulting in accidental damage to adjacent normal tissues. This feedback control module sets a safety upper limit; when the nuclear reaction rate reaches a warning threshold, it automatically reduces beam flux or pauses irradiation, eliminating the continuous accumulation of risks from excessive nuclear reaction at the engineering control level and providing reliable safety for patients. By automatically maintaining the nuclear reaction rate within the preset target range, it avoids incomplete treatment requiring additional irradiation due to insufficient reaction, and also prevents the passive situation of forced treatment interruption or reduced efficiency due to excessive reaction, ensuring that each treatment is completed efficiently and at its optimal state.

[0146] This invention addresses the core principle of proton nitrogen therapy: external proton beam irradiation triggers intravenous stimulation within the patient.¹ 5 The N(p,α)¹²C nuclear reaction innovatively incorporates a real-time dose monitoring module. This module abandons the traditional proton beam monitoring mode and instead captures the characteristic gamma rays generated by the de-excitation of excited state¹²C during the nuclear reaction. This enables real-time, non-invasive assessment of the amount of nuclear reaction occurring in vivo, providing a direct basis for closed-loop regulation of proton beam irradiation parameters and ensuring a dual balance between nuclear reaction efficiency and treatment safety.

[0147] The real-time dose monitoring module includes a gamma-ray detection unit, a data calculation and analysis unit, and a closed-loop control unit. The gamma-ray detection units are distributed across key locations within the treatment room. The data calculation and analysis unit uses nuclear physics formulas to quantitatively convert gamma-ray counts into nuclear reaction numbers. The closed-loop control unit dynamically adjusts the proton beam parameters based on the conversion results. The structure, principle, parameters, and collaborative working logic of each unit are as follows:

[0148] 1. Gamma-ray detection unit

[0149] The core design of this unit is a long-range distributed gamma-ray detector array, targeting¹ 5 The 4.4 MeV characteristic gamma rays generated by ¹²C deexcitation in the N(p,α)¹²C nuclear reaction were precisely detected. The specific nuclear reaction equation and device design are as follows:

[0150] ;

[0151] The specific nuclear reaction pathway is as follows: after a proton (p) bombards a nitrogen-15 target nucleus, a complex nucleus is first formed. 16O*, then the composite nucleus decays through the (p,α) channel, emitting a high-LET (linear energy transfer) α particle and generating ¹²C* in the first excited state. This excited ¹²C* de-excites to the ground state within a short time, instantaneously releasing a characteristic gamma ray with an energy of approximately 4.4 MeV during this transition. This characteristic gamma ray has a strict co-occurrence with the generation of the α particle;

[0152] (1) Detector selection and layout

[0153] Detector type: NaI(Tl) scintillator detectors are selected, which are low in cost, high in detection efficiency, and small in size, making them suitable for distributed layout in treatment rooms;

[0154] Layout and location: Four detector units are arranged around the treatment room at a distance of 100cm from the tumor lesion target area to form a ring-shaped longitudinal monitoring array. The center is located in the patient's treatment center, covering areas where the patient's whole-body nuclear reaction may occur (lesion areas such as the head, chest, and abdomen), avoiding monitoring blind spots.

[0155] Each detector unit is equipped with a lead collimation sleeve to limit the solid angle of gamma ray incident, reduce interference from ambient scattered gamma rays, and improve the signal-to-noise ratio.

[0156] Installation method: The detector unit is fixed to the wall or floor of the treatment room by an adjustable height medical bracket. The bracket has horizontal rotation and pitch adjustment functions, and the orientation of the detector can be adjusted according to the patient's height and lesion location to ensure that the gamma ray detection direction is perpendicular to the target area of ​​the patient's internal reaction or the patient's tumor area, with an installation accuracy of ±1cm.

[0157] (2) Technical parameters

[0158] Energy response range: 0.5–10 MeV, covering the gamma-ray detection requirements in the 4.4 MeV energy region;

[0159] Detection efficiency for γ-rays in the 4.4 MeV energy range: greater than 20%;

[0160] Energy resolution: NaI(Tl) detector ≤8% (for 662keV γ-rays) ensures effective differentiation of characteristic γ-rays from background radiation;

[0161] Linear counting range: 0 to 10 6 counts / s, adapted for gamma-ray counting monitoring under different intensities of nuclear reactions;

[0162] Response time: ≤10ms, meeting the time requirements for real-time monitoring and ensuring no delay in data feedback.

[0163] 2. Data Calculation and Analysis Unit

[0164] The core function of this unit is to convert the 4.4 MeV energy range gamma-ray count rate collected by the detector into the number of gamma rays per unit time in the patient's body using a nuclear physics quantitative formula.¹ 5 The number of N(p,α)¹²C nuclear reactions was measured, and the efficiency of the nuclear reactions was evaluated in conjunction with clinical dosage guidelines, providing a quantitative basis for closed-loop regulation.

[0165] (1) Definition of core physical formulas and parameters

[0166] Based on the solid angle counting principle of gamma-ray detection, the gamma-ray count rate measured by the detector With the body's core reaction rate (per unit of time¹) 5 The relationship between the number of N(p,α)¹²C nuclear reactions, in s⁻¹, is:

[0167] N γ =R 反应 ·(ε·Ω·P;

[0168] The parameters are defined as follows:

[0169] The detector measured the characteristic gamma-ray count rate (counts / s) in the 4.4 MeV energy region, which was acquired in real time by the gamma-ray detection unit.

[0170] : in the body¹ 5 The N(p,α)¹²C nuclear reaction rate (s⁻¹) is the parameter to be solved, which directly reflects the amount of nuclear reaction that occurs.

[0171] The absolute detection efficiency (dimensionless) of the detector for 4.43 MeV gamma rays is calibrated by the manufacturer.

[0172] The solid angle (sphericity) of the detector to the internal reaction source of the patient's body is determined by the spatial relationship between the detector's layout and the patient's lesion area;

[0173] : Gamma-ray emission probability (dimensionless), refers to the branching ratio of 4.43 MeV gamma rays emitted during the de-excitation of ¹²C, which is a known fixed parameter.

[0174] (2) Solid angle Calculation method

[0175] Solid angle The "visible range" of the detector for nuclear reaction sources in the patient's body is described using a point source approximation (the lesion volume is much smaller than the detection distance):

[0176] ;

[0177] in:

[0178] Effective incident area of ​​the collimating sleeve of the detector (m²). , The collimation inlet radius;

[0179] : The straight-line distance (m) between the collimated entrance of the detector and the internal reaction point source of the patient's body.

[0180] Fixed layout parameters in this invention:

[0181] Example calculation:

[0182] Take the collimation inlet radius ,

[0183] Effective area:

[0184] ;

[0185] Solid angle of a single detector:

[0186] ;

[0187] If four ring detectors are deployed, the total solid angle is:

[0188] ;

[0189] (3) Nuclear reaction rate R 反应 Solving

[0190] Substituting the known parameters into the core formula, we can solve for the actual nuclear reaction rate in vivo:

[0191] R 反应 =N γ / (ε·Ω·P;

[0192] (4) Physical meaning of measurement data

[0193] 1. Directly corresponds to the intensity of the nucleus reaction.

[0194] The larger the value, the more likely it is to occur per unit time¹ 5 The more N(p,α)¹²C reactions there are, the higher the yield of α particles and the higher the efficiency of tumor cell killing.

[0195] Too low a level indicates insufficient nuclear response and inadequate treatment dosage.

[0196] 2. Correspondence with proton beam parameters

[0197] The energy and flux of the proton beam directly determine :

[0198] Below the target value → the proton beam flux is too low or the energy has not reached the reaction threshold energy, and needs to be increased;

[0199] Exceeding the safety threshold → The nuclear reaction is too strong and may damage normal tissue; it needs to be lowered.

[0200] (5) Data processing flow

[0201] 1. Real-time data acquisition by the detector The data is then transmitted to the data processing and analysis unit.

[0202] 2. The embedded processor performs signal noise reduction, energy calibration, and extracts effective counts of characteristic gamma rays in the 4.4 MeV energy region;

[0203] 3. Substitute , , Calculations yielded ;

[0204] 4. In conjunction with preoperative planning The comparison generates quantitative evaluation and visualization curves, which are then output to the control system.

[0205] The feedback control module is connected to the beam parameter control component and is used to generate a feedback control signal based on the nuclear reaction rate or relative intensity distribution of nuclear reactions output by the data processing module. The feedback control module can compare the estimated nuclear reaction rate with a preset target range. When the nuclear reaction rate is lower than the preset lower limit, the feedback control module can send an enhanced irradiation signal to the beam parameter control component to increase the proton beam flux density, extend the irradiation time, or adjust the proton beam energy; when the nuclear reaction rate is higher than the preset upper limit, the feedback control module can send an suppressed irradiation signal to the beam parameter control component to reduce the proton beam flux density, shorten the irradiation time, adjust the irradiation angle, or cut off the proton beam output.

[0206] Through the aforementioned real-time nuclear reaction and dose monitoring system, this embodiment can further obtain feedback information reflecting the nuclear reaction process in the bulk based on proton beam dose monitoring, thereby providing a basis for closed-loop control of proton beam parameters.

[0207] V. Radiation Shielding and Safety Interlocking System

[0208] like Figure 1 , Figure 4 and Figure 5As shown, the radiation shielding and safety interlocking system includes a shielding wall 71, a treatment room shielding layer, a local shielding component for the non-lesion area of ​​the patient, a through-wall shielding sleeve for the beam transmission vacuum tube 11, and a shielding cover 72 for the rotatable collimator connection end.

[0209] A shielding wall 71 is constructed to form a treatment room, providing basic shielding against the external environment. The shielding wall 71 can be formed using ordinary concrete, heavy concrete, boron-containing concrete, tungsten-containing concrete, lead plates, steel plates, or combinations thereof. In one embodiment, the shielding wall 71 can be a composite concrete wall with 5% boron powder and 3% tungsten powder added internally, and its thickness can be determined based on the maximum proton beam energy, the treatment room layout, and radiation protection evaluation results, for example, greater than 200 cm.

[0210] A shielding layer for the treatment room can be installed on the walls, floor, and / or ceiling to reduce the leakage of scattered and secondary radiation. The shielding layer may include one or more of a neutron moderator layer, a neutron absorber layer, and a gamma-ray shielding layer. The neutron moderator layer may include a polyethylene layer; the neutron absorber layer may include a boron-containing polyethylene layer; and the gamma-ray shielding layer may include a lead layer, a tungsten layer, a steel plate layer, or a heavy concrete layer. In one embodiment, the shielding layer uses an 8cm–10cm thick boron-containing polyethylene board, but its specific thickness and installation area should be determined according to radiation protection design requirements, such as fully covering the walls, floor, and ceiling of the treatment room to shield scattered protons.

[0211] The local shielding component for non-lesion areas can be a malleable shielding element, designed to conform to the non-lesion area of ​​the patient's body surface 91 according to the location of the lesion, thereby reducing the risk of the non-lesion area being affected by scattered radiation. This local shielding component can be made of boron-containing flexible materials, lead rubber, tungsten rubber, tungsten-containing composite materials, or combinations thereof.

[0212] A wall-penetrating shielding sleeve for the beam transmission vacuum tube 11 is disposed at the location where the beam transmission vacuum tube 11 passes through the shielding wall 71, to reduce the risk of leakage at the wall-penetrating channel. The wall-penetrating shielding sleeve can be formed of a boron-containing polyethylene layer, a lead layer, a steel layer, or a composite layer thereof. In one embodiment, the wall-penetrating shielding sleeve is a composite structure formed of two layers of boron-containing polyethylene and lead.

[0213] A shield 72 is disposed in the connection area between the rotatable proton beam collimator 12 and the shielding wall 71 or fixed support structure. The shield 72 can rotate coaxially with the rotatable proton beam collimator 12 to reduce the risk of leakage due to mechanical gaps in the connection area. In one embodiment, the shield 72 includes a stainless steel shell and a boron-containing polyethylene layer disposed inside the stainless steel shell.

[0214] The entrance to the treatment room may be equipped with a shielded door, which may include a lead layer, a steel structure layer, a boron-containing polyethylene layer, or a combination thereof. The shielded door may be equipped with a radiation interlock device. This radiation interlock device is used to prevent proton beam output or trigger beam shutdown when the shielded door is not closed, the dose rate inside the treatment room exceeds a preset threshold, or personnel accidentally enter the treatment room.

[0215] Through the aforementioned multi-layered shielding structure, the radiation shielding and safety interlocking system can be adapted to the radiation protection needs of different locations such as proton beam transmission, collimator rotation, patient irradiation, and treatment room entrance, which helps to improve the system's radiation protection reliability and clinical applicability.

[0216] Combination Figure 6 As shown, Figure 6 This diagram illustrates the relationship between proton energy and the nitrogen-15-related nuclear reaction cross-section during system operation. This diagram can be used to help determine the proton beam energy setting range, ensuring the proton beam reaches the target area of ​​the tumor lesion within the preset reaction energy region. It should be noted that the actual proton beam energy used in treatment should also be determined considering patient tissue thickness, tumor depth, beam energy loss, and the treatment plan.

[0217] Combination Figure 7 As shown, in an in vitro cell irradiation validation experiment, a control group without nitrogen-15 labeled glutamine was compared with experimental groups receiving different concentrations of nitrogen-15 labeled glutamine under proton irradiation. Under the same experimental conditions, the experimental groups receiving 500 μg / mL and 4000 μg / mL nitrogen-15 labeled glutamine showed lower cell viability compared to the control group. When cell viability decreased to 70% as the evaluation endpoint, under these experimental conditions, the required irradiation dose in the nitrogen-15 labeled glutamine group was lower than that in the untreated control group. These experimental results illustrate that the combined use of nitrogen-15 labeled glutamine and proton irradiation may enhance the cell damage effect, but do not constitute a limitation on clinical efficacy.

[0218] The above specific embodiments further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above are merely specific embodiments of the present invention and are not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions, characterized in that, The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reaction is configured to be used in conjunction with a nitrogen-15 labeled preparation to collect accompanying gamma-ray signals related to proton-induced nitrogen-15 nuclear reaction when the proton beam irradiates a predetermined target area, and to perform feedback regulation of proton beam parameters based on the accompanying gamma-ray signals. The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions includes: A proton beam precision irradiation device, rotatably mounted on the shielding wall of a radiation shielding and safety interlocking system, is used to generate a proton beam precisely incident on the tumor lesion area where nitrogen-15 accumulates within the human body. This allows the proton beam to spatially match the nitrogen-15-enriched labeled drug within the tumor lesion area, thereby inducing irradiation within the human body. 15 Nuclear reactions of N(p,α)¹²C; The six-dimensional adjustable treatment bed is set within the irradiation range of the proton beam precision irradiation device and is used to support the patient and adjust the patient's position so that the tumor lesion area is aligned with the proton beam irradiation area. A nitrogen-15-glutamine targeted drug delivery aid component for achieving precise targeted drug delivery of nitrogen-15-labeled glutamine to the tumor lesion area; The real-time nuclear reaction and dose monitoring system is electrically linked to the proton beam precision irradiation device and the nitrogen-15-glutamine targeted drug delivery auxiliary component; The real-time nuclear reaction and dose monitoring system is configured to monitor the proton beam irradiation dose and the nuclear reaction process in the body, and adjust the proton beam parameters of the proton beam precision irradiation device according to the monitoring results. The nitrogen-15-glutamine targeted drug delivery auxiliary component includes a micro-precision injection unit, a targeted positioning and fixation unit, a drug isothermal storage unit, and a drug delivery parameter control unit. The micro-precision injection unit, including a medical micro-injection pump, a sterile injection syringe, and a disposable anti-leakage injection needle, is used to achieve quantitative injection of the preparation. The targeted positioning and fixation unit includes a medical adjustable positioning frame, a lesion-fitting fixation base, and a three-dimensional micro-adjustment clamp for the needle body, which is used to position and fix the injection needle body in the tumor lesion target area, with an overall positioning accuracy of ±0.05mm. A drug constant-temperature storage unit, which is a medical-grade low-temperature constant-temperature storage structure, is used to store nitrogen-15-glutamine preparations at a constant temperature of 2~8℃; and A drug administration parameter control unit, which is electrically connected to the micro-precision injection unit, is used to set and control injection parameters.

2. The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reaction according to claim 1, characterized in that, The proton beam precision irradiation device includes a proton accelerator, an energy selection system, a beam transmission vacuum tube, a beam parameter control component, and a rotatable proton beam collimator. The proton accelerator is a cyclotron or synchrotron, used to generate a therapeutic proton beam. The energy selection system is connected to the beam extraction end of the proton accelerator; The beam transmission vacuum tube passes horizontally through the shielding wall, with one end connected to the energy selection system and the other end connected to the rotatable proton beam collimator. The beam parameter control component is electrically connected to the proton accelerator, the energy selection system, and the real-time nuclear reaction and dose monitoring system.

3. The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions according to claim 2, characterized in that, The rotatable proton beam collimator is rotatably mounted on one side of the shielding wall via a gyroscopic support; The energy selection system is configured to place the proton beam within a preset reaction energy region when it reaches the tumor lesion area; The inner ring of the gyro bearing is fixedly connected to the shielding wall, and the outer ring is fixedly connected to the rotatable proton beam collimator. The rotatable proton beam collimator can achieve stepless rotation from 0 to 360° through the gyro bearing to adjust the incident angle of the proton beam. And / or, the rotatable proton beam collimator is made of a composite material of lead and zirconium boride; it has a conical hollow channel inside, and the inner wall of the channel is provided with a boron-containing absorption layer to limit the irradiation range of the proton beam and reduce the scattered radiation at the edge of the beam.

4. The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reaction according to claim 2, characterized in that, The beam parameter control component includes an energy regulation module and a flux regulation module; The energy adjustment module is connected to the energy selection system and is used to adjust the incident energy of the proton beam; The proton beam flux density adjustment range of the flux adjustment module is 10. 8 ~10 10 ·cm -2 ·s -1 ; The flux regulation module is also used to receive feedback signals from the real-time nuclear reaction and dose monitoring system to achieve closed-loop regulation of flux density.

5. The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions according to claim 1, characterized in that, The six-dimensional adjustable treatment bed includes a bed body, a lifting assembly, a horizontal movement assembly, a rotation assembly, and a body position fixing assembly; The bed is used to carry the patient; The lifting assembly is used to adjust the position of the bed in the vertical direction; The horizontal movement component is used to adjust the position of the bed in the left-right and front-back directions; The rotating assembly is used to adjust the attitude of the bed about the X-axis, Y-axis and / or Z-axis; The positioning fixation component is used to fix the patient's position and includes one or more of the following: a malleable soft pad, a thermoplastic film, a medical fixation strap, a head, neck and shoulder fixation frame, and a trunk positioning frame.

6. The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions according to claim 1, characterized in that, The radiation shielding and safety interlocking system includes a shielding wall, a treatment room shielding layer, a local shielding component for the non-lesion area of ​​the patient, a beam transmission pipeline through-wall shielding sleeve, and a collimator connection end shielding cover. The shielding wall is used to enclose the treatment room. The shielding wall is a composite concrete wall with 5% boron powder and 3% tungsten powder added inside. The shielding layer of the treatment room is provided on the walls, floor and / or ceiling of the treatment room; The local shielding component for non-lesion areas of the patient is used to fit and be placed on the non-lesion areas of the patient's body surface; The beam transmission pipeline through-wall shielding sleeve is installed at the location where the beam transmission pipeline passes through the shielding wall; The collimator connection end shield is located in the connection area between the rotatable proton beam collimator and the shielding wall.

7. The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reaction according to claim 6, characterized in that, The entire shielding layer of the treatment room is made of boron polyethylene board with a thickness of 8-10cm, which is fully covered on the walls, floor and ceiling of the treatment room, and its shielding efficiency for scattered protons is greater than 99%. The entrance to the treatment room is equipped with a double-layer lead plate with a 5cm thick boron polyethylene shielding door sandwiched in between, and is also equipped with a radiation interlocking device for automatic locking when the proton beam is turned on. The through-wall shielding sleeve is a composite structure of double-layer boron polyethylene and lead core, used to absorb thermal neutrons and attenuate gamma rays. The shield is a composite structure with a stainless steel outer shell and a 10cm thick boron polyethylene lining, and it rotates coaxially with the rotatable proton beam collimator.

8. The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reaction according to claim 1, characterized in that, The real-time nuclear reaction and dose monitoring system includes: A gamma-ray nuclear reaction monitoring unit is used to capture the¹ 5 The characteristic γ-rays in the 4.4 MeV energy range generated during the de-excitation of ¹²C in the N(p,α)¹²C nuclear reaction were used to monitor the nuclear reaction process in situ. The data processing module is used to estimate the occurrence of nuclear reactions in the body based on the gamma-ray signal and the proton beam dose parameters; The feedback control module is electrically connected to the beam parameter control component in the proton beam precision irradiation device and is used to send control signals based on the calculation results.

9. The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reaction according to claim 8, characterized in that, The gamma-ray nuclear reaction monitoring unit includes four gamma-ray detectors arranged in a ring array around the treatment room at a distance of 100 cm from the tumor lesion target area. The gamma-ray detector is a NaI(Tl) scintillator detector with an energy response range of 0.5–10 MeV, a detection efficiency of more than 20% for gamma rays in the 4.4 MeV energy range, and a response time of ≤10 ms. Each of the gamma-ray detectors is equipped with a lead collimation sleeve and is fixed by an adjustable bracket with an installation accuracy of ±1cm. The detection efficiency, geometric response, and energy response of the gamma-ray detector are obtained through at least one of standard source calibration or Monte Carlo simulation.

10. The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reaction according to claim 8, characterized in that, The data processing module is configured as follows: The count rate of characteristic gamma rays in the 4.4 MeV energy region measured by the gamma-ray nuclear reaction monitoring unit was obtained, and the count rate was determined according to the nuclear physics formula R. 反应 =N γ / (ε·Ω·P), converting the count rate into ¹ in vivo. 5 N(p,α)¹²C nuclear reaction rate R 反应 ,in Ω represents the detector's absolute detection efficiency, P represents the detector's solid angle relative to the reaction source, and P represents the branching ratio of the characteristic γ-rays emitted in the 4.4 MeV energy range during the ¹¹²C de-excitation process.

11. The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reaction according to claim 10, characterized in that, The feedback control module is configured as follows: The nuclear reaction rate or relative intensity distribution of nuclear reactions estimated by the data processing module is compared with a preset target range. When the nuclear reaction rate or the relative intensity distribution of the nuclear reaction is lower than a preset lower limit, an enhanced irradiation signal is sent to the proton beam irradiation device. When the nuclear reaction rate or the relative intensity distribution of the nuclear reaction is higher than a preset upper limit, a suppression irradiation signal or a beam shut-off signal is sent to the proton beam irradiation device. When the nuclear reaction and dose online monitoring system detects detector abnormalities, dose rate abnormalities, beam spot position abnormalities, or treatment room interlocking abnormalities, it sends a safety shutdown command to the proton beam irradiation device.

12. The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions according to claim 1, characterized in that, In the micro-precision injection unit: The medical micro-infusion pump is a medical-grade high-precision plunger-type structure with a radiation-proof ABS shell. Its injection speed adjustment range is 0.1~10mL / h, and the dose control accuracy is ±0.01mL. The disposable anti-leakage injection needle has a micro-sized drug dispensing hole on the side wall of the needle tube, and its needle seat is equipped with an anti-leakage sealing ring.

13. The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions according to claim 1, characterized in that, In the targeted positioning and fixing unit: The medical adjustable positioning frame is used to connect the lesion-fitting fixing base and the needle body three-dimensional fine-tuning clamp; The lesion-fitting fixation base is made of medical-grade flexible silicone material with embedded shaped metal wires. The needle body three-dimensional micro-adjustment fixture can achieve micron-level micro-adjustment in X / Y / Z axes with an adjustment accuracy of ±0.1mm to adapt to injection needles of different diameters.

14. The radiotherapy system based on real-time monitoring of proton-induced nitrogen-15 nuclear reactions according to claim 1, characterized in that, The drug administration parameter control unit includes: An embedded data processor is used to store patient drug administration parameters and perform closed-loop control of injection speed and dosage. When the actual parameters deviate from the set parameters by more than ±0.1%, an alarm is triggered and automatic correction is performed. A wireless communication module is used to transmit data between the data processor and the remote control terminal; The alarm module is used to issue an alarm signal when the actual injection speed, actual injection dose, needle position, or drug storage temperature exceeds a preset threshold, and to pause the injection or prompt the operator to make corrections.

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