A fully automatic radiopharmaceutical synthesizer optimization calibration method and system

Abstract

The present invention relates to the technical field of chemical or physical related equipment, and specifically to a method and system for optimizing and calibrating a fully automatic radiopharmaceutical synthesizer. The present invention first obtains monitoring data during the synthesis of radiopharmaceuticals, and the monitoring data includes all voltage data and all radiation energy spectra of the radiopharmaceutical synthesizer in a preset historical period at each time to be optimized and calibrated; further obtains performance instability parameters, radiation hazard parameters and adverse reaction parameters of the drug synthesizer; thereby comprehensively obtaining the optimized calibration parameters of the drug synthesizer at each time to be optimized and calibrated; and adjusting the radiopharmaceutical synthesis process according to the optimized calibration parameters. Based on the performance stability of the drug synthesizer, the present invention analyzes the reaction conditions such as radiation hazards and reaction products during the drug synthesis process, optimizes and calibrates the drug synthesizer according to the actual drug reaction process, and improves the optimization and calibration effect of the drug synthesizer.

Description

Technical Field

[0001] The invention relates to the technical field of chemical or physical related equipment, and in particular to a method and system for optimizing and calibrating a fully automatic radiopharmaceutical synthesizer. Background Art

[0002] Radiopharmaceuticals play an important role in the medical field and can be used to diagnose and treat a variety of diseases; fully automatic radiopharmaceutical synthesizers are key medical equipment used to produce radiopharmaceuticals in clinical and research fields. The synthesis of radiopharmaceuticals requires highly precise control to ensure that the synthesis process of radiopharmaceuticals can be carried out safely and accurately, and meet the quality standards and safety requirements of clinical research, which is crucial for the optimization and calibration of drug synthesizers.

[0003] The existing technology mainly utilizes the built-in control system of the fully automatic radiopharmaceutical synthesizer to monitor and feedback in real time to optimize the synthesis process. However, since the automatic optimization adjustment of the fully automatic radiopharmaceutical synthesizer is usually calibrated and optimized based on the system setting parameters, it cannot be adjusted according to the actual drug reaction process, resulting in poor optimization and calibration effects. Summary of the invention

[0004] In order to solve the technical problem that the optimization and calibration effect of radiopharmaceutical synthesizers in the prior art is not good, the purpose of the present invention is to provide a fully automatic radiopharmaceutical synthesizer optimization and calibration method and system, and the technical scheme adopted is as follows:

[0005] The present invention provides a fully automatic radiopharmaceutical synthesizer optimization calibration method, the method comprising:

[0006] Acquiring monitoring data during the synthesis of radiopharmaceuticals, wherein the monitoring data includes all voltage data and all radiation energy spectra of the radiopharmaceutical synthesizer within a preset historical period at each time to be optimized and calibrated;

[0007] According to the fluctuation of the voltage data, the performance instability parameter of the drug synthesizer at each calibration moment to be optimized is obtained; according to the peak level and peak change of the characteristic peaks in all the radiation energy spectra, the radiation hazard parameter of the drug synthesizer at each calibration moment to be optimized is obtained; the preset standard energy spectrum of each radiation energy spectrum is obtained, and the adverse reaction parameter of the drug synthesizer at each calibration moment to be optimized is obtained according to the characteristic peak difference between each radiation energy spectrum and the corresponding preset standard energy spectrum;

[0008] According to the radiation hazard parameters and the adverse reaction parameters, combined with the performance instability parameters, the optimized calibration parameters of the drug synthesizer at each calibration moment to be optimized are obtained; at each calibration moment to be optimized, the radioactive drug synthesis process is adjusted according to the optimized calibration parameters.

[0009] Furthermore, the method for obtaining the radiation hazard parameters includes:

[0010] According to the peak value difference of all the characteristic peaks in each of the radiation energy spectra, the instability of the reaction conditions of the drug synthesizer at the corresponding moment of each of the radiation energy spectra is obtained, and the peak value difference is positively correlated with the instability of the reaction conditions;

[0011] According to the intensity difference between the peak values ​​of all the characteristic peaks in each radiation energy spectrum and the preset standard radiation, the radiation risk parameter of the drug synthesizer at the corresponding moment of each radiation energy spectrum is obtained, and the intensity difference is negatively correlated with the radiation risk parameter;

[0012] According to the reaction condition instability and the radiation risk parameter, the radiation hazard sub-parameter of the drug synthesizer at each moment corresponding to the radiation energy spectrum is obtained, and the reaction condition instability and the radiation risk parameter are positively correlated with the radiation hazard sub-parameter; the radiation hazard sub-parameters of the drug synthesizer at all moments corresponding to the radiation energy spectra are combined to obtain the radiation hazard parameters of the drug synthesizer at each moment to be optimized and calibrated.

[0013] Furthermore, the method for obtaining the instability of the reaction conditions includes:

[0014] In each of the radiation energy spectra, the absolute values ​​of the peak differences between all two different characteristic peaks are averaged to obtain the instability of the reaction conditions.

[0015] Furthermore, the method for obtaining the radiation risk parameter includes:

[0016] In each of the radiation energy spectra, the intensity difference between the preset standard radiation and the peak value of each of the characteristic peaks is obtained respectively, each intensity difference is normalized to obtain all normalized values; the mean of all normalized values ​​is negatively correlated and mapped, and the negative correlation mapping result is used as a radiation risk parameter.

[0017] Furthermore, the method for obtaining the adverse reaction parameter includes:

[0018] Each of the radiation energy spectra is compared with the corresponding preset standard energy spectrum to obtain additional peaks in each of the radiation energy spectra; the additional peaks are characteristic peaks in the radiation energy spectrum that do not exist in the corresponding preset standard energy spectrum, and the number of the additional peaks in all the radiation energy spectra is combined to obtain the adverse reaction parameter.

[0019] Furthermore, the method for obtaining the optimized calibration parameters includes:

[0020] Initial optimized calibration parameters are obtained according to the radiation hazard parameters and the adverse reaction parameters, and both the radiation hazard parameters and the adverse reaction parameters are positively correlated with the initial optimized calibration parameters; the results of negative correlation mapping of the performance instability parameters are used as confidence weights of the initial optimized calibration parameters, the initial optimized calibration parameters are weighted using the confidence weights, and the normalized results of the weighted results are used as the optimized calibration parameters.

[0021] Furthermore, the method for obtaining the initial optimization calibration parameters includes:

[0022] The square sum of the radiation hazard parameter and the adverse reaction parameter is subjected to a second root operation to obtain an initial optimization calibration parameter.

[0023] Furthermore, the method for adjusting the radiopharmaceutical synthesis process according to the optimized calibration parameters at each calibration moment to be optimized includes:

[0024] The adjustment process at least includes the adjustment of the reaction environment temperature;

[0025] The adjustment process of the reaction environment temperature includes: obtaining the average environment temperature in a preset historical period, taking the product of the average environment temperature and the optimized calibration parameter as the temperature reduction amplitude, subtracting the temperature reduction amplitude from the average environment temperature to obtain the optimized calibration temperature, and adjusting the temperature at the time of optimized calibration to the optimized calibration temperature.

[0026] Furthermore, the method for obtaining the preset historical period includes:

[0027] The time period between each calibration moment to be optimized and the previous adjacent calibration moment to be optimized is taken as a preset historical period; the preset historical period includes the calibration moment to be optimized but does not include the previous adjacent calibration moment to be optimized.

[0028] The present invention also proposes a fully automatic radiopharmaceutical synthesizer optimization and calibration system, which includes a memory, a processor, and a computer program stored in the memory and executable on the processor. When the processor executes the computer program, the steps of the fully automatic radiopharmaceutical synthesizer optimization and calibration method are implemented.

[0029] The present invention has the following beneficial effects:

[0030] The embodiment of the present invention first obtains monitoring data during the synthesis of radiopharmaceuticals, and the monitoring data includes all voltage data and all radiation energy spectra of the radiopharmaceutical synthesizer in the preset historical period at each time to be optimized and calibrated; according to the fluctuation of the voltage data, the performance instability parameter of the drug synthesizer is obtained; further, according to the peak level and peak change of the characteristic peaks in all radiation energy spectra, the radiation hazard parameter of the drug synthesizer is obtained; further, the preset standard energy spectrum of each radiation energy spectrum is obtained, and the adverse reaction parameter of the drug synthesizer is obtained according to the characteristic peak difference between each radiation energy spectrum and the corresponding preset standard energy spectrum; according to the radiation hazard parameter and the adverse reaction parameter, combined with the performance instability parameter, the optimized calibration parameter of the drug synthesizer at each time to be optimized and calibrated is obtained; finally, at each time to be optimized and calibrated, the radiopharmaceutical synthesis process is adjusted according to the optimized calibration parameter. On the basis of the performance stability of the drug synthesizer, the present invention analyzes the reaction conditions such as radiation hazards and reaction products in the drug synthesis process, optimizes and calibrates the drug synthesizer according to the actual drug reaction process, and improves the optimization and calibration effect of the drug synthesizer. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the technical solutions and advantages in the embodiments of the present invention or the prior art, the drawings required for use in the embodiments or the prior art descriptions are briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0032] Figure 1 A flow chart of a method for optimizing and calibrating a fully automatic radiopharmaceutical synthesizer provided by one embodiment of the present invention;

[0033] Figure 2 A flowchart of a method for obtaining radiation hazard parameters provided by an embodiment of the present invention;

[0034] Figure 3 A schematic diagram of the structure of a fully automatic radiopharmaceutical synthesizer optimization and calibration system provided by one embodiment of the present invention. DETAILED DESCRIPTION

[0035] In order to further explain the technical means and effects adopted by the present invention to achieve the predetermined invention purpose, the following is a detailed description of the method and system for optimizing and calibrating a fully automatic radiopharmaceutical synthesizer according to the present invention, its specific implementation, structure, features and effects, in conjunction with the accompanying drawings and preferred embodiments. In the following description, different "one embodiment" or "another embodiment" does not necessarily refer to the same embodiment. In addition, specific features, structures or characteristics in one or more embodiments may be combined in any suitable form.

[0036] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0037] The specific scheme of a fully automatic radiopharmaceutical synthesizer optimization calibration method and system provided by the present invention is described in detail below with reference to the accompanying drawings.

[0038] See also Figure 1 , which shows a flow chart of a method for optimizing and calibrating a fully automatic radiopharmaceutical synthesizer provided by an embodiment of the present invention, specifically comprising:

[0039] Step S1, acquiring monitoring data during the radiopharmaceutical synthesis process, the monitoring data including all voltage data and all radiation energy spectra of the radiopharmaceutical synthesizer within a preset historical period at each time to be optimized and calibrated.

[0040] In one embodiment of the present invention, monitoring data during the synthesis of radioactive drugs is first obtained, and the monitoring data includes relevant data of the radioactive drug synthesizer in a preset historical time period at each calibration moment to be optimized; wherein the optimization calibration frequency is once every five minutes, that is, the drug synthesis start time is taken as the starting point, and every five minutes is a calibration moment to be optimized. For example, the synthesis experiment starts at 10 a.m., the first calibration moment to be optimized is 10:05, the second acquisition moment to be optimized is 10:10, and so on, until the end of the experiment; then the time period between each calibration moment to be optimized and the adjacent previous calibration moment to be optimized is taken as a preset historical time period, wherein the preset historical time period includes the calibration moment to be optimized, but does not include the adjacent previous calibration moment to be optimized, for example, 10:00-10:05 is the preset historical time period for the first calibration moment to be optimized, which is not repeated here.

[0041] At the same time, within the preset historical time period, monitoring data is collected at a preset sampling frequency, and the monitoring data includes all voltage data and all radiation energy spectra of the radiopharmaceutical synthesizer within the preset historical time period at each time to be optimized and calibrated, and the preset sampling frequency is once every 30 seconds; at each sampling moment in the preset historical time period, a digital voltmeter is used to monitor the voltage data of the power supply voltage of the radiopharmaceutical synthesizer during operation, and the corresponding radiation measuring equipment is used to measure the radiation energy spectrum that may occur during the synthesis of radiopharmaceuticals, specifically including α-ray energy spectrum diagram, β-ray energy spectrum diagram, γ-ray energy spectrum diagram, etc.

[0042] It should be noted that collecting radiation energy spectrum is an existing technology well known to those skilled in the art and will not be described in detail here; in other embodiments of the present invention, the implementer may also set the optimized calibration frequency and the preset sampling frequency by himself.

[0043] It should be noted that the analysis and optimization calibration process of the drug synthesizer at each calibration moment to be optimized is consistent, and only any one of the calibration moments to be optimized is used for description herein.

[0044] Step S2, according to the fluctuation of voltage data, obtain the performance instability parameters of the drug synthesizer at each calibration moment to be optimized; according to the peak level and peak change of the characteristic peaks in all radiation energy spectra, obtain the radiation hazard parameters of the drug synthesizer at each calibration moment to be optimized; obtain the preset standard energy spectrum of each radiation energy spectrum, and obtain the adverse reaction parameters of the drug synthesizer at each calibration moment to be optimized based on the characteristic peak difference between each radiation energy spectrum and the corresponding preset standard energy spectrum.

[0045] Considering that the voltage supply stability affects the output performance stability of the drug synthesizer to a certain extent, the performance instability parameters of the drug synthesizer are first obtained according to the fluctuation of the voltage data; the more severe the voltage fluctuation, the lower the operating performance of the drug synthesizer, the lower the effectiveness of the analysis of the real-time radiation monitoring data, and the lower the accuracy of the evaluation of the drug reaction process, so the stability parameters are first obtained to prepare for the follow-up.

[0046] Preferably, in one embodiment of the present invention, considering that the greater the amplitude change of voltage data at adjacent acquisition moments, the more violent its fluctuation is; the method for obtaining performance instability parameters includes:

[0047] In a preset historical period, the performance instability parameters of the drug synthesizer are obtained according to the amplitude changes of the voltage data at all adjacent acquisition moments.

[0048] As an example, the performance instability parameter is calculated as: ;in, is the performance instability parameter of the drug synthesizer at each calibration moment to be optimized; is the index of voltage data; The total amount of voltage data in a preset historical period at each time to be optimized and calibrated; For the Voltage data; For the Voltage data; is the absolute value symbol.

[0049] In other embodiments, the implementer may also directly calculate the variance or standard deviation of the voltage data as the fluctuation of the voltage data, which will not be described in detail.

[0050] Considering that radioactive isotopes are usually used in the drug synthesis process, they will release high-energy particles or photons during nuclear decay, which has certain radiation hazards to the human body. At the same time, the radiation energy may also directly cause changes in the possible reaction conditions of the drug, such as increasing the temperature of the reaction environment and causing changes in the physical or chemical properties of the reaction substances. Therefore, in the automatic optimization and calibration process of the drug synthesizer, it is very important to optimize and reduce the radiation impact; considering that the radiation energy spectrum can reflect the energy distribution of the released particles, and then the radiation intensity can be evaluated; and because the characteristic peaks in the radiation energy spectrum have similar or the same heights, it reflects that the generation rate of radioactive isotopes or the nuclear decay process in the synthesis process is relatively stable, which indirectly illustrates the relative stability of the reaction conditions; when the reaction conditions are more unstable and the peak level of the characteristic peak is higher, it means that the greater the confidence of the radiation intensity is, the greater the radiation hazard is; therefore, the embodiment of the present invention obtains the radiation hazard parameters of the drug synthesizer according to the peak level and peak change of the characteristic peaks in all radiation energy spectra.

[0051] Preferably, in one embodiment of the present invention, the method for obtaining radiation hazard parameters includes:

[0052] See also Figure 2 , which shows a flow chart of a method for obtaining radiation hazard parameters provided by an embodiment of the present invention, specifically comprising:

[0053] Step S201, obtaining the reaction condition instability of the drug synthesizer at the corresponding moment of each radiation energy spectrum according to the peak value difference of all characteristic peaks in each radiation energy spectrum, and the peak value difference is positively correlated with the reaction condition instability.

[0054] In a preferred embodiment of the present invention, the method for obtaining the instability of reaction conditions comprises:

[0055] In each radiation energy spectrum, the absolute values ​​of the peak differences between all two different characteristic peaks are averaged to obtain the instability of the reaction conditions.

[0056] As an example, firstly, all peak points in each radiation energy spectrum are obtained by using a peak detection algorithm, and the nearest minimum points on both sides of the peak points are searched as valley points to obtain a characteristic peak. The acquisition of characteristic peaks is a well-known technology and will not be described in detail here. The calculation formula of the instability of the reaction conditions is: ;in, In the preset historical period for each time to be optimized and calibrated, The reaction conditions of the drug synthesizer at the time corresponding to each radiation energy spectrum are unstable; In the preset historical period for each time to be optimized and calibrated, The index of the pairwise combination of characteristic peaks in the radiation energy spectrum; is the total number of pairwise combinations between characteristic peaks; In the preset historical period for each time to be optimized and calibrated, The radiation energy spectrum The peak value of a characteristic peak, that is, the radiation intensity; In the preset historical period for each time to be optimized and calibrated, The radiation energy spectrum The peak value of the characteristic peak, that is, the radiation intensity; The characteristic peak and The characteristic peaks are not the same characteristic peak; is the absolute value symbol.

[0057] In other embodiments, the implementer may also use discrete measurement means such as variance or standard deviation to evaluate the peak similarity of characteristic peaks. The larger the variance, the greater the difference in the corresponding amplitudes of the characteristic peaks, which will not be elaborated.

[0058] Step S202, according to the intensity difference of the peak values ​​of all characteristic peaks in each radiation energy spectrum relative to the preset standard radiation, the radiation risk parameter of the drug synthesizer at the corresponding moment of each radiation energy spectrum is obtained, and the intensity difference is negatively correlated with the radiation risk parameter.

[0059] In a preferred embodiment of the present invention, the method for obtaining radiation risk parameters includes:

[0060] In each radiation energy spectrum, the intensity difference between the preset standard radiation and the peak value of each characteristic peak is obtained respectively, each intensity difference is normalized to obtain all normalized values; the means of all normalized values ​​are negatively correlated and mapped, and the negative correlation mapping result is used as the radiation risk parameter.

[0061] As an example, the radiation risk parameter is calculated as: ;in, In the preset historical period for each time to be optimized and calibrated, The radiation risk parameters of the drug synthesizer at the moment when each radiation energy spectrum corresponds to; is the index of the characteristic peak; is the total number of characteristic peaks; is an S-type function; It is the preset standard radiation; In the preset historical period for each time to be optimized and calibrated, The radiation energy spectrum The peak value of the characteristic peak; is a non-zero positive parameter, and is taken as 1 in this formula to prevent the denominator from being meaningless.

[0062] In the above formula, when the peak value of the characteristic peak is greater than the preset standard radiation and the greater the difference, the difference is negative, indicating that the radiation intensity of the characteristic peak has far exceeded the standard radiation intensity specified in the experiment, which may have a certain impact on the human body or the synthesis result; the smaller the value is after mapping it to the S-type function, and the larger the corresponding radiation risk parameter is after further adding a non-zero positive parameter and performing a reciprocal operation; in other examples, the implementer can also use the denominator in the above formula as an exponential function with the natural constant e as the base In , to perform negative correlation mapping, other negative correlation mapping methods can also be used, which will not be described here.

[0063] It should be noted that the preset standard radiation is the upper limit of radiation that the human body can withstand or the radiation intensity that does not affect the synthesis result. It needs to be confirmed based on the laboratory's safety protection level, the properties of the drug and relevant experimental regulations. The standard radiation in different situations may be different, which will not be elaborated here.

[0064] Step S203, according to the reaction condition instability and the radiation risk parameters, the radiation hazard sub-parameters of the drug synthesizer at the corresponding moment of each radiation energy spectrum are obtained, and the reaction condition instability and the radiation risk parameters are positively correlated with the radiation hazard sub-parameters; the radiation hazard sub-parameters of the drug synthesizer at the corresponding moment of all radiation energy spectra are combined to obtain the radiation hazard parameters of the drug synthesizer.

[0065] Since high radiation energy usually affects the stability of reaction conditions and endangers human health, as an example, the reaction condition instability and radiation risk parameters are multiplied and combined to obtain a radiation hazard sub-parameter, and the radiation hazard sub-parameters of the drug synthesizer at the corresponding moment of all radiation energy spectra are further averaged to obtain the radiation hazard parameter.

[0066] Considering that during the radiopharmaceutical synthesis reaction, the instability of the reaction conditions usually results in the appearance of incompletely purified compounds, decay products of nuclides or reaction by-products in the final reaction products, which usually appear as additional unexpected characteristic peaks in the radiation energy spectrum. These unexpected products usually affect the purity and quality of the drug. Therefore, it is very important to optimize and calibrate the drug synthesizer according to the analysis and evaluation of the actual reaction conditions to improve the quality of the drug. The embodiment of the present invention will first obtain a preset standard energy spectrum for each radiation energy spectrum, and further obtain the adverse reaction parameters of the drug synthesizer based on the characteristic peak differences between each radiation energy spectrum and the corresponding preset standard energy spectrum. The more the characteristic peak differences, the greater the possibility of an adverse reaction process, and the greater the necessity for subsequent adjustments.

[0067] Preferably, in one embodiment of the present invention, the method for obtaining adverse reaction parameters includes:

[0068] Each radiation energy spectrum is compared with the corresponding preset standard energy spectrum to obtain additional peaks in each radiation energy spectrum; the additional peaks are characteristic peaks in the radiation energy spectrum that do not exist in the corresponding preset standard energy spectrum; the number of additional peaks in all radiation energy spectra is combined to obtain the adverse reaction parameters.

[0069] As an example, characteristic peaks corresponding to the same horizontal coordinates in the radiation energy spectrum are regarded as the same peaks. If a characteristic peak that does not exist in the preset standard energy spectrum appears in the radiation energy spectrum, the peak is regarded as an additional peak. The number of additional peaks in all radiation energy spectra in the preset historical period is averaged to obtain the adverse reaction parameter.

[0070] In other examples, the implementer may also set a deviation range, that is, when the horizontal axis deviation is less than 5%, it can also be identified as the same peak.

[0071] It should be noted that the preset standard energy spectrum is the ideal radiation energy spectrum at each sampling moment obtained under a standard test environment, which can be obtained by implementers based on existing literature or known experimental data records and will not be elaborated here.

[0072] Step S3, according to the radiation hazard parameters and adverse reaction parameters, combined with the performance instability parameters, obtain the optimized calibration parameters of the drug synthesizer at each time to be optimized and calibrated; adjust the radioactive drug synthesis process according to the optimized calibration parameters.

[0073] Taking into account the radiation hazard parameters combined with the safety of the drug synthesis process and the impact on the reaction environment, the real-time synthesis effect of the drug synthesizer was preliminarily evaluated; and the adverse reaction parameters were based on the real-time product situation in the reaction process to further evaluate the reaction effect of the drug synthesizer; and considering that the power supply voltage of the drug synthesizer is stable, it is crucial to the effectiveness of the analysis of real-time radiation monitoring data. The smaller the performance instability parameter, the more accurate the analysis and evaluation of the synthesis effect of the drug synthesizer affected by non-external factors; therefore, the embodiment of the present invention obtains the optimized calibration parameters of the drug synthesizer at each time to be optimized and calibrated according to the radiation hazard parameters and the adverse reaction parameters, combined with the performance instability parameters. The optimized calibration parameters evaluate the operating effect of the real-time drug synthesizer by analyzing the reaction situation in real time while considering the influence of non-external conditions, so that the actual drug reaction process can be accurately adjusted in the hope of obtaining good drug synthesis results.

[0074] Preferably, in one embodiment of the present invention, the method for obtaining the optimized calibration parameters includes:

[0075] The initial optimization calibration parameters are obtained according to the radiation hazard parameters and the adverse reaction parameters. Both the radiation hazard parameters and the adverse reaction parameters are positively correlated with the initial optimization calibration parameters. The results of the negative correlation mapping of the performance instability parameters are used as the confidence weights of the initial optimization calibration parameters. The initial optimization calibration parameters are weighted using the confidence weights, and the normalized results of the weighted results are used as the optimization calibration parameters. Among them, the square sum of the radiation hazard parameters and the adverse reaction parameters is quadratically rooted to obtain the initial optimization calibration parameters.

[0076] As an example, the calculation formula for optimizing the calibration parameters is: ;in, Optimizing calibration parameters for the drug synthesizer at each calibration moment to be optimized; is the hyperbolic tangent function, used for normalization; is the performance instability parameter of the drug synthesizer at each calibration moment to be optimized; is an exponential function with the natural constant e as base; is the confidence weight at each calibration moment to be optimized; The radiation hazard parameters of the drug synthesizer at each calibration moment to be optimized; The adverse reaction parameters of the drug synthesizer at each calibration moment to be optimized; Initial optimized calibration parameters for the drug synthesizer at each calibration moment to be optimized.

[0077] In the above formula, the radiation hazard parameter and the adverse reaction parameter are specifically merged in the form of Euclidean norm to obtain the initial optimization calibration parameter, and then the performance instability parameter is negatively correlated and mapped as the confidence weight and multiplied and merged with the initial optimization calibration parameter, and further normalized to obtain the optimization calibration parameter, wherein the negative correlation mapping of the performance instability parameter reflects the confidence of the radiation hazard parameter and the adverse reaction parameter, that is, the accuracy of the reaction process related data collected when the performance of the drug synthesizer is stable. When the performance instability parameter is larger, the operating performance of the drug synthesizer is unstable, and the obtained radiation energy spectrum may not reflect the normal synthesis process. Then, the accuracy of the radiation monitoring and adverse reaction during the synthesis of the synthetic drug is low, and the confidence of the obtained initial optimization calibration parameter is also low; on the contrary, when the performance instability parameter is smaller, the operating performance of the drug synthesizer is stable, the confidence of the obtained initial optimization calibration parameter is also higher, and the accuracy of the subsequent optimization calibration is also higher; the initial optimization calibration parameter reflects the reaction effect of the drug synthesizer. The larger the initial optimization calibration parameter, the more serious the radiation hazard and adverse reaction, the worse the reaction effect, and the greater the necessity and adjustment degree of the corresponding optimization calibration. Once the optimized calibration parameters are obtained, the radiopharmaceutical synthesis process can be adjusted according to the optimized calibration parameters.

[0078] Preferably, in one embodiment of the present invention, considering that temperature is a crucial factor in the drug synthesis reaction, as the synthesis experiment proceeds, high-energy particles may be released during nuclear decay, which may cause the reaction temperature to rise, thereby affecting the reaction effect. Therefore, the adjustment process at least includes the adjustment of the reaction environment temperature; specifically, it includes: obtaining the average ambient temperature within a preset historical period, taking the product of the average ambient temperature and the optimized calibration parameter as the cooling amplitude, subtracting the cooling amplitude from the average ambient temperature to obtain the optimized calibration temperature, and adjusting the temperature at the time of optimization and calibration to be adjusted to the optimized calibration temperature; by optimizing the calibration parameters, the influence of the temperature increase is appropriately reduced, thereby ensuring that subsequent reactions can proceed smoothly to obtain ideal drug synthesis results.

[0079] In other embodiments of the present invention, considering that in some drug synthesis experiments, experimental related materials are usually fed according to preset feeding amounts and feeding times by a preset automatic control program, the adjustment process of the drug synthesizer may also include the adjustment of isotope dosage; considering that high-energy particles, i.e., excessive radiation, are released during nuclear decay, it is not only harmful to the human body, but may also cause changes in the properties of some chemical substances in the drug synthesis experiment; therefore, when the optimization calibration parameter is larger, it is considered to appropriately reduce the dosage of radioactive isotopes in the hope of obtaining the best synthesis effect; specifically, all preset feeding amounts at the current time to be optimized and calibrated and the next time to be optimized and calibrated can be obtained, and the optimization calibration parameter can be multiplied by the preset feeding amount to obtain the feeding reduction amount, and then the adjusted feeding amount is obtained, so as to appropriately reduce the radiation intensity while ensuring the synthesis effect.

[0080] In summary, the embodiment of the present invention first obtains monitoring data during the synthesis of radiopharmaceuticals, and the monitoring data includes all voltage data and all radiation energy spectra of the radiopharmaceutical synthesizer in a preset historical period at each time to be optimized and calibrated; further obtains the performance instability parameters, radiation hazard parameters and adverse reaction parameters of the drug synthesizer; thereby comprehensively obtaining the optimized calibration parameters of the drug synthesizer at each time to be optimized and calibrated; and adjusts the radiopharmaceutical synthesis process according to the optimized calibration parameters. Based on the performance stability of the drug synthesizer, the present invention analyzes the reaction conditions such as radiation hazards and reaction products during the drug synthesis process, optimizes and calibrates the drug synthesizer according to the actual drug reaction process, and improves the optimization and calibration effect of the drug synthesizer.

[0081] Based on the same inventive concept, one embodiment of the present invention also provides a fully automatic radiopharmaceutical synthesizer optimization calibration system, see Figure 3The system includes a memory 301, a processor 302 and a computer program 303, wherein the memory is used to store the corresponding computer program, the processor is used to run the corresponding computer program, and when the computer program runs in the processor, it can implement a fully automatic radiopharmaceutical synthesizer optimization calibration method described in steps S1-S3.

[0082] It should be noted that the sequence of the above embodiments of the present invention is only for description and does not represent the advantages and disadvantages of the embodiments. The processes depicted in the accompanying drawings do not necessarily require the specific order or continuous order shown to achieve the desired results. In some embodiments, multitasking and parallel processing are also possible or may be advantageous.

[0083] The various embodiments in this specification are described in a progressive manner, and the same or similar parts between the various embodiments can be referenced to each other, and each embodiment focuses on the differences from other embodiments.

Claims

1. A method for optimizing and calibrating a fully automatic radiopharmaceutical synthesizer, characterized in that: The method comprises: Acquiring monitoring data during the synthesis of radiopharmaceuticals, wherein the monitoring data includes all voltage data and all radiation energy spectra of the radiopharmaceutical synthesizer within a preset historical period at each time to be optimized and calibrated; According to the fluctuation of the voltage data, the performance instability parameter of the drug synthesizer at each calibration moment to be optimized is obtained; according to the peak level and peak change of the characteristic peaks in all the radiation energy spectra, the radiation hazard parameter of the drug synthesizer at each calibration moment to be optimized is obtained; the preset standard energy spectrum of each radiation energy spectrum is obtained, and the adverse reaction parameter of the drug synthesizer at each calibration moment to be optimized is obtained according to the characteristic peak difference between each radiation energy spectrum and the corresponding preset standard energy spectrum; According to the radiation hazard parameter and the adverse reaction parameter, combined with the performance instability parameter, the optimized calibration parameter of the drug synthesizer at each time to be optimized and calibrated is obtained; at each time to be optimized and calibrated, the radioactive drug synthesis process is adjusted according to the optimized calibration parameter; The method for obtaining the preset historical period includes: The time period between each calibration moment to be optimized and the previous calibration moment to be optimized is used as a preset historical period; the preset historical period includes the calibration moment to be optimized but does not include the previous calibration moment to be optimized; The calculation formula of the performance instability parameter is: ;in, is the performance instability parameter of the drug synthesizer at each calibration moment to be optimized; is the index of voltage data; The total amount of voltage data in a preset historical period at each time to be optimized and calibrated; For the Voltage data; For the Voltage data; is the absolute value symbol; The method for obtaining the radiation hazard parameters includes: According to the peak value difference of all the characteristic peaks in each of the radiation energy spectra, the instability of the reaction conditions of the drug synthesizer at the corresponding moment of each of the radiation energy spectra is obtained, and the peak value difference is positively correlated with the instability of the reaction conditions; According to the intensity difference between the peak values ​​of all the characteristic peaks in each radiation energy spectrum and the preset standard radiation, the radiation risk parameter of the drug synthesizer at the corresponding moment of each radiation energy spectrum is obtained, and the intensity difference is negatively correlated with the radiation risk parameter; According to the reaction condition instability and the radiation risk parameter, the radiation hazard sub-parameter of the drug synthesizer at each moment corresponding to the radiation energy spectrum is obtained, and the reaction condition instability and the radiation risk parameter are both positively correlated with the radiation hazard sub-parameter; the radiation hazard sub-parameters of the drug synthesizer at all moments corresponding to the radiation energy spectra are combined to obtain the radiation hazard parameter of the drug synthesizer at each moment to be optimized and calibrated; The method for obtaining the adverse reaction parameter comprises: Compare each of the radiation energy spectra with the corresponding preset standard energy spectra to obtain additional peaks in each of the radiation energy spectra; the additional peaks are characteristic peaks in the radiation energy spectra that do not exist in the corresponding preset standard energy spectra, and the number of the additional peaks in all the radiation energy spectra is combined to obtain adverse reaction parameters; The method for obtaining the optimized calibration parameters includes: Acquire initial optimization calibration parameters according to the radiation hazard parameters and the adverse reaction parameters, wherein the radiation hazard parameters and the adverse reaction parameters are both positively correlated with the initial optimization calibration parameters; use the result of negative correlation mapping of the performance instability parameters as the confidence weight of the initial optimization calibration parameters, weight the initial optimization calibration parameters using the confidence weight, and use the normalized result of the weighted result as the optimization calibration parameters; The method for adjusting the radiopharmaceutical synthesis process according to the optimized calibration parameters at each calibration moment to be optimized comprises: The adjustment process at least includes the adjustment of the reaction environment temperature; The adjustment process of the reaction environment temperature includes: obtaining the average environment temperature in a preset historical period, taking the product of the average environment temperature and the optimized calibration parameter as the temperature reduction amplitude, subtracting the temperature reduction amplitude from the average environment temperature to obtain the optimized calibration temperature, and adjusting the temperature at the time of optimized calibration to the optimized calibration temperature.

2. A method for optimizing and calibrating a fully automatic radiopharmaceutical synthesizer according to claim 1, characterized in that: The method for obtaining the instability of the reaction conditions comprises: In each of the radiation energy spectra, the absolute values ​​of the peak differences between all two different characteristic peaks are averaged to obtain the instability of the reaction conditions.

3. The method for optimizing and calibrating a fully automatic radiopharmaceutical synthesizer according to claim 1, characterized in that: The method for obtaining the radiation risk parameter includes: In each of the radiation energy spectra, the intensity difference between the preset standard radiation and the peak value of each of the characteristic peaks is obtained respectively, each intensity difference is normalized to obtain all normalized values; the mean of all normalized values ​​is negatively correlated and mapped, and the negative correlation mapping result is used as a radiation risk parameter.

4. A method for optimizing and calibrating a fully automatic radiopharmaceutical synthesizer according to claim 1, characterized in that: The method for obtaining the initial optimization calibration parameters includes: The square sum of the radiation hazard parameter and the adverse reaction parameter is subjected to a second root operation to obtain an initial optimization calibration parameter.

5. A fully automatic radiopharmaceutical synthesizer optimization calibration system, characterized in that: The system includes a memory, a processor, and a computer program stored in the memory and executable on the processor. When the processor executes the computer program, the steps of a method for optimizing and calibrating a fully automatic radiopharmaceutical synthesizer as described in any one of claims 1 to 4 are implemented.

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