Radiopharmaceutical activity measurement device and method based on passive efficiency calibration

Abstract

The present invention discloses a radiopharmaceutical activity measurement device and method based on passive efficiency scale, comprising a detector base, a CZTγ spectrum detector, a sample tray, a sample holder, and a stopper, wherein the CZTγ spectrum detector is placed on the detector base; the sample holder is fixed above the detector base; the sample tray is horizontally arranged in the sample holder; the sample tray is used to place a radioactive solution container, and the radioactive solution is placed in the radioactive solution container. The present invention uses a new semiconductor CZTγ spectrum detector to record the γ rays emitted by the radiopharmaceutical, and identifies different nuclides through the γ-ray spectrum. The present invention can measure the activity of radiopharmaceutical samples under any conditions, and is not limited by the geometric shape and material of the radiopharmaceutical container, the volume of the radiopharmaceutical, the distance and relative position between the sample and the detector, and can meet the needs of multiple scenarios in the diagnosis and treatment of radiopharmaceuticals.

Description

Technical Field

[0001] The present invention relates to the technical field of radioactive drug activity measurement, and in particular to a radioactive drug activity measurement device and method based on passive efficiency calibration. Background Art

[0002] The activity of a radiopharmaceutical refers to the number of radionuclide nuclei that decay per unit time. In nuclear medicine, the dosage of radiopharmaceuticals is measured in activity, and the activity of radiopharmaceuticals administered to patients directly affects the treatment or diagnosis effect. my country's pharmacopoeia requires that the activity of radiopharmaceuticals be measured before clinical use, and the deviation of the activity cannot exceed ±10%. At the same time, there are clear regulations on the impurity content in radiopharmaceuticals. The European Pharmacopoeia and the United States Pharmacopoeia also have the same requirements. Therefore, the activity measurement of radiopharmaceuticals is very important in nuclear medicine.

[0003] At present, activity meters are commonly used in nuclear medicine to measure the activity of radioactive drugs. Activity meters measure activity by detecting the microcurrent generated by the cumulative effect of radiation, and cannot measure the energy spectrum of gamma rays emitted by nuclides. Activity meters have problems such as difficulty in equipment calibration, low reliability of results, inability to measure low-activity samples, limited measurement conditions, inability to identify nuclides, and difficulty in measuring new radioactive nuclides.

[0004] In order to solve the above problems, a method for measuring the activity of radiopharmaceuticals based on γ spectrum is needed. The current γ spectrum measurement equipment includes HPGe, CZT, NaI, LaBr3, CeBr3 and other detectors, but NaI, LaBr3, CeBr3 have poor energy resolution, HPGe needs to work at liquid nitrogen temperature, and is expensive, which is not suitable for clinical application of radiopharmaceuticals. CZT detector has good energy resolution, can work at room temperature, is lightweight, and has moderate detection efficiency, so it can be used for measuring the activity of radiopharmaceuticals.

[0005] Cadmium zinc telluride (CZT) detector is a new type of semiconductor gamma spectrum detector. It has been widely used in medicine, astrophysics, homeland security, environmental protection and other fields. CZT detector is mainly used to measure the energy spectrum of X-rays or gamma rays.

[0006] The activity analysis method of measuring the gamma-ray energy spectrum of radioactive drugs using CZT detectors can not only obtain the activity of the nuclide to be measured, but also identify the type of nuclide and quantitatively analyze the impurities or contaminating nuclides in the radioactive drugs. It can be used as a quality control measurement device for radioactive drugs.

[0007] Accurately calculating the detection efficiency of the detector for the gamma-ray full-energy peak of the nuclide to be measured is a prerequisite for using CZT to measure the activity of radioactive drugs, and it is also a core parameter that affects the measurement results. General activity measurement devices can only measure activity under specific geometric conditions, specific solution containers, specific measurement parameters, etc., and cannot meet the needs of multiple clinical scenarios in nuclear medicine. Passive efficiency calibration technology is a measurement model of detectors and samples based on the Monte Carlo method. It can simulate and calculate the detection efficiency under any measurement conditions, and the calculation results are reliable. The passive efficiency calibration technology based on the Monte Carlo method is used in conjunction with a new gamma energy spectrum detector based on CZT to accurately measure the activity of radioactive drugs under various measurement conditions.

[0008] In addition to nuclear medicine 131 I. 99m Tc and other gamma-ray emitting nuclides (hereinafter referred to as gamma nuclides) are also widely used 18 F and other positron-emitting nuclides (hereinafter referred to as positron nuclides). The positrons emitted when the positron-emitting nuclides decay will only produce two 511keV gamma photons after being absorbed by the surrounding medium. However, if the energy of the positrons is large, some positrons will not annihilate near the detector and produce photons. Therefore, it is difficult to measure the detection efficiency by the standard source calibration method. For general activity measurement devices, if the absorption rate of positrons by the drug itself and the container is not taken into account, the measurement results will be biased, and the greater the energy of the emitted positrons, the greater the deviation. The Monte Carlo method can simulate the interaction process between positrons and matter, and the passive efficiency calibration technology is also applicable to the calculation of 18 Efficiency calculation of positron-emitting radiopharmaceuticals such as F. Summary of the invention

[0009] The present invention provides a radiopharmaceutical activity measurement device and method based on passive efficiency calibration, which can solve at least one of the above technical problems.

[0010] To achieve the above object, the present invention adopts the following technical solutions:

[0011] A radiopharmaceutical activity measuring device based on passive efficiency calibration includes a detector base, a CZT gamma spectrum detector, a sample tray, a sample holder, a stopper, a detector signal processing system, a data reader, data acquisition and analysis software, a display, and a passive efficiency calibration program, wherein:

[0012] The CZT γ spectrum detector is placed on the detector base;

[0013] The sample holder is fixed above the detector base;

[0014] A sample tray is horizontally arranged in the sample holder;

[0015] The sample tray is used for placing the radioactive solution container, and the radioactive solution is placed in the radioactive solution container.

[0016] Furthermore, a limiter is arranged in the bracket, and the sample tray is directly placed on the limiter.

[0017] Furthermore, the sample tray is made of a disc-shaped organic glass with a thickness of 2 mm and a diameter of 50 mm, and the disc is marked with a scale with the minimum unit being mm.

[0018] Furthermore, the CZT gamma energy spectrum detector uses a 10mm×10mm×5mm quasi-hemispherical detector, or a 5mm×5mm×2.5mm quasi-hemispherical detector.

[0019] Furthermore, the sample holder is made of cylindrical shell-shaped organic glass with a wall thickness of 5 mm, an inner diameter of 50 mm, a height of 50 mm, and a scale on the holder.

[0020] Furthermore, the sample holders have a total of 8 holders, which can be stacked on top of each other, so that the maximum height of the sample from the detector is 400 mm, and two holders can interlock naturally.

[0021] Furthermore, each sample holder has five stoppers inside, with a width of 2 mm and one stopper every 10 mm, and the stoppers are fixed with glue.

[0022] On the other hand, a method for measuring radiopharmaceutical activity based on passive efficiency calibration of the present invention adopts the above-mentioned radiopharmaceutical activity measuring device based on passive efficiency calibration, comprising the following steps:

[0023] S1. CZT detector working parameter debugging: by adjusting the working voltage, pulse shaping time and other parameters, the energy resolution, peak-to-peak and system dead time of the CZTγ spectrum detector can meet the set requirements;

[0024] S2. Characterization of CZT detectors: Use 241 Am, 152 Eu, 137 Cs, 60 The Co point standard source characterizes the detector, that is, by comparing the measured value of the detection efficiency with the simulated calculated value, the various parameters of the detector are continuously adjusted, and finally an efficiency calculation model that is in good agreement with the measured efficiency value is obtained, and this model is used as the input parameter of the passive efficiency calibration;

[0025] S3. Select the set measurement height: select a suitable distance so that the "dead time" of the test system is no more than 10% and the measurement result is more reliable;

[0026] S4. Measure the γ spectrum of radiopharmaceuticals: Under the set measurement height, measure the γ spectrum of the radiopharmaceutical sample until the full energy peak count reaches 10,000. At this time, the uncertainty of the full energy peak count is 1%;

[0027] S5. Select the radiopharmaceutical container type;

[0028] S6. Setting the radioactive drug container parameters: setting the parameters in the passive efficiency calibration program according to the drug container used in the measurement;

[0029] S7, setting the measurement height: setting the corresponding height in the passive efficiency calibration program according to the height during measurement;

[0030] S8. Set the sample position: according to the specific position during measurement, set the corresponding position in the passive efficiency calibration program and set the placement state at the same time;

[0031] S9. Calculate the efficiency value: Calculate the detection efficiency based on the set parameters and the energy of the characteristic gamma rays emitted by the radioactive drug; if the composite detection efficiency of the detector for positron nuclides is calculated, the energy spectrum of the positrons emitted by the positron nuclides is used as the input parameter of the passive efficiency calibration program;

[0032] S10, calculation results: if the gamma nuclide radiopharmaceutical is measured, the activity is calculated using the following formula (1); if the positron nuclide radiopharmaceutical is measured, the activity is calculated using the following formula (2);

[0033] Among them, when measuring the activity of γ-nuclides radiopharmaceuticals:

[0034] The nuclide that emits gamma rays when decaying is called a gamma nuclide. The gamma energy spectrum of the gamma nuclide radiopharmaceutical is measured using CZT, and the total energy peak count rate of the characteristic gamma rays is analyzed. The activity of the radiopharmaceutical is calculated according to the following formula (1):

[0035]

[0036] A: Sample activity

[0037] n: The total energy peak count rate of gamma rays with energy E, which can be obtained by analyzing the CZT gamma spectrum;

[0038] ε(E): detection efficiency of CZT for the full energy peak of gamma rays with energy E, calculated by simulation using the passive efficiency calibration method;

[0039] η: the emission rate of gamma rays with energy E emitted by the radionuclide, which can be obtained through the nuclear database;

[0040] When measuring the activity of positron-emitting nuclide radiopharmaceuticals:

[0041] The nuclide that emits positrons during decay is called a positron nuclide. The gamma energy spectrum of positron nuclide radiopharmaceuticals is measured using CZT, and the full energy peak count rate of 511keV gamma rays is analyzed. When a positron annihilates, two 511keV gamma rays are generated. Therefore, the activity of the radiopharmaceutical is calculated using the following formula (2):

[0042]

[0043] A: Positron nuclide sample activity

[0044] n 511 : The full energy peak count rate of gamma rays with an energy of 511keV,

[0045] ε 511 : The detection efficiency of CZT for the full energy peak of γ-rays with an energy of 511keV;

[0046] ɑ: positron annihilation rate, which is related to parameters such as the sample medium and the material thickness of the container;

[0047] η: Positron emission nuclide β + Probability of decay;

[0048] Among them, the full energy peak count rate n 511 The positron emission spectrum of CZT was obtained by analyzing the γ spectrum. + The probability of decay can be found through the decay diagram of the nuclide. 18 F, η is 96.86%; ε c =2·ε 511 ·ɑ is called the composite detection efficiency of the CZT detector for positron nuclides, which is calculated by simulation using the passive efficiency calibration method.

[0049] Furthermore, step S5 specifically includes selecting different types of containers such as cylindrical vials, water cups, and syringes in the passive efficiency calibration program according to the drug containers used in the measurement.

[0050] Furthermore, the radiopharmaceutical container parameters set in S6 include information such as the material, geometric shape, and thickness of the container.

[0051] It can be seen from the above technical solution that the radiopharmaceutical activity measurement device based on passive efficiency calibration of the present invention has the following beneficial effects:

[0052] The passive efficiency calibration technology based on the Monte Carlo method is used in conjunction with a new CZT-based gamma spectrum detector to accurately measure the activity of radiopharmaceuticals under various measurement conditions. It does not require the use of a standard source calibration detection system. It can distinguish the gamma energy spectra emitted by different nuclides, and can be used to measure the nuclide purity of radiopharmaceuticals, and can also monitor the radioactive contamination of the radiopharmaceuticals themselves and the operating site. It can not only measure 131 I. 99m For common radioactive drugs such as Tc, as long as the drug emits gamma rays, the activity can be measured by this device in theory. It can be measured by calculating the positron annihilation rate and the 511keV gamma ray full energy peak. 18 F. 15 O. 11 C. 13 The activity of positron-emitting radiopharmaceuticals such as N. The minimum detectable activity of radiopharmaceuticals is 10 2 Bq, the maximum measurable activity is 10 10 Bq. The uncertainty of the activity measurement result is about 4%. The present invention uses a new semiconductor CZTγ spectrum detector to record the γ rays emitted by radiopharmaceuticals and identify different nuclides through the γ-ray spectrum. In theory, the activity of radiopharmaceutical samples under any conditions can be measured according to clinical needs, without being restricted by the geometry and material of the radiopharmaceutical container, the volume of the radiopharmaceutical, the distance and relative position between the sample and the detector, and can meet the needs of multiple scenarios in the diagnosis and treatment of radiopharmaceuticals. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 HPGe, CZT, LaBr3(Ce), CeBr3 and NaI(Tl) are measured by the embodiments of the present invention. 152 Eu point source gamma spectrum;

[0054] Figure 2 is a schematic structural diagram of an embodiment of the present invention;

[0055] Figure 3 It is a physical diagram of the device of the example of the present invention;

[0056] Figure 4 It is a schematic diagram of the half-height width at different voltages;

[0057] Figure 5 It is a schematic diagram of the peak-to-compartment ratio at different voltages;

[0058] Figure 6 It is a schematic diagram of the relationship between forming time and FWHM;

[0059] Figure 7 It is a schematic diagram of the relationship between the forming time and the peak-to-compartment ratio;

[0060] Figure 8 It is a schematic diagram of the relationship between the forming time and the dead time of the signal processing of the electronic system;

[0061] Fig. 9 This is a comparison of the energy spectra of a series of monoenergetic gamma-ray sources measured by HPGe and CZT;

[0062] Fig.10 This is a schematic diagram of the CZT detector's edgeless efficiency calibration results and measured efficiency results;

[0063] Fig.11 It is measured by the device under different height conditions 131 I solution gamma spectrum;

[0064] Fig.12 It is measured by the device under different height conditions 99m Tc solution gamma spectrum;

[0065] Fig.13 yes 131 I. 99m Tc, 18 Gamma spectra of F radiopharmaceuticals;

[0066] Fig.14 It is a schematic diagram of the detection efficiency calculation model;

[0067] Fig.15 is the detection efficiency under different SD conditions;

[0068] Fig.16 It is the device's impurity identification capability measurement spectrum;

[0069] Fig.17 It is measured using the device 223 Energy spectrum of Ra radiopharmaceuticals;

[0070] Fig.18 Measured using the device 225 Ac(including the mother nucleus 229 Th) Energy spectrum of radiopharmaceuticals;

[0071] Fig.19 Device pair under different SD conditions 18 Calculation results of the composite detection efficiency of F. DETAILED DESCRIPTION

[0072] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments.

[0073] The radioactive drug activity measuring device based on passive efficiency calibration described in this embodiment includes a detector base 1, a CZTγ energy spectrum detector 2, a sample tray 3, a sample holder 4, a limiter 5, a detector signal processing system, a data reader, data acquisition and analysis software, a display, a passive efficiency calibration program, etc.; a radioactive solution container 6 is placed on the sample tray 3, and a radioactive solution 7 is placed in the radioactive solution container 6. Figure 2 is a schematic diagram of the structure of the device. Figure 3 This is a homemade photo of the real thing.

[0074] The CZT γ energy spectrum detector can use a 10mm×10mm×5mm quasi-hemispherical detector or a 5mm×5mm×2.5mm quasi-hemispherical detector.

[0075] The sample tray is made of a disc-shaped organic glass with a thickness of 2mm and a diameter of 50mm, and can be placed directly on the stopper. The disc is marked with a scale with the minimum unit of mm.

[0076] The sample holder is made of cylindrical plexiglass with a wall thickness of 5mm, an inner diameter of 50mm, and a height of 50mm. There are scales on the holder. There are 8 holders in total, which can be stacked on top of each other, so that the maximum height of the sample from the detector is 400mm, and the two holders can fit together naturally.

[0077] Stopper: Each sample holder has 5 stoppers inside, with a width of 2mm and one stopper every 10mm. The stoppers can be fixed with glue. The sample can be measured at any height between 0-400mm and every 10mm.

[0078] The steps of using the embodiment of the present invention are as follows:

[0079] 1. CZT detector working parameter debugging: By adjusting the working voltage, pulse shaping time and other parameters, the energy resolution of the CZTγ spectrum detector is the best, the peak-to-voltage ratio is large, and the dead time of the system is short.

[0080] 2. Characterization of CZT detectors: Use 241 Am, 152 Eu, 137 Cs, 60 The Co point standard source characterizes the detector, that is, by comparing the measured value of the detection efficiency with the simulated calculated value, the various parameters of the detector are continuously adjusted, and finally an efficiency calculation model that is in good agreement with the measured efficiency value is obtained, and this model is used as the input parameter of the passive efficiency calibration.

[0081] 3. Choose a suitable measurement height: The activity of radioactive drugs used in clinical applications is often relatively large. If the sample is too close to the detector, the system's "dead time" will be very large, the spectrum will be distorted, and the total energy peak count calculation will be inaccurate. If the sample is too far away from the detector, the counting rate will be low and the measurement time will be longer. Therefore, it is necessary to choose a suitable distance. After testing, the "dead time" of the system is not more than 10%, and the measurement result is more reliable. The distance between the detector and the sample in the activity measurement device can be adjusted. Place the sample to be tested at different distances from the detector to quickly measure the energy spectrum, observe the "dead time" indication of the detection system, and ensure that the "dead time" indication is less than 10%, and the counting rate can meet the requirements.

[0082] 4. Measure the gamma energy spectrum of radioactive drugs: Under the set measurement height conditions, measure the gamma energy spectrum of the radioactive drug sample and make the full energy peak count reach 10,000. At this time, the uncertainty of the full energy peak count is 1%.

[0083] 5. Select the type of radioactive drug container: According to the drug container used in the measurement, select different types of containers such as cylindrical vials, water cups, syringes, etc. in the passive efficiency calibration program.

[0084] 6. Set the radioactive drug container parameters: Set the parameters in the passive efficiency calibration program according to the drug container used in the measurement, including the container's material, geometry, thickness and other information.

[0085] 7. Set the measurement height: Set the corresponding height in the passive efficiency calibration program according to the height during measurement.

[0086] 8. Set the sample position: According to the specific position during measurement, set the corresponding position in the passive efficiency calibration program, and set the placement state at the same time, for example, the angle between the syringe and the detector axis when it is placed horizontally.

[0087] 9. Calculate the efficiency value: Calculate the detection efficiency based on the set parameters and the energy of the characteristic gamma rays emitted by the radiopharmaceutical. If the composite detection efficiency of the detector for positron nuclides is calculated, the energy spectrum of the positrons emitted by the positron nuclides must also be used as the input parameter of the passive efficiency calibration program.

[0088] 10. Calculation results: If a gamma nuclide radiopharmaceutical is measured, the activity is calculated using the following formula (1). If a positron nuclide radiopharmaceutical is measured, the activity is calculated using the following formula (2).

[0089] The measurement principle of the embodiment of the present invention is as follows:

[0090] 1. Principle of gamma nuclide radiopharmaceutical activity measurement

[0091] The nuclide that emits gamma rays when decaying is called a gamma nuclide. Use CZT to measure the gamma spectrum of gamma nuclide radiopharmaceuticals, analyze the total energy peak count rate of characteristic gamma rays, and calculate the activity of the radiopharmaceutical according to the following formula:

[0092]

[0093] A: Sample activity

[0094] n: The total energy peak count rate of gamma rays with energy E, which can be obtained by analyzing the CZT gamma spectrum.

[0095] ε(E): detection efficiency of CZT for the full energy peak of gamma rays with energy E, calculated using the passive efficiency calibration method.

[0096] η: The emission rate of gamma rays with energy E emitted by the radionuclide, which can be obtained through the nuclear database.

[0097] 2. Principle of activity measurement of positron-emitting nuclide radiopharmaceuticals

[0098] The nuclides that emit positrons when decaying are called positron nuclides. Use CZT to measure the gamma spectrum of positron nuclide radiopharmaceuticals and analyze the full energy peak count rate of 511keV gamma rays. When a positron annihilates, two 511keV gamma rays are generated. Therefore, the activity of the radiopharmaceutical can be calculated using the following formula:

[0099]

[0100] A: Positron nuclide sample activity

[0101] n 511 : The full energy peak count rate of gamma rays with an energy of 511keV,

[0102] ε 511 :Detection efficiency of CZT for the full energy peak of γ-rays with energy of 511keV

[0103] ɑ: Positron annihilation rate, which is related to parameters such as the sample medium and the material thickness of the container

[0104] η: Positron emission nuclide β + Probability of decay

[0105] Among them, the full energy peak count rate n 511 It can be obtained by analyzing the γ spectrum measured by CZT, and the positron nuclide generates β + The probability of decay can be found through the decay diagram of the nuclide. 18 F,η is 96.86%. ε c =2·ε 511·ɑ is called the composite detection efficiency of the CZT detector for positron nuclides, which is calculated by simulation using the passive efficiency calibration method.

[0106] Measurement Examples

[0107] 1. CZT working parameter debugging

[0108] In order to test the optimal working voltage of CZT, the CZT detector was used to measure the 137 Cs point source, and calculate the half-maximum width (FWHM) of the 661.77keV gamma-ray full energy peak. The results are shown in Figure 4 , the peak-to-combustion ratio under different operating voltages was also calculated, and the results are shown in Figure 5 This device uses the DT-01C11005 type 10×10×5mm produced by Ditech. 3 Quasi-hemispherical CZT detector.

[0109] Depend on Figure 4 It can be seen that for the DT-01C11005 CZT detector, when the operating voltage is less than 700 V, the energy resolution gradually improves with the increase of voltage, but when the voltage exceeds 700 V, the half-width (FWHM) of the 661.77 keV gamma-ray full-energy peak remains basically unchanged when the voltage is further increased.

[0110] Depend on Figure 5 It can be seen that the peak-to-compton ratio of the CZT detector gradually increases with the increase of the operating voltage. However, when the operating voltage increases to 900V, the peak-to-compton ratio remains basically unchanged.

[0111] According to the above test data, the optimal operating voltage of this DT-01C11005 quasi-hemispherical CZT detector is about 900V.

[0112] In order to test the optimal pulse shaping time of the device, the CZT detector was used to measure the pulses at different shaping times. 137 Cs point source, and calculate the half-maximum width (FWHM) of the 661.77keV gamma-ray full energy peak. The results are shown in Figure 6 The peak-to-compartment ratio and system dead time at different pulse shaping times were also recorded. The results are shown in Figure 7 and Figure 8 .

[0113] Depend on Figure 6-Figure 8It can be seen that the longer the pulse shaping time is, the greater the dead time of the detection system is. A large dead time is not conducive to measurement, but the shaping time is related to the energy resolution of the detection system, so it is necessary to select an appropriate shaping time. When the pulse shaping time of the CZT detector is 2.4μs, the FWHM of the 661.77keV γ-ray full-energy peak is the smallest. A larger peak-to-Compton ratio is beneficial to measurement. The larger the pulse shaping time, the larger the peak-to-Compton ratio. However, after the shaping time reaches 2μs, the peak-to-Compton ratio changes very slowly with the shaping time. The larger the shaping time, the greater the dead time of the electronic system. A large dead time is not conducive to measurement. Based on the above test data, it is more appropriate to set the shaping time at 2.4μs. Therefore, the optimal working parameters of CZT are an operating voltage of 900V and a pulse shaping time of 2.4μs. In order to compare the energy spectrum measurement effect of this device, a series of monoenergetic γ-nuclides standard sources (including 241 Am, 109 Cd, 57 Co. 139 Ce, 51 Cr, 113 Sn, 85 Sr. 137 Cs, 54 Mn and 65 Zn), the measured energy spectrum is shown in Fig. 9 .

[0114] 2. Characterization of CZT Detectors

[0115] By using 241 Am, 137 Cs, 60 Co and 152 Eu point source characterization of CZT detector, Fig.10 The maximum relative deviation between the efficiency curve calculated by simulation and the measured values ​​is 5%.

[0116] 3. Choice of measurement height

[0117] If the activity of the sample being measured is very high, the detector count rate will be very high, which will increase the detector's "dead time" and affect the accuracy of the measurement results. Therefore, when the activity of the radioactive drug used in clinical practice is relatively high, the detector's "dead time" can be reduced by increasing the distance between the sample and the detector (hereinafter referred to as "SD"). After testing, the detector's "dead time" is no more than 10%, and the impact on the measurement results can be ignored. Fig.11 It is 8.89×10 measured under different SD conditions. 7 Bq 131 I solution gamma spectrum, Fig.12 It is 6.86×10 measured under different SD conditions. 7 Bq 99m γ spectrum of Tc solution. It can be seen that when the SD is small, the peak shape in the γ spectrum is distorted and the total energy peak count will have a large deviation.

[0118] 4. Measuring the gamma spectrum of radiopharmaceuticals

[0119] The device was used to measure 131 I. 99m Tc, 18 Gamma spectra of radiopharmaceuticals such as F are shown in Fig.13 .

[0120] 5. Select the type of radiopharmaceutical container

[0121] According to the actual clinical situation, 20×40mm glass bottles and 25×45mm plastic bottles were selected to hold radioactive drugs. 5mL syringes were also used.

[0122] 6. Setting Radiopharmaceutical Container Parameters

[0123] Ф20×40mm cylindrical glass bottle container, wall thickness 1mm, density 2.5g / cm 3 Glass, Ф25×45mm cylindrical plastic bottle container with a wall thickness of 1mm and a density of 0.98g / cm 3 of plastic.

[0124] 7. Set the measurement height

[0125] According to the measurement needs, the distance from the sample to the CZT detector surface (distance from Source to Detector, hereinafter referred to as "SD") was set respectively, and nine measurement heights of SD=0, SD=39mm, SD=89mm, 139mm, 189mm, 239mm, 289mm, 339mm and 389mm were set.

[0126] 8. Set the sample position

[0127] The containers containing radioactive drugs are placed on the central axis of the CZT detector. The cylindrical containers are placed vertically and the syringes are placed horizontally.

[0128] 9. Calculate efficiency value

[0129] The detection efficiency of CZT for the full energy peak of γ-rays of radiopharmaceuticals in Ф20×40mm glass bottles was calculated under the conditions of SD=0, 39mm, 89mm, 139mm, 189mm, 239mm, 289mm, 339mm and 389mm. The calculation model is shown in Fig.14 , the efficiency calculation results are shown in Fig.15 .

[0130] 10. Calculation results

[0131] (1) Accuracy of device measurement results

[0132] a. Measurement results of samples with different activities

[0133] The reference activities measured using this device were 4.44×10 6 Bq, 4.44×10 5 Bq, 4.44×10 4 Bq and 4.44×10 2 Bq 131 I solution sample, the measured reference activity was 6.86×10 6 Bq, 6.86×10 5 Bq, 6.86×10 4 Bq and 6.86×10 2 Bq 99m Tc solution sample, the measurement results are shown in Table 3 and Table 4.

[0134] Table 3 Different device measurements 131 Results for I activity samples

[0135]

[0136] Table 4 Device measurement is different 99m Results for Tc activity samples

[0137]

[0138]

[0139] The results in the table show that the use of the device and passive calibration technology can accurately measure the activity of radioactive drugs within 10 7 Bq to 10 2 The deviation between the activity measurement results and the reference value between Bq is small, with the maximum value not exceeding -4.7%.

[0140] b. Measurement results of different drug containers

[0141] In order to understand the influence of different containers on the measurement results, 20×40 mm glass bottles and 25×45 mm plastic bottles were selected to hold the same volume and activity of 131 I solution and 99m Tc solution, the activity was measured using the device, and the results are shown in Table 5.

[0142] Table 5 Measurement results of radiopharmaceuticals in different containers

[0143]

[0144] From the measurement results in Table 5, it can be seen that the deviations between the sample activities in different containers obtained by using the device to measure radioactive drugs and the reference activities in combination with the passive efficiency calibration technology are no more than 3.4%. In theory, this method is applicable to any container.

[0145] c. Measurement results of different volumes

[0146] In order to understand the effect of the volume of solution (liquid level) in the container on the measurement results, take a small amount of 131 I or 99m Tc chemical was dropped into a 20×40mm glass bottle, and deionized water was added into the bottle to make the distance between the liquid level and the bottom 7mm, and then the prepared sample was placed on the sample tray for measurement (SD=89mm). After the measurement, deionized water was added into the bottle again to make the distance between the liquid level and the bottom 14mm, and then the prepared sample was placed on the sample tray for measurement. The operation was repeated until the liquid level was 34mm, and thus the energy spectra of liquid heights H=7mm, H=14mm, H=21mm, H=28mm and H=34mm were obtained. The results are shown in Table 6.

[0147] Table 6 Measurement results of different volume solutions

[0148]

[0149] It can be seen from Table 6 that the deviation between the activity values ​​of radionuclides in different volumes of aqueous solution obtained using the device and passive calibration technology and the reference value is very small, with the maximum not exceeding -4.5%. Therefore, it is applicable to solution devices of any height.

[0150] (2) Minimum measurable activity of the device

[0151] The low activity with a reference activity of 889 Bq was measured using this device. 131 I solution and a low activity reference of 686 Bq 99m Tc solution, the measurement results are shown in Table 7.

[0152] Table 7 Measurement results of low activity samples by the device

[0153] Measurement results <![CDATA[ 131 I]]> <![CDATA[ 99m Tc]]> Activity (Bq) 926.3 664.7 Relative deviation from reference activity 4.2％ 3.2％

[0154] According to the measurement results, the device can accurately measure radioactive drugs with an activity of only a few hundred Bq. 131 The deviation of the I measurement result from the reference value is 4.2%. 99mThe deviation of the Tc measurement result from the reference value is 3.2%. If a longer measurement time or a larger CZT detector is used, the minimum measurement activity can be reduced.

[0155] (3) Maximum measurable activity of the device

[0156] Measuring higher activity radioactive drugs can be achieved by increasing SD or reducing the volume of CZT. In practical applications, SD cannot be increased indefinitely, and a maximum of 40 cm is acceptable. However, increasing SD further will require a lot of space, which is not very practical. It is more practical to use a smaller CZT detector to measure high activity radioactive drugs. After testing, when SD = 40, using 5×5×2.5mm 3 The quasi-hemispherical CZT detector can measure the maximum activity of 7.4×10 9 If a smaller CZT detector is used or the SD is increased, radioactive drugs with a higher activity can be measured. Theoretically, the activity can be 10 11 Bq (several Ci) of radioactive drug.

[0157] (4) Measurement rate of the device

[0158] In order to determine the measurement rate of the device, the reference activity of 8.89×10 7 Bq 131 I and 6.86×10 7 Bq 99m Tc solution. When the full energy peak count reaches 10000, the relative standard deviation caused by the detector count is 1%, and when the full energy peak count reaches 1000, the relative standard deviation is 3.2%. In order to ensure the reliability of the measurement results, the full energy peak ( 131 I: 364keV full energy peak, 99m Tc: 140keV full energy peak) counts all exceeded 10,000, and the time t required for the peak area to reach 10,000 was recorded. 10000 The results are shown in Table 8.

[0159] Table 8 t of the device under different SD conditions 10000 Measurement results

[0160] Distance between sample and detector <![CDATA[ 131 I]]> <![CDATA[ 99m Tc]]> SD=89mm 2.6 0.6 SD=139mm 5.8 1.3 SD=189mm 10.0 2.4 SD=239mm 14.3 3.6 SD=289mm 21.5 5.0 SD=339mm 28.8 6.7 SD=389mm 35.9 9.1

[0161] It can be seen that the device can obtain the 131 The measurement result of I can be obtained in 0.6 seconds 99m The relative standard deviation of the Tc measurement results was less than 1%.

[0162] (5) The device’s ability to identify impurity nuclides

[0163] In order to test the device's ability to identify impurity nuclides, four different activity 131 I and 99m The Tc mixed solution samples were all packed in plastic vials of 25×45 mm in diameter, with a volume of 10 ml. Sample 1 was 99m Tc(3.43×10 5 Bq)+ 131 I(8.89×10 2 Bq), the spectrum measurement time is 1336s; sample 2 is 99m Tc(1.72×10 5 Bq)+ 131 I(8.89×10 6 Bq), the spectrum measurement time is 386s; sample 3 is 99m Tc(1.72×10 5 Bq)+ 131 I(4.45×10 5 Bq), the energy spectrum measurement time is 227s; sample 4 is 99m Tc(3.43×10 6 Bq)+ 131 I(8.89×10 3 Bq), the energy spectrum measurement time is 351s. The energy spectrum of each sample measured by CZT is shown in Fig.16 .

[0164] It can be seen from the measured energy spectrum that if 99m Tc is mixed with a small amount of 131 I, even if the activity of two nuclides differs by three orders of magnitude, they can be clearly identified in the energy spectrum. The ability of the device to identify impurity nuclides is related to its minimum detectable activity. If time permits, 10 6 Bq contains 10 1 Bq level 131 I identified it.

[0165] (6) New radionuclide capabilities

[0166] 223 Ra and 225 Ac is a new type of radiopharmaceutical. 223 Ra has just been approved for clinical use in my country. 225 Ac is still in the clinical trial stage internationally. 223 Ra and 225 Ac(including the mother nucleus 229The deviation between the measured results and the reference activity is no more than 3%. Fig.17 It is measured using the device 223 Energy spectrum of Ra radiopharmaceuticals, Fig.18 It is measured using the device 225 Ac(including the mother nucleus 229 Th) Energy spectrum of radiopharmaceuticals.

[0167] (7) Measurement of positron nuclides

[0168] The passive efficiency calibration program was used to calculate the 10×10×5mm 3 CZT detector pair 18 The composite detection efficiency of F was calculated under the conditions of SD = 0, 39, 89, 139, 189, 239 and 289 mm. The calculation condition is 10 ml 18 The F solution was placed in a glass bottle with a diameter of 20 × 40 mm and a wall thickness of 1 mm. The efficiency calculation results are shown in Fig.19 , 18 The results of F activity measurements are shown in Table 9.

[0169] Table 9 18 F activity concentration results

[0170]

[0171] It can be seen from Table 9 that under different SD conditions, 18 The average value of the measured F activity concentration is 1.11×10 9 Bq, with a reference activity of 1.10×10 9 Bq, the deviation is no more than 1%. The maximum relative deviation between the measured value and the average value under different SD conditions is 3.6%.

[0172] (8) Uncertainty analysis of device measurement results

[0173] According to formula (1) and formula (2), the uncertainty of the measurement result mainly comes from the uncertainty of the total energy peak count rate of the sample and standard source, the uncertainty of the reference activity of the standard source and the uncertainty of the gamma-ray emission rate. The net counts of the total energy peak of the sample and the standard source gamma-ray are both over 10,000, the uncertainty of the count rate will not be greater than 1%, the uncertainty of the gamma-ray emission rate is 1%, and the uncertainty of the standard source activity is calculated as 3%. Therefore, the uncertainty of the measurement result of the CZT activity measurement device will not be greater than 4%.

[0174] In summary, the passive efficiency calibration technology based on the Monte Carlo method in the embodiment of the present invention is used in conjunction with a new gamma spectrum detector based on CZT to accurately measure the activity of radiopharmaceuticals under various measurement conditions. There is no need to use a standard source calibration detection system. The gamma energy spectra emitted by different nuclides can be distinguished, which can be used to measure the nuclide purity of radiopharmaceuticals, and can also monitor the radioactive contamination of the radiopharmaceuticals themselves and the operating site. It can not only measure 131 I. 99m For common radioactive drugs such as Tc, as long as the drug emits gamma rays, the activity can be measured by this device in theory. It can be measured by calculating the positron annihilation rate and the 511keV gamma ray full energy peak. 18 F. 15 O. 11 C. 13 The activity of positron-emitting radiopharmaceuticals such as N. The minimum detectable activity of radiopharmaceuticals is 10 2 Bq, the maximum measurable activity is 10 10 Bq. The uncertainty of the activity measurement result is about 4%. Theoretically, the activity of radiopharmaceutical samples under any conditions can be measured according to clinical needs, without being restricted by the geometry and material of the radiopharmaceutical container, the volume of the radiopharmaceutical, the distance and relative position between the sample and the detector, and can meet the needs of multiple scenarios in the diagnosis and treatment of radiopharmaceuticals.

[0175] use 131 I and 99m The performance of the commonly used activity meter and this device were tested for Tc radiopharmaceuticals. The performance parameters of this device were compared with those of the commonly used activity meters. The results are shown in Table 1.

[0176] Table 1 Comparison of performance parameters of activity meter and device

[0177]

[0178] The energy resolution of the γ-ray spectrum measurement equipment is an important indicator for measuring the activity of nuclides. Figure 1 This device (CZT) is used to measure 152 The energy resolution of Eu point source is compared with the common HPGe, NaI(Tl), LaBr3(Ce) and CeBr3 γ spectrum measurement equipment. Table 1 lists the energy resolution of this equipment and HPGe, NaI(Tl), LaBr3(Ce), CeBr3 241 Am, 137 Cs and 60 The full-energy half-width (FWHM) of the characteristic gamma-ray emitted by Co.

[0179] Table 2 FWHM of the full energy peak of gamma rays of different energies for various detectors

[0180]

[0181] from Figure 1 It can be seen from Table 2 that the resolution of the device for the full energy peaks of gamma rays of different energies is second only to HPGe, and better than the energy resolution of LaBr3(Ce), CeBr3 and NaI(Tl).

[0182] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A radiopharmaceutical activity measuring device based on passive efficiency calibration, comprising a detector base, a CZTγ spectrum detector, a sample tray, a sample holder, and a stopper, characterized in that: The CZT γ spectrum detector is placed on the detector base; The sample holder is fixed above the detector base; A sample tray is horizontally arranged in the sample holder; The sample tray is used for placing a radioactive solution container, and the radioactive solution is placed in the radioactive solution container; It also includes setting a stopper in the bracket, and placing the sample tray directly on the stopper; The sample holder has 8 holders in total, which can be stacked one on top of the other, so that the maximum height of the sample from the detector is 400 mm, and two holders can be naturally interlocked.

2. The radiopharmaceutical activity measuring device based on passive efficiency calibration according to claim 1, characterized in that: The sample tray is made of a disc-shaped organic glass with a thickness of 2 mm and a diameter of 50 mm. The disc is marked with a scale with the minimum unit being mm.

3. The radiopharmaceutical activity measuring device based on passive efficiency calibration according to claim 1, characterized in that: The CZT γ energy spectrum detector uses a 10mm×10mm×5mm quasi-hemispherical detector, or a 5mm×5mm×2.5mm quasi-hemispherical detector.

4. The radiopharmaceutical activity measuring device based on passive efficiency calibration according to claim 1, characterized in that: The sample holder is made of cylindrical organic glass with a wall thickness of 5 mm, an inner diameter of 50 mm, and a height of 50 mm. There are scales on the holder.

5. The radiopharmaceutical activity measuring device based on passive efficiency calibration according to claim 1, characterized in that: Each sample holder has five stoppers inside, with a width of 2 mm and one stopper every 10 mm. The stoppers are fixed with glue.

6. A method for measuring radiopharmaceutical activity based on passive efficiency calibration, using the radiopharmaceutical activity measuring device based on passive efficiency calibration according to any one of claims 1 to 5, characterized in that: The following steps are included: S1. CZT detector working parameter debugging: By adjusting the working voltage, pulse shaping time and other parameters, the energy resolution, peak-to-peak and system dead time of the CZTγ spectrum detector can meet the set requirements; S2. Characterization of CZT detectors: Use 241 Am, 152 Eu, 137 Cs, 60 The Co point standard source characterizes the detector, that is, by comparing the measured value of the detection efficiency with the simulated calculated value, the various parameters of the detector are continuously adjusted, and finally an efficiency calculation model that is in good agreement with the measured efficiency value is obtained, and this model is used as the input parameter of the passive efficiency calibration; S3. Select the set measurement height: select a suitable distance so that the "dead time" of the test system is no more than 10%, and the measurement result is more reliable; S4. Measure the gamma spectrum of radiopharmaceuticals: Under the set measurement height, measure the gamma spectrum of the radiopharmaceutical sample and make the full energy peak count reach 10,000. At this time, the uncertainty of the full energy peak count is 1%. S5. Select the radiopharmaceutical container type; S6. Setting the radioactive drug container parameters: setting the parameters in the passive efficiency calibration program according to the drug container used in the measurement; S7, setting the measurement height: setting the corresponding height in the passive efficiency calibration program according to the height during measurement; S8. Set the sample position: according to the specific position during measurement, set the corresponding position in the passive efficiency calibration program and set the placement state at the same time; S9, calculate efficiency value: calculate detection efficiency according to the set parameters and the energy of characteristic gamma rays emitted by radioactive drugs; If the composite detection efficiency of the detector for positron nuclides is calculated, the energy spectrum of positrons emitted by the positron nuclides is used as the input parameter of the passive efficiency calibration program; S10. Calculation results: If a gamma nuclide radiopharmaceutical is measured, the activity is calculated using the following formula (1); if a positron nuclide radiopharmaceutical is measured, the activity is calculated using the following formula (2); Among them, when measuring the activity of γ-nuclides radiopharmaceuticals: The nuclide that emits gamma rays when decaying is called a gamma nuclide. The gamma energy spectrum of the gamma nuclide radiopharmaceutical is measured using CZT, the total energy peak count rate of the characteristic gamma rays is analyzed, and the activity of the radiopharmaceutical is calculated according to the following formula (1): (1) A: Sample activity n: γ-ray full energy peak count rate with energy E, obtained by analyzing the CZT γ spectrum; ɛ(E): detection efficiency of CZT for the full energy peak of gamma rays with energy E, calculated by simulation using the passive efficiency calibration method; η: the emission rate of gamma rays with energy E emitted by the radionuclide, which can be obtained through the nuclear database; When measuring the activity of positron-emitting nuclide radiopharmaceuticals: The nuclide that emits positrons during decay is called a positron nuclide. The gamma energy spectrum of positron nuclide radiopharmaceuticals is measured using CZT, and the full energy peak count rate of 511keV gamma rays is analyzed. When a positron annihilates, two 511keV gamma rays are generated. Therefore, the activity of the radiopharmaceutical is calculated using the following formula (2): (2) A: Positron nuclide sample activity n 511 : The full energy peak count rate of gamma rays with an energy of 511keV, ɛ 511 : The detection efficiency of CZT for the full energy peak of γ-rays with an energy of 511keV; ɑ: positron annihilation rate, which is related to parameters such as the sample medium and the material thickness of the container; η: Positron emission nuclide β + Probability of decay; Among them, the full energy peak count rate n 511 The positron emission spectrum of CZT was obtained by analyzing the γ spectrum. + The probability of decay can be found through the decay diagram of the nuclide. 18 F,η is 96.86%; c =2·ɛ 511 ·ɑ is called the composite detection efficiency of the CZT detector for positron nuclides, which is calculated by simulation using the passive efficiency calibration method.

7. A method for measuring radiopharmaceutical activity based on passive efficiency calibration according to claim 6, characterized in that: Step S5 specifically includes selecting different types of containers such as cylindrical vials, water cups, and syringes in the passive efficiency calibration program according to the drug containers used in the measurement.

8. A method for measuring radiopharmaceutical activity based on passive efficiency calibration according to claim 6, characterized in that: The radiopharmaceutical container parameters set in S6 include information such as the material, geometric shape, and thickness of the container.

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