A determination 90 Y glass microsphere radioactivity method

Abstract

The present invention discloses a method for determining 90 The method for measuring the radioactivity of Y glass microspheres comprises the following steps: 1) 90 Y glass microspheres are mixed with a flux and melted; 2) the melt is cooled to room temperature and an acidic solution is added to dissolve the melt to form a solution; 3) the solution is diluted with water and a sample is taken to determine the absolute activity of the solution. 90 Activity of Y; 4) Establish the 90 Y activity and 90 Transfer relationship of Y glass microsphere activity; 5) a series of different masses 90 Place the Y glass microspheres in the activity meter and measure the calibration factor curve of the activity meter; 6) weigh the sample to be measured 90 The mass of Y glass microspheres was measured using a calibrated activity meter. 90 The radioactivity of Y glass microspheres. 90 Y standard source or solution under the conditions of 90 Y glass microsphere products can measure the radioactivity quickly and accurately, are easy to operate, have high measurement accuracy, and are low in cost, making them suitable for actual production and clinical applications.

Description

Technical Field

[0001] The present invention relates to the field of radioactive analysis and measurement, and in particular to a 90 Y glass microsphere radioactivity measurement. Background Art

[0002] 90 Y microsphere embolization is an emerging non-surgical treatment method that combines interventional therapy and local radiotherapy. Clinical applications have shown that it has broad prospects in the treatment of internal radiation liver segment / lobe resection, transitional / downgrade treatment before liver transplantation, liver cancer recurrence after liver resection, and palliative treatment of mid- to late-stage liver cancer. 90 Y microsphere products can be divided into resin microspheres, glass microspheres, carbon microspheres, etc. 90 Y glass microspheres have high specific activity, 90 Y has the advantages of low dissolution rate and slight embolic effect, and has broad application prospects. 90 The accuracy of activity measurement is an important parameter of Y microsphere products and is closely related to the safety and effectiveness of clinical medication. If the activity measurement result is too low, more glass microspheres will be injected into the patient, which will not only easily lead to ectopic embolism due to reflux, but also the actual dose will be too high to cause radiation damage to normal tissues; if the activity measurement result is too high, the number of microspheres injected will be too small, and the expected treatment effect cannot be achieved. Therefore, a new method is established. 90 The accurate measurement method of Y microsphere activity 90 Accurate packaging, quality inspection, and back-end clinical drug delivery safety of Y glass microspheres are crucial.

[0003] because 90 Due to the special form of Y microsphere products, it is very difficult to accurately measure its activity. The main reasons are as follows: (1) 90 Y microsphere products are heterogeneous solutions, and the active ingredients are solid, with high density and deposited at the bottom of the bottle. Direct measurement will be affected by the self-absorption of the microspheres themselves; (2) 90 Y is a pure beta nuclide, and the signal obtained by the commonly used activity meter is not from 90 The β particles emitted by the Y nuclide itself are not β particles, but bremsstrahlung photons generated by the interaction of β particles with the medium and packaging materials. Therefore, the measurement results are closely related to external factors such as the medium in which the nuclide is located, the volume of the medium, the material and thickness of the packaging bottle; (3) 90 The half-life of Y is as short as 64 hours, and the microsphere product is a non-homogeneous phase, making it difficult to find a corresponding standard source to calibrate the activity meter.

[0004] Existing literature and patents on how to measure 90 The activity of Y microspheres was initially explored, such as Kelley M. Ferreira reported using a secondary standard ionization chamber system to measure 90 The activity of Y resin microspheres and the use of90 Y standard solution is used to calibrate the ionization chamber and improve the accuracy of measurement (Appl Radiat Isot, 2016, 109, 226–230.); V. Lourenco et al. reported that a mixed solution of hydrogen peroxide and divalent iron ions was used to dissolve the Fenton reaction. 90 Y resin microspheres and the triple double coincidence counting (TDCR) method was used to measure the activity of the dissolved solution (Appl Radiat Isot, 2015, 97, 170–176.); C. Thiam reported the use of a well-type ionization chamber to measure 90 The activity of Y resin microspheres was studied. The influence of different resin microsphere geometric conditions on the measurement response of the well-type ionization chamber was calculated through Monte Carlo simulation to improve the measurement accuracy (Appl Radiat Isot, 2016, 109, 231–235.).

[0005] The existing technology has the following shortcomings: the existing technology mainly focuses on 90 The exploration of the measurement method of Y resin microsphere activity, using the ionization chamber system to directly measure the activity of resin microspheres, the measurement results will be affected by the self-absorption of the microspheres themselves, and it is necessary to use standard 90 Y solution is used to calibrate the ionization chamber, and the measurement results are corrected by combining theoretical simulation. This method is complicated to operate and has low accuracy, which limits the practicality of the existing technology. The resin microspheres are dissolved by Fenton reaction and then the activity of the solution is measured. This method has a violent reaction process, many steps, and complicated operation. It is only applicable to polymer materials such as resins and is not suitable for 90 Y glass microspheres are composed of Y2O3, Al2O3, and SiO2. The solubility of the three is different. In the preparation process, the glass microspheres are treated at a high temperature of 1500-1600℃. The whole is completely vitrified, and γ-Al2O3 is completely converted into α-Al2O3, i.e. corundum, which is insoluble in acid and alkali. Therefore, the existing technology cannot achieve 90 The dissolution of Y glass microspheres cannot be achieved 90 Accurate measurement of Y glass microsphere activity. Summary of the Invention

[0006] In order to overcome the above-mentioned drawbacks, the present invention provides a method for measuring 90 Y glass microsphere radioactivity method. The present invention is applicable to 90 Y glass microsphere products can measure the radioactivity quickly and accurately, are easy to operate, have high measurement accuracy, and are low in cost, making them suitable for actual production applications.

[0007] A determination of the present invention 90 The method for measuring the activity of Y glass microspheres specifically includes:

[0008] (1) 90The Y glass microspheres are mixed and melted with a flux to form a melt;

[0009] (2) After the melt is cooled to room temperature, an acidic solution is added to dissolve the melt to form a solution;

[0010] (3) Add water to dilute the solution and make it constant. Take a sample and use the absolute activity measurement method to determine the content of the solution. 90 Activity of Y;

[0011] (4) Establish solution 90 Y activity and 90 The transfer relationship of Y glass microsphere activity is calculated to obtain a series of different mass M i of 90 Y The true activity of glass microspheres, where i = 1, 2, 3, ... N;

[0012] (5) A series of different qualities 90 Place Y glass microspheres into the activity meter, compare the actual activity with the measured value of the activity meter, determine the calibration factor curve of the activity meter, and calibrate the activity meter;

[0013] (6) Weigh the test piece 90 The mass of Y glass microspheres was measured using a calibrated activity meter. 90 Radioactivity of Y glass microspheres.

[0014] Optionally, the flux and 90 The mass ratio of Y glass microspheres is 3:1 to 100:1.

[0015] Optionally, the flux comprises anhydrous sodium carbonate and boric acid. Preferably, the mass ratio of the anhydrous sodium carbonate to boric acid is 1:1 to 10:1.

[0016] Optionally, the melting temperature is 800° C. to 1500° C., and the melting time is 20 min to 120 min.

[0017] Optionally, the mass volume ratio of the melt to the nitric acid solution is ≤50 g / L.

[0018] Optionally, the acidic solution is a nitric acid solution, and the concentration of the nitric acid solution is 0.5M to 3M.

[0019] Optionally, the nitric acid concentration of the solution after dilution with water is ≤1M to prevent the subsequent liquid scintillation determination of the dilution solution. 90 Y activity when precipitation occurs.

[0020] Optionally, the determination 90 The absolute activity of Y solution is measured by liquid scintillation CIEMAT / NIST method or 4πβ-γ coincidence measurement method. The liquid scintillation CIEMAT / NIST method uses tritium ( 3H) or carbon ( 14 C) Liquid scintillation standard solution was used for efficiency tracing, and the 90 The accurate activity of Y. The 4πβ-γ coincidence measurement method uses cobalt ( 60 Co) standard solution was used for efficiency tracing and coincidence counting to obtain 90 The exact activity of Y.

[0021] The solution 90 Y activity and 90 The transfer relationship of Y glass microsphere activity is: 90 The mass specific activity of Y glass microspheres is determined by accurate weighing. 90 The quality of Y glass microspheres is gently and non-destructively digested and accurately measured after digestion. 90 The activity of solution Y gives the unit mass 90 The activity of Y glass microspheres is the mass specific activity, which is used to establish the 90 Y activity to 90 Y glass microsphere activity transfer.

[0022] The activity meter is a well-type ionization chamber. 90 Y glass microspheres are used as a standard source to calibrate the ionization chamber under specific geometric conditions, and a calibration factor curve is obtained between the actual activity of glass microspheres under different mass conditions and the measured value of the activity meter. 90 The mass of Y glass microspheres is directly measured using a calibrated activity meter, and the activity meter measurement results are corrected using a calibration factor curve to achieve 90 Batch, fast and accurate measurement of the activity of Y glass microsphere products.

[0023] The beneficial effects of the present invention are as follows: 90 Y glass microspheres are gently and non-destructively digested to create 90 Y solution and 90 Y glass microsphere activity transfer relationship, and finally complete 90 The activity meter is calibrated under the conditions of Y glass microsphere standard sample, and then the calibrated activity meter is used to achieve 90 The radioactivity of Y glass microspheres can be measured quickly and accurately in batches. It has high measurement efficiency, high accuracy, simple operation and low cost, and is suitable for actual production and clinical applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 for 90 Flow chart of Y glass microsphere radioactivity measurement;

[0025] Figure 2 For the test in Example 2 3 H quenching calibration curve;

[0026] Figure 3 For Example 2 90 Y~ 3 H counting efficiency. DETAILED DESCRIPTION

[0027] The present invention will be described in detail below with reference to the embodiments described in the accompanying drawings, wherein like numerals represent like features throughout the drawings. Although specific embodiments of the present invention are shown in the drawings, it should be understood that the present invention may be implemented in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided to enable a more thorough understanding of the present invention and to fully convey the scope of the present invention to those skilled in the art.

[0028] It should be noted that certain words are used in the specification and claims to refer to specific components. Those skilled in the art should understand that technicians may use different nouns to refer to the same component. This specification and claims do not use the difference in nouns as a way to distinguish components, but use the difference in the functions of the components as the criterion for distinction. For example, "including" or "comprising" mentioned throughout the specification and claims are open-ended terms and should be interpreted as "including but not limited to". The subsequent description of the specification is a preferred embodiment of the present invention, but the description is based on the general principles of the specification and is not intended to limit the scope of the invention. The scope of protection of the present invention shall be as defined in the attached claims.

[0029] The present invention provides general and / or specific descriptions of the materials and test methods used in the experiments. In the following examples, unless otherwise specified, % represents wt%, i.e., weight percentage. All reagents or instruments used without indicating the manufacturer are commercially available conventional reagents, including: 89 Y glass sphere particle powder is provided by Xiantong Pharmaceutical Company. It is a glass sphere particle powder (solid) with a particle size of 10-45μm (>96%). It is made by smelting three oxides: yttrium oxide (Y2O3), silicon dioxide (SiO2), and aluminum oxide (Al2O3). The mass fractions of the three oxides are: Y2O3 40%±5.0%; SiO2 40%±6.0%; Al2O3 20%±5.0%, and the true density is 3.3±0.3g / cm 3 .

[0030] Example 1

[0031] Weigh 24.45 mg 89Y glass microspheres were placed in a crucible, and 176.57 mg of a flux (anhydrous sodium carbonate and boric acid, mass ratio 5:1) was added. After mixing, the mixture was melted at 900°C for 30 min to form a melt. The melt was cooled to room temperature and removed. 7.5 mL of 2.5 M nitric acid was added to the crucible. After complete dissolution and clarification, the solution was transferred to a 100 mL volumetric flask and diluted with water to 100 mL. 2.0 mL of the above solution was diluted to 10 mL with 0.1 M dilute nitric acid. Three replicates were prepared in parallel. The nuclide content of the solution was determined using inductively coupled plasma atomic emission spectrometry (ICP-OES). The results are shown in Table 1.

[0032] Table 1 89 Y glass microsphere digestion measurement results

[0033]

[0034] As can be seen from the measured data in Table 1, the deviation between the mass of each element in the solution after digestion and the original content of the glass microspheres is -0.5%, which proves that the yttrium glass microsphere digestion process developed in this patent achieves complete digestion of the microspheres without causing any loss of elements.

[0035] In addition, after many experiments, it was found that the flux and 90 When the mass ratio of Y glass microspheres is 3:1 to 100:1, the temperature is 800℃ to 1500℃, and the melting time is 20min to 120min, 90 Y glass microspheres can be completely melted to form a melt.

[0036] Example 2

[0037] 101.36mg yttrium[ 89 The glass microspheres were encapsulated in quartz bottles and sealed in irradiation aluminum cylinders before entering the CMRR reactor for irradiation. The reactor was started at 19:27 on July 24, 2020, and shut down at 07:19 on August 4, 2020, for a total of 248 hours and 22 minutes of irradiation, with an average thermal neutron flux rate of 2×10 13 cm -2 s -1 .

[0038] Cooled to August 21, 2020, weighed 3.15 mg 90Y glass microspheres were placed in a crucible, and 176.59 mg of a flux (anhydrous sodium carbonate and boric acid, mass ratio 5:1) was added. After mixing, the mixture was melted at 900 ° C for 30 min. The melt was cooled to room temperature and taken out. 7.5 mL of 2.5 M nitric acid solution was added. After complete dissolution and clarification of the solution, it was transferred to a 100 mL volumetric flask, diluted with water and fixed to 100 mL. Three portions of the dilution were taken in parallel, each 1 mL, and placed in a 20 mL glass liquid scintillation bottle. 15 mL of liquid scintillation liquid and 0.2 mL of stabilizer were added and mixed. The liquid scintillation CIEMAT / NIST method was used for measurement based on a commercial double-tube liquid scintillation analyzer. 90 Y solution activity. After dilution with water, the nitric acid concentration of the solution should be ≤1M so that no precipitation will occur when measuring the activity using the liquid scintillation method. The determination method is as follows:

[0039] 1) Use of tritium ( 3 H) Quench the standard source to measure the standard 3 H quenching calibration curve, the results are as follows Figure 2 As shown;

[0040] 2) Calculation based on liquid scintillation free parameter model 90 Y counting efficiency and tracer nuclides 3 The direct relationship curve of H counting efficiency is as follows. Figure 3 As shown;

[0041] 3) Measure using a liquid scintillation analyzer 90 Y dilution count rate, according to Figure 2 and Figure 3 Calculated 90 The activity of Y dilution was measured. The results are shown in Table 2.

[0042] Table 2 Liquid scintillation method determination 90 Y solution activity result 1

[0043]

[0044] 4) Calculate the end of irradiation (EOB) time based on the activity of 1 mL of dilution obtained by liquid scintillation measurement and the dilution multiple 90 The total activity of Y glass microspheres is 100.938 mCi and the specific activity is 0.9958 mCi / mg.

[0045] On August 24, 2020, 10.65 mg, 16.41 mg, 22.74 mg, 27.71 mg, 32.86 mg, 37.95 mg, 43.05 mg, and 50.05 mg of the above were weighed in sequence using a balance. 90Y glass microspheres were placed in 2 mL round-bottom vials, and a commercial activity meter manufactured by CAPINTEC, USA, was used. The position of the sample vial in the activity well was fixed during measurement, and the mass of the microspheres and the activity measurement value at the time of measurement were recorded. The liquid scintillation CIEMAT / NIST method was used to obtain the 90 The mass specific activity of Y glass microspheres is calculated to be 10.65mg, 16.41mg, 22.74mg, 27.71mg, 32.86mg, 37.95mg, 43.05mg, 50.05mg above 90 The actual activity of Y glass microspheres was calculated to obtain the calibration factor curve for direct measurement of microspheres using a commercial activity meter under these conditions, thus completing the calibration of the commercial activity meter. The results are shown in Table 3.

[0046] Table 3 Activity meter calibration factor curve

[0047]

[0048] The test items can be weighed during subsequent testing or production 90 The mass of Y glass microspheres is directly measured using a calibrated activity meter 90 The radioactivity of Y glass microspheres can achieve the purpose of obtaining product activity in batches, quickly and accurately, and applying pesticides precisely.

[0049] From the results in Table 3, it can be seen that if it does not dissolve, the commercial activity meter can be used to measure the 90 The activity measurement of Y glass microspheres will produce a large deviation, with the measured activity deviating from the true activity by nearly 60%, making it impossible to achieve accurate dosage of the drug, which proves the beneficial effects of the present invention.

[0050] Example 3

[0051] 101.22mg yttrium[ 89 The glass microspheres were encapsulated in quartz bottles and sealed in aluminum irradiation boxes before entering the CMRR reactor for irradiation. The reactor was started at 19:22 on July 8, 2022, and shut down at 12:00 on July 21.

[0052] On July 25, 2022, 10.8 mg of yttrium was weighed. 90 Place glass microspheres in a crucible and add 175.74 mg of a flux (anhydrous sodium carbonate and boric acid, mass ratio 5:1). Mix thoroughly and heat at 900°C for 30 minutes. Cool to room temperature and remove from the crucible. Add 7.5 mL of 2.5 M nitric acid. Once completely dissolved and the solution clarified, transfer to a 100 mL volumetric flask, dilute with water, and bring the volume to 100 mL. This is the mother solution. Add 1 mL of the mother solution to a 10 mL volumetric flask and dilute with water to 10 mL. This is the secondary dilution solution.

[0053] Three aliquots of the secondary dilution solution (20 μL each) were taken in parallel and added to a liquid scintillation vial containing 15 mL of liquid scintillation fluid, 0.2 mL of stabilizer, and 0.98 mL of ultrapure water. After mixing, the activity was measured using the liquid scintillation CIEMAT / NIST method on a commercial double-tube liquid scintillation analyzer. The measurement results are shown in Table 4.

[0054] Table 4 Liquid scintillation method determination 90 Y solution activity result 2

[0055]

[0056] 4) Based on the specific activity of the secondary dilution obtained by liquid scintillation measurement and the dilution factor, the end of irradiation (EOB) time is calculated. 90 The total activity of Y glass microspheres is 105.671 mCi and the specific activity is 1.04355 mCi / mg.

[0057] use 60 Co standard solution (PTB 2019-1193), prepare 1 tablet each 60 Co thin film source, 1 piece 60 Co and 90 Y mixed source, add 20μL to both sources to be tested 60 Co standard solution, after natural evaporation, continue to add 15μL (14.7mg) 90 The secondary dilution of Y microsphere digestion. The absolute activity was tested using the 4πβ(PC)-γ coincidence activity standard device, and the efficiency tracer method was used to measure the 60 Co source and 60 Co+ 90 The absolute activity of the Y mixed source is the activity of the mixed source minus the added 60 Co activity, obtained 90 The measurement results of Y source activity are shown in Table 5.

[0058] Table 5 4πβ-γ coincidence method determination 90 Activity of Y solution

[0059]

[0060] The EOB moment is calculated based on the specific activity of the secondary dilution solution measured by the 4πβ-γ coincidence method and the dilution multiple. 90 The total activity of Y glass microspheres is 104.217 mCi and the specific activity is 1.0296 mCi / mg.

[0061] From the measurement results of the liquid scintillation CIEMAT / NIST method and the 4πβ-γ coincidence method, it can be seen that the EOB moment can be measured by the two methods. 90The total activity deviation of Y glass microspheres is about 1.396%, which proves that a determination method developed by this patent 90 Y Accuracy of the glass microsphere activity method.

[0062] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any other manner. Any person skilled in the art may utilize the above-disclosed technical content to modify or modify the present invention into equivalent embodiments. However, any simple modifications, equivalent variations, and modifications to the above embodiments that do not depart from the technical content of the present invention and are based on the technical essence of the present invention remain within the scope of protection of the present invention.

Claims

1. A determination 90 The method for measuring the radioactivity of Y glass microspheres is characterized in that: The method comprises the following steps: (1) 90 The Y glass microspheres are mixed and melted with a flux to form a melt; (2) After the melt is cooled to room temperature, an acidic solution is added to dissolve the melt to form a solution; (3) Add water to dilute the solution and make it constant. Take a sample and use the absolute activity measurement method to determine the content of the solution. 90 Activity of Y; (4) Establish solution 90 Y activity and 90 The transfer relationship of Y glass microsphere activity is calculated to obtain a series of different mass M i of 90 Y The true activity of glass microspheres, where i = 1, 2, 3, ... N; (5) The different masses M in step (4) i of 90 Place Y glass microspheres into the activity meter, compare the actual activity with the measured value of the activity meter, determine the calibration factor curve of the activity meter, and calibrate the activity meter; (6) Weigh the test piece 90 The mass of Y glass microspheres was measured using a calibrated activity meter. 90 Radioactivity of Y glass microspheres.

2. The method according to claim 1, characterized in that In step (1), the flux and 90 The mass ratio of Y glass microspheres is 3:1 to 100:

1.

3. The method according to claim 1, characterized in that The flux in step (1) is anhydrous sodium carbonate and boric acid, and the mass ratio of the anhydrous sodium carbonate to boric acid is 1:1 to 10:1; the melting temperature is 800° C. to 1500° C., and the melting time is 20 min to 120 min.

4. The method according to claim 1, wherein The acidic solution in step (2) is a nitric acid solution having a concentration of 0.5M to 3M; and the mass volume ratio of the melt to the nitric acid solution is ≤50g / L.

5. The method according to claim 1, wherein After the dissolving solution in step (3) is diluted with water, the nitric acid concentration of the solution is ≤1M.

6. The method according to claim 1, characterized in that Determination in step (3) 90 The method for measuring the activity of Y solution is the liquid scintillation CIEMAT / NIST method or the 4πβ-γ coincidence measurement method.

7. The method according to claim 1, characterized in that In the solution described in step (4) 90 Y activity and 90 The transfer relationship of Y glass microsphere activity is: 90 Mass specific activity of Y glass microspheres.

8. The method according to claim 1, characterized in that The activity meter in step (5) is a well-type ionization chamber.

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