Method for rapidly measuring content of metal impurities in Ac-225 nuclide product liquid

Abstract

The invention discloses a method for rapidly measuring the content of metal impurities in an Ac-225 nuclide product liquid, which comprises the following steps: sampling the Ac-225 nuclide product liquid to be measured, and fixing the volume to obtain a sample to be measured; when the activity of the Ac-225 in the to-be-tested sample is equal to the activity of the Fr-221, measuring the radioactive activity of the Fr-221 by adopting a high-purity germanium gamma energy disperse spectroscopy so as to calculate the activity of the Ac-225 nuclide; respectively drawing standard curves of different metal impurity ions by adopting an inductively coupled plasma spectrometry; determining content signals of various metal impurity ions in the to-be-tested sample by adopting an inductively coupled plasma spectrometry, and obtaining the concentration of each impurity in the to-be-tested sample according to the standard curve; and calculating the content of the metal impurities in the Ac-225 nuclide product according to the concentration of each impurity in the to-be-tested sample, the constant volume and the activity of the Ac-225 nuclide. The method has the advantages of small loss of an Ac-225 nuclide product, high sensitivity, high accuracy and simplicity and convenience in operation, and has good practical value and popularization and application prospects.

Description

Technical Field

[0001] The invention belongs to the technical fields of analysis and testing, radioactivity measurement and nuclear medicine, and in particular relates to a method for rapidly measuring the content of metal impurities in Ac-225 nuclide product liquid. Background Art

[0002] The statements herein merely provide background information related to the present invention and do not necessarily constitute prior art.

[0003] Radioactive medical isotope drugs are a special type of drugs containing radioactive isotopes for medical diagnosis and treatment. They can achieve early screening, diagnosis, precision treatment and pain relief for malignant tumors, and are an important means to improve people's health level. α-targeted therapy has two obvious advantages over conventional therapy. Alpha radiation has a short range in human tissue (<0.1mm) and can selectively kill targeted cancer cells without affecting surrounding healthy tissues. Several MeV high-energy α radiation has a very high linear energy density and achieves efficient cell killing by acting on DNA double-strand and DNA cluster breaks. This damage is independent of the cell cycle and has nothing to do with its oxygenation state.

[0004] Ac-225 is a 100% alpha decay radionuclide with a half-life of t 1 / 2 The biological activity of Bi-209 is 9.96 days. It undergoes 4 alpha decays and 2 beta decays in the process of decaying to the stable nuclide Bi-209 (approximately stable), releasing alpha particles with a total energy of 27.5 MeV. It is considered to be the most suitable alpha targeted therapeutic nuclide for tumor treatment, especially for the treatment of tumors that have failed to be treated by other methods, especially in the advanced stage with multiple metastatic tumors.

[0005] For the production of Ac-225 by proton irradiation of thorium metal target (Th-232), the Ac-225 nuclide product obtained by separation and purification of the target solution may contain metal impurities such as strontium, barium, lead, lanthanum, cerium, etc. According to the "Drug Administration Law of the People's Republic of China" and the "Radioactive Drug Administration Measures", Ac-225 nuclide products are medical isotope drugs. Accurate and rapid detection of metal impurity content and quality control are of great significance in terms of drug safety and effectiveness.

[0006] At present, there is no report on the method for quickly measuring the content of metal impurities in Ac-225 nuclide products. It is imperative to establish a method for quickly measuring the content of metal impurities in Ac-225 nuclide products. Summary of the invention

[0007] In view of the shortcomings of the prior art, the present invention combines a high-purity germanium gamma spectrometer with an inductively coupled plasma atomic emission spectrometer to establish a method for rapidly measuring the metal impurity content in Ac-225 nuclide product liquid.

[0008] In order to achieve the above object, the present invention is implemented through the following technical solutions:

[0009] A method for rapidly measuring the content of metal impurities in Ac-225 nuclide product liquid comprises the following steps:

[0010] Take a sample of the Ac-225 nuclide product liquid to be tested, and adjust the volume to obtain the sample to be tested;

[0011] When the activity of Ac-225 in the sample to be tested is equal to that of Fr-221, the activity of Ac-225 nuclide is calculated by measuring the radioactivity of Fr-221 using a high purity germanium gamma spectrometer;

[0012] Inductively coupled plasma spectrometry was used to draw standard curves for different metal impurity ions;

[0013] The inductively coupled plasma spectrometry is used to determine the content signals of various metal impurity ions in the test sample, and the concentration of each impurity in the test sample is obtained according to the standard curve;

[0014] The content of metal impurities in the Ac-225 nuclide product is calculated based on the concentration of each impurity in the test sample, the fixed volume and the activity of the Ac-225 nuclide.

[0015] Ac225 is a radioactive nuclide, and the impurity element content contained in it needs to be measured by activity concentration. Therefore, the activity of the sample needs to be measured before using inductively coupled plasma measurement. Traditional activity detection instruments are generally activity meters, but the inventors have repeatedly found that using a high-purity germanium gamma spectrometer to measure the activity of Ac225 has higher sensitivity and accuracy. Therefore, the present invention uses a high-purity germanium gamma spectrometer to measure the activity of Ac225.

[0016] Ac-225 decays into Fr-221 through α decay. The half-life of Fr-221 is 4.9 minutes, and it emits γ rays with an energy of 218 KeV during decay. The activity of Fr-221 in the sample to be tested depends on the decay of Ac-225. After a period of time 10 times longer than the half-life of Fr-221, Ac-225 and Fr-221 reach radioactive equilibrium, at which time the activity of Ac-225 is equal to that of Fr-221. A high-purity germanium γ spectrometer is used to measure the γ rays emitted by Fr-221 to calculate the activity of the nuclide Ac-225.

[0017] In some embodiments, the test sample is left to stand for a period of time that is 10 times longer than the half-life of Fr-221, and Ac-225 and Fr-221 reach radioactive equilibrium, at which time the activity of Ac-225 is equal to the activity of Fr-221.

[0018] In some embodiments, the solvent of the Ac-225 nuclide product solution to be tested is a dilute nitric acid solution.

[0019] Preferably, the volume percentage of nitric acid in the dilute nitric acid solution is 1-3%, preferably 2%.

[0020] In some embodiments, the measurement mode when using a high-purity germanium gamma spectrometer for measurement is an integration mode, the measured nuclide is Fr-221, and the measurement time is 900 to 1500 seconds, preferably 1200 seconds.

[0021] In some embodiments, the metal impurities are one or more of strontium, lead, lanthanum, cerium or barium.

[0022] Preferably, the measured spectrum line of barium is 233.527 spectrum line; the measured spectrum line of lead is 220.353 spectrum line; the measured spectrum line of lanthanum is 379.478 spectrum line; the measured spectrum line of cerium is 413.765 spectrum line; and the measured spectrum line of strontium is 460.733 spectrum line.

[0023] In some embodiments, the operating parameters of the inductively coupled plasma spectrum are: cooling gas is 14-16 lPM, auxiliary gas is 0.2-1.0 lPM, nebulizing gas is 28-32 PSI (concentric nebulizer); peristaltic pump speed is 25-28 RPM; radio frequency power is 1.0-1.2 KW; sample lifting time is 30 s; and the number of integration times is 3 times.

[0024] In some embodiments, the formula for calculating the metal impurity content in the Ac-225 nuclide product is:

[0025]

[0026] Where, X: the content of metal impurities in the sample, μg / GBq;

[0027] C: The concentration of metal impurities in the Ac-225 nuclide product to be tested obtained from the standard curve, μg / ml;

[0028] V: volume of the sample to be tested, ml;

[0029] A: Activity of the Ac-225 nuclide product to be tested, Bq; 10 9 The beneficial effects achieved by one or more embodiments of the present invention are as follows:

[0030] 1. The loss of Ac-225 nuclide product liquid is small. The present invention combines a high-purity germanium gamma spectrometer with an inductively coupled plasma atomic emission spectrometer. After preparing the test sample, the high-purity germanium gamma spectrometer is used for non-destructive analysis to obtain the radioactivity of the Ac-225 nuclide product liquid test sample, and then the inductively coupled plasma spectrometer is used for analysis to obtain the metal impurity ion content. This method does not require multiple sampling, reduces the loss of Ac-225 nuclide product liquid, and also reduces the radiation exposure of the test personnel.

[0031] 2. High sensitivity and high precision. The present invention adopts the standard curve method to simultaneously determine the contents of five mixed elements using an inductively coupled plasma atomic emission spectrometer. The spectral lines of the selected five elements do not interfere with each other, have good stability, and have a high signal-to-background ratio, which can achieve high sensitivity and high precision detection of these impurity elements and improve the accuracy of the analysis results.

[0032] 3. Simple and convenient operation. The operation steps of this method are simple and clear, easy to master, and the analysis and detection cycle is short, which greatly improves the detection efficiency. It can be widely promoted and applied to the determination of impurity metal element content in radioactive drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0034] Figure 1 This is the gamma energy spectrum of the Ac-225 product to be tested in Example 1. DETAILED DESCRIPTION

[0035] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0036] The present invention will be further described below in conjunction with the embodiments.

[0037] Main instruments and reagents

[0038] Inductively coupled plasma spectrometer (Prodigy7, Teledyne leeman labs), reverse osmosis deionized water purer (lD-DI-II-20, Liding), high purity germanium gamma spectrometer (ORTEC GEM-C30, AMETEK);

[0039] Concentrated nitric acid (super pure grade, Sinopharm Chemical Reagent Co., Ltd.), ultrapure water (resistivity ≥ 18.2MΩ·cm), strontium single element standard substance (1000μg / ml, GSB 04-1754-2004), barium single element standard substance (1000ug / ml, GSB04-1717-2004), lead single element standard substance (1000μg / ml, GSB04-1742-2004), lanthanum single element standard substance (1000μg / ml, GSB 04-1774-2004), cerium single element standard substance (1000μg / ml, GSB04-1775-2004). The above single element standard solutions are all from the National Nonferrous Metals and Electronic Materials Analysis and Testing Center. Each level of standard solution is diluted with a 2% by volume dilute nitric acid solution.

[0040] Preparation of test samples

[0041] A 120MeV high-energy proton accelerator was used to irradiate a 60g metal thorium target, with a current of 100μA, irradiation for 10 days, and cooling for 3 days. The irradiated thorium target was cut into small pieces, nitric acid and a catalyst were added to dissolve it, and a four-stage series separation and purification process of a cation exchange resin column, a UTEVA or TK200 resin extraction column, a DGA resin extraction column, and an 1N resin extraction column was used to obtain the Ac-225 nuclide product liquid.

[0042] After separation and purification, the Ac-225 nuclide product solution was obtained. 2 μl was taken into a 5 ml centrifuge tube, and 1.98 ml of solvent was added to the centrifuge tube to make the volume 2 ml as the test sample. The solvent of the test sample was 2% by volume nitric acid.

[0043] Radioactivity measurement

[0044] The Ac-225 sample to be tested was placed for 49 minutes, at which time the parent nuclide Ac-225 and the daughter nuclide Fr-221 reached radioactive equilibrium. The radioactivity of the sample was measured using a high-purity germanium gamma spectrometer, with Fr-221 selected as the analytical nuclide and the analysis time set to 1200 seconds. After the measurement process was completed, the readings recorded included: measurement time, date, activity reading, unit, and sample identification, etc.

[0045] Metal impurity ion measurement

[0046] The content of metal impurity ions in the above samples was measured by inductively coupled plasma spectroscopy.

[0047] Turn on the instrument and establish the test method:

[0048] The instrument conditions are: cooling gas is 16lPM, auxiliary gas is 0.3lPM, atomizing gas is 30PSI (concentric atomizer); peristaltic pump speed is 25RPM; radio frequency power is 1.0KW. After the instrument is successfully ignited and stable, the sample measurement method is established. The content of impurities strontium, lead, lanthanum, cerium, and barium in Ac-225 nuclide products is low. The spectral lines with few interfering elements and high signal-to-background ratio are selected, which are: barium, 233.527 spectrum; lead, 220.353 spectrum; lanthanum: 379.478 spectrum; cerium: 413.765 spectrum; strontium: 460.733 spectrum.

[0049] Prepare mixed element standard solution and establish standard curve

[0050] Take single element standard substances of strontium, barium, lead, lanthanum and cerium (1000 μg / ml, matrix is ​​1.0 mol / l nitric acid) and prepare the following mixed standard solutions respectively:

[0051] Mixed standard solution 1, the concentrations of strontium, lead, lanthanum, cerium and barium are 0.01μg / ml, 0.05μg / ml, 0.01μg / ml, 0.05μg / ml and 0.01μg / ml respectively;

[0052] Mixed standard solution 2, the concentrations of strontium, lead, lanthanum, cerium and barium are 0.05μg / ml, 0.10μg / ml, 0.05μg / ml, 0.10μg / ml and 0.05μg / ml respectively;

[0053] Mixed standard solution 3, the concentrations of strontium, lead, lanthanum, cerium and barium are 0.10μg / ml, 0.20μg / ml, 0.10μg / ml, 0.20μg / ml and 0.10μg / ml respectively;

[0054] In the mixed standard solution 4, the concentrations of strontium, lead, lanthanum, cerium and barium are 0.20 μg / ml, 0.30 μg / ml, 0.20 μg / ml, 0.30 μg / ml and 0.20 μg / ml respectively.

[0055] A series of standards were established with a blank solution of 2% HNO3 as STD 0 and mixed standard solutions 1, 2, 3, and 4 as STD 1, STD 2, STD3, and STD 4, respectively. A standard curve was plotted with the response value of the element to be measured as the ordinate and the correction concentration as the abscissa. The correlation coefficients of the standard curves of the five elements were all greater than 0.99.

[0056] Standard curve, detection limit, quantitation limit

[0057] 2% nitric acid solution was used as a blank sample, and the measurement was repeated 20 times to calculate the standard deviation of the intensity values ​​of the spectral lines of each element. The concentration corresponding to 3 times the standard deviation was the detection limit of the method, and the concentration corresponding to 10 times the standard deviation was the quantitative limit of the method. The results are shown in Table 1.

[0058] Table 1 Detection limit and quantification limit of the detection method

[0059]

[0060] Spike recovery and precision experiments

[0061] According to the established analytical method, the metal ion content in the mixed standard solution 3 was tested and recorded as the background value. A certain volume of the mixed standard solution was added to this standard solution to prepare the spiked sample, and the measurement was repeated 6 times. The spiked recovery and RSD of each element were calculated, as shown in Table 2. The average spiked recovery of the five elements was between 96.0% and 104.0%, indicating a high accuracy; the average relative standard deviation was between 0.01% and 0.237%, indicating good precision.

[0062] Table 2 The recovery and precision results of the spiked method of this embodiment

[0063]

[0064]

[0065] Metal impurity analysis test and results of the test samples

[0066] Using the above method, the Ac-225 sample to be tested was first tested by a high-purity germanium gamma spectrometer, and the measured gamma spectrum was as follows: Figure 1 As shown in Figure 1, the activity of Fr-221 is 7.075E+04Bq, that is, the activity of Ac-225 is 7.075E+04Bq.

[0067] Then, the impurity metal ion content of the test sample was analyzed by inductively coupled plasma spectrometer, and the results are shown in Table 3 below.

[0068] Table 3 Impurity content test results of Ac-225 test sample in this example

[0069]

[0070]

[0071] The content of metal impurities strontium, lead, lanthanum, cerium and barium in Ac-225 nuclide product liquid is calculated according to the following formula:

[0072]

[0073] In the formula,

[0074] X: the content of metal impurities strontium, lead, lanthanum, cerium and barium in the sample, μg / GBq;

[0075] C: The content of strontium, lead, lanthanum, cerium and barium in the Ac-225 nuclide product solution to be tested obtained from the standard curve, μg / ml;

[0076] V: volume of the sample to be tested, ml;

[0077] A: Activity of the Ac-225 nuclide product solution to be tested, Bq; 10 9 The conversion multiple.

[0078] The final metal content in the Ac-225 nuclide product solution was calculated and the results are shown in Table 4 below.

[0079] Table 4 Final calculation results of metal impurity content of Ac-225 nuclide product liquid

[0080]

[0081] In summary, since the content of metal impurities in the test samples of Ac-225 nuclide products is small and the concentration range is within the standard curve, the prepared test samples can be directly used for inductively coupled plasma spectrometer analysis after non-destructive analysis by high-purity germanium γ-ray spectrometer. The content of each metal impurity in the test sample obtained is divided by the radioactivity of the test sample to obtain the content of metal impurities in the Ac-225 nuclide product liquid. The rapid analysis of the content of metal impurities in the Ac-225 nuclide product liquid is achieved, the measurement speed is improved, the loss of nuclide products caused by multiple sampling is avoided, and the radiation exposure of test personnel is also reduced.

[0082] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for rapidly measuring the content of metal impurities in Ac-225 nuclide product liquid, characterized in that: The steps include: Take a sample of the Ac-225 nuclide product liquid to be tested, and adjust the volume to obtain the sample to be tested; When the activity of Ac-225 in the sample to be tested is equal to that of Fr-221, the activity of Ac-225 nuclide is calculated by measuring the radioactivity of Fr-221 using a high purity germanium gamma spectrometer; Inductively coupled plasma spectrometry was used to draw standard curves for different metal impurity ions; The inductively coupled plasma spectrometry is used to determine the content signals of various metal impurity ions in the test sample, and the concentration of each impurity in the test sample is obtained according to the standard curve; The content of metal impurities in the Ac-225 nuclide product is calculated based on the concentration of each impurity in the test sample, the fixed volume and the activity of the Ac-225 nuclide.

2. The method for rapidly measuring the content of metal impurities in Ac-225 nuclide product liquid according to claim 1, characterized in that: The test sample is left to stand for a period of time that is 10 times longer than the half-life of Fr-221. Ac-225 and Fr-221 reach radioactive equilibrium, at which point the activity of Ac-225 is equal to that of Fr-221.

3. The method for rapidly measuring the content of metal impurities in Ac-225 nuclide product liquid according to claim 1, characterized in that: The solvent of the Ac-225 nuclide product solution to be tested is a dilute nitric acid solution.

4. The method for rapidly measuring the content of metal impurities in Ac-225 nuclide product liquid according to claim 3, characterized in that: The volume percentage of nitric acid in the dilute nitric acid solution is 1-3%.

5. The method for rapidly measuring the content of metal impurities in Ac-225 nuclide product liquid according to claim 4, characterized in that: The volume percentage of nitric acid in the dilute nitric acid solution is 2%.

6. The method for rapidly measuring the content of metal impurities in Ac-225 nuclide product liquid according to claim 1, characterized in that: The measurement mode when using a high-purity germanium gamma spectrometer for measurement is the integration mode, the measurement nuclide is Fr-221, and the measurement time is 900 to 1500 seconds, preferably 1200 seconds.

7. The method for rapidly measuring the content of metal impurities in Ac-225 nuclide product liquid according to claim 1, characterized in that: The metal impurities are one or more of strontium, lead, lanthanum, cerium or barium.

8. The method for rapidly measuring the content of metal impurities in Ac-225 nuclide product liquid according to claim 1, characterized in that: The measured spectrum line of barium is 233.527; the measured spectrum line of lead is 220.353; the measured spectrum line of lanthanum is 379.478; the measured spectrum line of cerium is 413.765; and the measured spectrum line of strontium is 460.

733.

9. The method for rapidly measuring the content of metal impurities in Ac-225 nuclide product liquid according to claim 1, characterized in that: The working parameters of the inductively coupled plasma spectrum are: cooling gas is 14-16 lPM, auxiliary gas is 0.2-1.0 lPM, atomizing gas is 28-32 PSI; peristaltic pump speed is 25-28 RPM; radio frequency power is 1.0-1.2 KW; sample lifting time is 30 s; and the number of integrations is 3 times.

10. The method for rapidly measuring the content of metal impurities in Ac-225 nuclide product liquid according to claim 1, characterized in that: The calculation formula for the metal impurity content in Ac-225 nuclide product liquid is: Where, X: the content of metal impurities in the sample, μg / GBq; C: The content of metal impurities in the Ac-225 nuclide product to be tested obtained from the standard curve, μg / ml; V: volume of the sample to be tested, ml; A: Activity of the Ac-225 nuclide product to be tested, Bq; 10 9 The conversion multiple.

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