Methods for controlling the activity ratio of terbium-160 to terbium-161 in the preparation of terbium-161

Abstract

This invention relates to a method for controlling the activity ratio of terbium-160 to terbium-161 in the preparation of terbium-161, comprising: S1, placing a natural Gd target or a high-abundance 160Gd or 158Gd target in a reactor for irradiation, then removing and cooling the target, dissolving the Gd target, analyzing the radioactivity of 161Tb ATb-161 and 159Gd AGd-159 in the solution, and calculating the nuclear reaction rates Øthermal σGd-160 and Øthermal σGd-158; S2: Place the natural Tb target in the reactor for irradiation, then remove and cool it. Dissolve the natural Tb target and analyze the radioactivity of 160Tb in the solution (ATb-160). Calculate the nuclear reaction rate Øthermal σTb-159. S3: Based on the nuclear reaction rate data obtained in S1 and S2, calculate the relationship between the irradiation time of a high-abundance 160Gd (greater than 90%) target (containing 158Gd and 159Tb impurities) and the 160Tb / 161Tb activity ratio generated.

Description

Technical Field

[0001] This invention belongs to the field of nuclear chemistry, specifically a method for controlling the activity ratio of terbium-160 to terbium-161 in the preparation of terbium-161. Background Technology

[0002] Targeted radionuclide therapy is an important method for treating cancer. Lutetium-177 ( 177 Lu (Radioactive Oxygenase) has been widely used in clinical targeted radionuclide therapy. (And...) 177 Compared to Lu, Terbium-161 ( 161 Tb has similar nuclear properties, and both have similar half-lives. T 1 / 2 （Tb-161） =6.89 d vs. T 1 / 2 （Lu-177） =6.65 d) and emits similar β rays ( 161 Tb: E β （Tb-161） =157keV vs. 177 Lu: E β （Lu-177） =149 keV). The different characteristics are, (1) 161 Tb emits gamma rays at lower energies ( 161 Tb: 74.6 keV / 10.2%; 48.9 keV / 17.0% vs. 177 Lu: 208.4 keV / 10.4%; 112.9 keV / 6.2%), which can be applied to SPECT scanning imaging and evaluation of radiotherapy effects; (2) 161 Tb emits more Auger electrons and internal conversion electrons. 161 On average, each decay of Tb releases 12 electrons, while 177 On average, Lu releases one electron per decay. 161 Tb can provide a higher local dose density, resulting in better treatment effects and precise removal of tiny lesions. 161 Tb not only emits beta and gamma rays of suitable energy, but also possesses the ability to emit high-energy Auger electrons and internal conversion electrons. Therefore, 161 Tb has become a new type of medical isotope, attracting much attention internationally.

[0003] To realize the application of the novel medical isotope terbium-161 drug, the primary condition is to prepare medical-grade terbium-161. 161 Tb originates from 160 Gd thermal neutron capture (activation) reaction, 160 Gd (n, γ)161 Gd 161 Tb By targeting high-abundance oxide Gd into the reactor for irradiation, in addition to producing... 161 In addition to Tb, stable Gd and stable dysprosium-161 are also produced. 161 Tb decay products) 160 Tb ( 158 Gd two-stage activation products and impurities 159 Major impurities include Tb primary activation products. 161 For Dy and Gd, they can be removed through chemical separation. 160 Tb(T) 1 / 2 =72.3 d) is 161 Isotopes of Tb are difficult to remove through chemical separation methods. 160 Tb has a half-life much longer than 161 Tb cannot be removed by cooling. Because... 160 Tb has a long half-life and produces high-energy gamma rays; its activity directly affects the quality of drugs. 160 Tb / 161 Tb activity ratio becomes 161 Tb is a core indicator for products. Therefore, controlling the activity ratio of terbium-160 to terbium-161 in terbium-161 is crucial.

[0004] Internationally adopted 160 Gd preparation 161 Reports indicate that 5–40 mg of Tb was used in the FRM-II (Germany), BER II (Germany), and RHF ILL (France) reactors. 160 Gd(NO3)3 target ( 160 Gd abundance 98.2%. Targets were used in FRM-II and BER-II reactors (neutron flux approximately 10⁻⁶). 14 n·cm 2 ·s 1 Irradiated for 14 days, then cooled for 1–3 days. 161 The specific activity of Tb is approximately 2.8 TBq / mg; in the RHF ILL reactor (neutron flux of 8 × 10⁻⁶), the specific activity is approximately 2.8 TBq / mg. 14 n·cm 2 ·s 1 Irradiated for 7 days, then cooled for 24 days. 161The Tb specific activity decreased to 2.1 TBq / mg. Aziz et al. in Indonesia irradiated approximately 100 mg of natural gadolinium target (Gd₂O₃) in the GA Siwabessy Multi-purpose reactor, achieving a thermal neutron flux of approximately 10⁻⁶ TBq / mg. 14 n·cm 2 ·s 1 Irradiation for 4 days, 161 The activity of Tb can reach 105.93 mCi. The China Academy of Engineering Physics irradiated 240 mg of Tb in the Mianyang research reactor. 160 Gd₂O₃ target material, irradiated for 7 days, yielded 33.4 GBq. 161 Tb.

[0005] The above work did not specifically describe the method for controlling the activity of terbium-160 during the preparation of terbium-161. Summary of the Invention

[0006] In view of this, the present invention is based on 160 Starting with the source of Tb's generation, the problem was solved. 160 Tb / 161 Tb activity ratio and 161 The problem of unbalanced Tb production.

[0007] To achieve the above objectives, the present invention provides a method for controlling the activity ratio of terbium-160 to terbium-161 in the preparation of terbium-161, comprising: S1, targeting natural Gd or high abundance 160 Gd, 158 The Gd target was placed in the reactor for irradiation, then removed and cooled. The natural Gd target was dissolved, and the solution was analyzed. 161 The radioactivity of Tb A Tb-161 and 159 The radioactivity of Gd, A Gd-159 Calculate the nuclear reaction rate Ø 热 σ Gd-160 and Ø 热 σ Gd-158 ; S2, the natural Tb target was placed in the reactor for irradiation, then removed and cooled to dissolve the natural Tb target. The dissolved solution was then analyzed. 160 The radioactivity of Tb A Tb-160 Calculate the nuclear reaction rate Ø 热 σ Tb-159 ; S3, based on the nuclear reaction rate data obtained from S1 and S2, calculates the high abundance 160 Gd target irradiation time and generation 160 Tb / 161 The relationship between Tb activity ratio.

[0008] Among them, natural Gd targets or high abundance 160 Gd, 158 There are no particular limitations on the irradiation time of Gd targets and natural Tb targets placed in the reactor and the subsequent cooling time. For example, irradiation can be carried out for 1 to 3 hours, such as 1 hour, 1.5 hours, 2 hours, 2.5 hours or 3 hours; and cooling can be carried out for 24 to 72 hours, such as 24 hours, 36 hours, 48 ​​hours or 72 hours.

[0009] In some implementations, in S1, calculations are performed using Equations 1 and 2 respectively to obtain... 160 Gd (n, γ) 161 Gd nuclear reaction rate Ø 热 σ Gd-160 (ns) -1 )and 158 Gd (n, γ) 159 Gd nuclear reaction rate Ø 热 σ Gd-158 (ns) -1 ): (Equation 1) (Equation 2); In Equations 1 and 2, Ø 热 The thermal neutron flux rate in the reactor, in n.cm -2 .s -1 ;σ Gd-160 nuclide 160 The thermal neutron reaction cross section of Gd, cm 2 ;σ Gd-158 nuclide 158 The thermal neutron reaction cross section of Gd, cm 2 N Gd-160 For irradiating Gd target 160 The number of Gd atoms; N Gd-158 For irradiating Gd target 158 The number of Gd atoms; λ Gd-159 nuclide 159 The decay constant of Gd, s -1 ;λ Tb-161 nuclide 161 The decay constant of Tb, s -1 ;λ Gd-161 nuclide 161 The decay constant of Gd, s -1 T is the Gd target irradiation time, in seconds; t is the time difference between the start and stop of the measurement, in seconds; A Tb-161 To generate products 161 The activity of Tb at the start of measurement, Bq; AGd-159 To generate products 159 The activity of Gd at the start of the measurement, Bq.

[0010] In some implementations, in S2, the result is obtained using Equation 3. 159 Tb (n, γ) 160 Tb nuclear reaction rate Ø 热 σ Tb-159 (ns) -1 ): (Equation 3); In Equation 3, Ø 热 The flux of thermal neutrons in the reactor, n.cm -2 .s -1 ;σ Tb-159 nuclide 159 The thermal neutron reaction cross section of Tb, cm 2 N Tb-159 For irradiation of Tb target 159 The number of atoms of Tb; λ Tb-160 nuclide 160 The decay constant of Tb, s -1 T represents the Tb target irradiation time, in seconds; t represents the time difference between the start and end of the measurement, in seconds; A Tb-160 To generate products 160 The activity of Tb at the start of the measurement, Bq.

[0011] In some implementations, in S3, the relationship is obtained by calculation using Equation 4, wherein, 160 Gd (n, γ) 161 Gd, 158 Gd (n, γ) 159 The nuclear reaction rate of Gd was obtained from S1. 热 σ Gd-160 Ø 热 σ Gd-158 (ns) -1 ); 159 Tb(n, γ) 160 The Tb nuclear reaction rate was obtained from data in S2. 热 σ Tb-159 (ns) -1 ): (Equation 4) in,

[0012]

[0013]

[0014]

[0015] .

[0016] In some embodiments, the method further includes: Based on S3 160 Gd target irradiation time and generation 160 Tb / 161 The relationship between Tb activity ratio and irradiation time was optimized and controlled to achieve irradiation. 160 Gd target generation 160 Tb and 161 Control of Tb activity ratio.

[0017] In some embodiments, the natural Gd target 158 Gd and 160 The abundances of Gd were 28.84% and 21.86%, respectively.

[0018] In some embodiments, the high abundance 160 Gd, 158 Gd target is 160 Gd abundance > 28.84%, 158 Targets with Gd abundance greater than 21.86%.

[0019] In some embodiments, the natural Tb target has 100% 159 Tb.

[0020] In some embodiments, the high-abundance Gd target has an abundance greater than 90%. 160 Gd.

[0021] In some implementations, controlling the 160 Tb / 161 Tb activity ratio less than 1×10 -4 .

[0022] Therefore, in the method of the present invention, the concentration of Gd and Tb in the reactor is accurately determined using natural Gd and Tb targets. 160 Gd (n, γ) 161 Gd nuclear reaction rate Ø 热 σ Gd-160 , 158 Gd (n, γ) 159 Gd nuclear reaction rate Ø 热 σ Gd-158 Instead of an isolated reaction cross section σ, the calculation introduces the product of Øσ, closely simulating the actual nuclear reaction process; by selecting high abundance... 160 Using Gd as a target material effectively improves 161 Tb production, significantly reduced generation160 Tb activity; using high purity 160 Gd (to reduce impurities in the target material, such as...) 159 Using Tb content as a target material, the generated [material] was significantly reduced. 160 The activity levels of Tb and the radioactivity levels of impurities after Gd target irradiation are beneficial for radiation protection; a reasonable irradiation time can curb radiation. 159 Gd production 160 Tb activity (second-order reaction). Attached Figure Description

[0023] Figure 1 The irradiation time and the resulting product are shown in step S3 of the method of the present invention. 160 Tb / 161 Graph showing the relationship between Tb activity ratio. Detailed Implementation

[0024] The following detailed description discusses exemplary embodiments. The specific embodiments included herein should not be construed as limiting the invention. Furthermore, while specific language may be used to describe features, actions, and / or structures in the embodiments described herein, the claims are not limited to the described features, actions, and / or structures. Those skilled in the art will understand that other embodiments, including improvements, are within the spirit and scope of the invention.

[0025] Throughout this specification, unless otherwise specified, the terminology used herein should be understood as having the meaning as commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0026] Terbium-161, with its superior nuclear properties including emission of low-energy gamma rays, a higher concentration of Auger electrons, and internal conversion electrons, has become a novel medical isotope attracting significant international attention. The primary condition for realizing the application of this novel medical isotope, terbium-161, is the production of medical-grade terbium-161. Because... 160 Tb has a long half-life and produces high-energy gamma rays; its activity directly affects the quality of drugs. 160 Tb / 161 Tb activity ratio becomes 161 The core metrics of Tb products.

[0027] generally, 161 The preparation of Tb is carried out by the following method: First, a Gd target is placed in a reactor and irradiated, and Tb is continuously generated through the nuclear reaction of reaction (I). 161 After irradiation, other impurities are separated to obtain Tb. 161 Tb.

[0028] 160Gd (n, γ) 161 Gd 161 Tb formula (I) While irradiating the Gd target, it is possible to generate 160 Tb has two main side reactions, and their reaction equations are as follows: 158 Gd (n, γ) 159 Gd 159 Tb(n, γ) 160 Tb formula (II) 159 Tb(n, γ) 160 Tb (III) 160 The presence of Tb will seriously affect the development of novel medical isotopes. 161 The quality of Tb drugs. And due to... 160 Tb and 161 The high degree of similarity in chemical properties between Tb and Tb makes it difficult to achieve satisfactory isotopic separation using conventional methods. Therefore, how to balance... 160 Tb and 161 Tb activity ratio and 161 Tb production is key to achieving this goal.

[0029] In order to solve 160 Tb and 161 Tb activity ratio and 161 The problem of unbalanced Tb production reduces high abundance. 161 The production cost of Tb, this invention provides a 161 Tb preparation 160 Tb and 161 Tb activity ratio control method. Therefore, this invention... 160 Starting with the source of Tb's generation, the problem was solved. 160 Tb / 161 Tb activity ratio and 161 The problem of unbalanced Tb production.

[0030] The control method of this application can effectively reduce the activity of terbium-160 in terbium-161 products. Specifically, the method includes... 160 Gd (n, γ) 161 Gd nuclear reaction rate Ø 热 σ Gd-160 , 158 Gd (n, γ) 159 Gd nuclear reaction rate Ø 热 σ Gd-158 , 159 Tb (n, γ)160 Tb nuclear reaction rate Ø 热 σ Tb-159 The determination of high abundance 160 Gd (greater than 90%) target (including 158 Gd, 159 Tb impurities) irradiation time and formation 160 Tb / 161 The process includes calculating the relationship between Tb activity ratio and other parameters. Based on the calculation results, high irradiation abundance is achieved by controlling the irradiation time. 160 Gd (greater than 90%) target generation 160 Tb activity was controlled by selecting high abundance levels. 160 Using Gd as a target material effectively improves 161 Tb production significantly reduced by the reaction (II) described above. 160 Tb activity; using high purity 160 Gd (to reduce impurities in the target material, such as...) 159 Using the content of Tb as a target material, the amount generated by the above reaction formula (III) is significantly reduced. 160 Tb activity and the level of radioactivity of impurities after Gd target irradiation.

[0031] This method allows operators to optimize irradiation time and effectively control irradiation. 161 Tb products 160 Tb activity, effectively reducing 161 Tb products 160 Tb / 161 The ratio of Tb is a medical isotope. 161 This provides important basic data for the subsequent separation, purification, and application of Tb.

[0032] The present invention will be described in more detail below through embodiments. It should be understood that the embodiments described below are exemplary and are only used to explain this application, and should not be construed as limiting this application. Where specific techniques or conditions are not specified in the embodiments, they shall be performed in accordance with the techniques or conditions described in the literature in the art or according to the product instructions. Reagents or instruments used, unless otherwise specified, are all conventional products that can be obtained commercially.

[0033] Example S1: 22 mg of natural Gd target was placed in the reactor and irradiated for 2.5 h. After cooling for 100 h, the natural Gd target was dissolved, and the dissolved solution was analyzed using an HPGe (γ) spectrometer. 161 Tb and 159 The radioactivity of Gd is respectively A Tb-161 A Gd-159 They are 1.6×10 4 Bq, 2.7×10 4Bq. Calculated according to Equations 1 and 2, we get... 160 Gd (n, γ) 161 Gd nuclear reaction rate Ø 热 σ Gd-160 and 158 Gd (n, γ) 159 Gd nuclear reaction rate Ø 热 σ Gd-158 They are 1.33×10 -13 ns -1 6.48×10 -13 ns -1 The values ​​for Equations 1 and 2 are as follows.

[0034] Formula 1:

[0035] λ Gd-161 =3.16×10 -3 s -1 , λ Tb-161 =1.15×10 -6 s -1 N Gd-160 =1.865×10 19 T = 8520 s, t = 360840 s Formula 2:

[0036] λ Gd-159 =1.04×10 -5 s -1 N Gd-158 =2.11×10 19 T = 8520 s, t = 360840 s S2, 10 mg of natural Tb target was placed in the reactor and irradiated for 2 h 22 min, then cooled for 50 h to dissolve the natural Tb target. The dissolved solution was analyzed using an HPGe (γ) spectrometer. 160 The radioactivity of Tb is A Tb-160 2.5×10 5 Bq. Calculated using equation (3), we obtain... 159 Tb (n, γ) 160 Tb nuclear reaction rate Ø 热 σ Tb-159 (ns) -1 The value is 7.01 × 10 -12 ns -1 .

[0037] Formula 3:

[0038] λ Tb-160 =1.11×10 -7s -1 N Tb-159 =3.79×10 19 T = 8520 s, t = 180000 s S3, high abundance is obtained by equation (4). 160 Gd target (including) 158 Gd, 159 Tb impurities) irradiation time and formation 160 Tb / 161 The relationship between Tb activity ratio and the results shown in Figure 1 middle.

[0039] The high abundance adopted 160 The chemical purity of Gd in Gd is greater than 99.9%, but it is calculated as 100%; 160 The abundance of Gd was 92.27%. The contents of Tb were 15 ppm and 45 ppm, with the abundance of 159Tb being 100%. Other parameters have been given or calculated previously.

[0040] High abundance derived from S3 160 Gd target irradiation time and generation 160 Tb / 161 The relationship between Tb activity ratio and irradiation time is used to achieve high irradiation abundance. 160 Gd (greater than 90%) target generation 160 Tb activity is effectively controlled. Specifically, 160 Tb / 161 Tb activity ratio less than 1×10 -4 The irradiation time was 96 hours.

[0041] In the present invention 161 Tb preparation 160 The Tb activity control method utilizes natural Gd and natural Tb targets to simulate real-world conditions. 160 The generation process of Tb allows for relatively simple determination of reasonable irradiation time and optimization. 160 Gd abundance and control 159 Tb content, to balance 160 Tb / 161 Tb activity ratio and 161 Tb yield, high accuracy of results, effectively achieving high abundance 161 Tb preparation 160 Control of Tb activity leads to high abundance 161 The cost of Tb preparation has been reduced, and the radiation protection requirements have also been lowered.

[0042] Although this disclosure has been described with reference to specific exemplary embodiments thereof, many different variations, modifications, etc. will become apparent to those skilled in the art.

[0043] By studying the accompanying drawings, the disclosure, and the appended claims, those skilled in the art can understand and implement variations of the disclosed embodiments in the practice of this disclosure.

Claims

1. A method for controlling the activity ratio of terbium-160 to terbium-161 in the preparation of terbium-161, comprising: S1, targeting natural Gd or high abundance 160 Gd, 158 The Gd target was placed in the reactor for irradiation, then removed and cooled. The Gd target was then dissolved, and the dissolved solution was analyzed. 161 The radioactivity of Tb A Tb-161 and 159 The radioactivity of Gd, A Gd-159 Calculate the nuclear reaction rate Ø 热 σ Gd-160 and Ø 热 σ Gd-158 ; S2, the natural Tb target was placed in the reactor for irradiation, then removed and cooled to dissolve the natural Tb target. The dissolved solution was then analyzed. 160 The radioactivity of Tb A Tb-160 Calculate the nuclear reaction rate Ø 热 σ Tb-159 ; S3, based on the nuclear reaction rate data obtained from S1 and S2, calculates the high abundance 160 Gd target irradiation time and generation 160 Tb / 161 The relationship between Tb activity ratio.

2. The method according to claim 1, wherein, In S1, by calculating using Equations 1 and 2 respectively, we obtain... 160 Gd (n,γ) 161 Gd nuclear reaction rate Ø 热 σ Gd-160 (ns) -1 )and 158 Gd (n, γ) 159 Gd nuclear reaction rate Ø 热 σ Gd-158 (ns) -1 ): (Equation 1) (Equation 2) In Equations 1 and 2, Ø 热 The thermal neutron flux rate in the reactor, in n.cm -2 .s -1 ;σ Gd-160 nuclide 160 The thermal neutron reaction cross section of Gd, cm 2 ;σ Gd-158 nuclide 158 The thermal neutron reaction cross section of Gd, cm 2 N Gd-160 For irradiating Gd target 160 The number of Gd atoms; N Gd-158 For irradiating Gd target 158 The number of Gd atoms; λ Gd-159 nuclide 159 The decay constant of Gd, s -1 ;λ Tb-161 nuclide 161 The decay constant of Tb, s -1 ;λ Gd-161 nuclide 161 The decay constant of Gd, s -1 T is the Gd target irradiation time, in seconds; t is the time difference between the start and stop of the measurement, in seconds; A Tb-161 To generate products 161 The activity of Tb at the start of measurement, Bq; A Gd-159 To generate products 159 The activity of Gd at the start of the measurement, Bq.

3. The method according to claim 1 or 2, wherein, In S2, using Equation 3, we obtain... 159 Tb (n, γ) 160 Tb nuclear reaction rate Ø 热 σ Tb-159 (ns) -1 ): (Equation 3); In Equation 3, Ø 热 The flux of thermal neutrons in the reactor, n.cm -2 .s -1 ;σ Tb-159 nuclide 159 The thermal neutron reaction cross section of Tb, cm 2 N Tb-159 For irradiation of Tb target 159 The number of atoms of Tb; λ Tb-160 nuclide 160 The decay constant of Tb, s -1 T represents the Tb target irradiation time, in seconds; t represents the time difference between the start and end of the measurement, in seconds; A Tb-160 To generate products 160 The activity of Tb at the start of the measurement, Bq.

4. The method according to any one of claims 1 to 3, wherein, In S3, the relationship is obtained by calculation using Equation 4, where, 160 Gd (n, γ) 161 Gd, 158 Gd (n, γ) 159 The nuclear reaction rate of Gd was obtained from S1. 热 σ Gd-160 Ø 热 σ Gd-158 (ns) -1 ); 159 Tb (n, γ) 160 The Tb nuclear reaction rate was obtained from data in S2. 热 σ Tb-159 (ns) -1 ): (Equation 4) in, 。 5. The method according to any one of claims 1 to 4, wherein, The method further includes: Based on S3 160 Gd target irradiation time and generation 160 Tb / 161 The relationship between Tb activity ratio and irradiation time was optimized and controlled to achieve irradiation. 160 Gd target generation 160 Tb activity control.

6. The method according to any one of claims 1 to 5, wherein, The natural Gd target 158 Gd and 160 The abundance of Gd was 28.84% and 21.86%, respectively, which are high abundances. 160 Gd, 158 Gd target is 160 Gd abundance > 28.84%, 158 Targets with Gd abundance greater than 21.86%.

7. The method according to any one of claims 1 to 6, wherein, The natural Tb target has 100% 159 Tb.

8. The method according to any one of claims 1 to 7, wherein, The high-abundance Gd target has an abundance greater than 90%. 160 Gd.

9. The method according to any one of claims 1 to 8, wherein, Control the 160 Tb / 161 Tb activity ratio less than 1×10 -4 .

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