Method for producing < 225 > Ac nuclide < 227 > Ac with low proportion by high-current proton cyclotron

Abstract

The invention discloses a method for producing 225Ac nuclide with a low 227Ac proportion by a high-current proton cyclotron, which comprises the following steps: selecting an irradiation energy region of the 225Ac nuclide, the irradiation energy region being an irradiation energy region in which the capacity of the 225Ac nuclide and the low 227Ac / 225Ac proportion are comprehensively considered, the capacity being related to the thickness of a target material and being in direct proportion to the thickness of the target material, and the capacity being related to the thickness of the target material and being in direct proportion to the thickness of the target material; the thickness of the target material is greater than the thickness of the target material at the minimum 227Ac / 225Ac ratio; the number of irradiation days of the 225Ac nuclide is selected, the number of irradiation days is the number of irradiation days in which the capacity of the 225Ac nuclide and the 227Ac / 225Ac low proportion are comprehensively considered, and the capacity is not only related to the thickness of the target material, but also related to the number of irradiation days and is in direct proportion to the number of irradiation days; the number of cooling days of the 225Ac nuclide is selected, and the number of cooling days is the number of cooling days with the capacity of the 225Ac nuclide and the low ratio of 227Ac / 225Ac being comprehensively considered; aiming at the requirement of producing actinide 225 by using a thorium target through a medium-high energy cyclotron, the content of actinide 227 is reduced as much as possible while the sufficient batch yield of actinide 225 is ensured, so that the toxicity of corresponding drugs of 225Ac is reduced.

Description

Technical Field

[0001] The invention belongs to the technical field of cyclotron radioisotope production, and specifically provides a method for producing a low-ratio 227Ac nuclide of 225Ac by a high-current proton cyclotron. Background Art

[0002] 225Ac is the most popular alpha therapeutic nuclide in the market. It has a good therapeutic effect on prostate cancer, glioma, neurologic endocrine tumors, acute myeloid leukemia and other diseases. Due to the shortage of radium-226 and the limitations of its preparation methods, and the high fission cross-section, relatively abundant content and low price of thorium, the spallation reaction of protons and 232Th is currently the most promising method for preparing 225Ac.

[0003] One of the difficulties in preparing 225Ac is that the use of thorium targets to prepare 225Ac will produce the impurity nuclide 227Ac. The half-life of 227Ac is 21.77 years. This long-lived nuclide cannot be removed by natural decay, nor can it be separated from 225Ac by chemical separation methods. It will increase the toxicity of the corresponding drugs of 225Ac. Therefore, reducing the content of 227Ac while preparing 225Ac is an urgent problem that needs to be solved.

[0004] The second difficulty in preparing 225Ac nuclide is that the production capacity of 225Ac nuclide is proportional to the low proportion ratio of 227Ac / 225Ac. The smaller the low proportion ratio, the lower the production capacity of 225Ac nuclide. Therefore, while considering reducing the 227Ac content, we must also consider that the production capacity of 225Ac nuclide cannot be too low. The difficulty lies in finding a balance between the two. Summary of the invention

[0005] In order to solve the problems existing in the prior art, the present invention proposes a method for producing 225Ac nuclides with a low proportion of 227Ac by a high-current proton cyclotron. The first purpose is to reduce the content of 227Ac in the 225Ac nuclides; the second purpose is to solve the problem of comprehensively considering the production capacity of the 225Ac nuclides and the low proportion of 227Ac / 225Ac.

[0006] The present invention proposes the following technical solutions to solve the technical problems:

[0007] A method for producing 225Ac nuclide with low proportion of 227Ac by high-current proton cyclotron, characterized in that it comprises the following steps:

[0008] Step 1, selecting the irradiation energy zone of 225Ac nuclide, which is the irradiation energy zone that comprehensively considers the production capacity of 225Ac nuclide and the low ratio of 227Ac / 225Ac; the production capacity is related to the thickness of the target material and is proportional to the thickness of the target material, and the thickness of the target material is greater than the target material thickness when the lowest ratio of 227Ac / 225Ac is low;

[0009] Step 2, select the irradiation days of 225Ac nuclide, which is the irradiation days that comprehensively consider the production capacity of 225Ac nuclide and the low proportion of 227Ac / 225Ac; the production capacity is not only related to the target thickness but also related to the irradiation days, and is proportional to the irradiation days. The low proportion ratio of 227Ac / 225Ac after the irradiation days is greater than the low proportion ratio of 227Ac / 225Ac per unit time;

[0010] Step 3. Select the cooling days for 225Ac nuclide, which is a comprehensive consideration of the production capacity of 225Ac nuclide and the cooling days for the low proportion of 227Ac / 225Ac. The production capacity is not only related to the target thickness and the irradiation days, but also to the cooling days, and is inversely proportional to the cooling days. The low proportion value after the cooling days is the maximum low proportion value within the range of no more than 0.1%, and the production capacity is the production capacity corresponding to the maximum low proportion value within the range of no more than 0.1%.

[0011] Furthermore, the irradiation energy range of the step 1 comprehensively considering the production capacity of 225Ac nuclide and the low ratio of 227Ac / 225Ac includes 54MeV-69MeV, and the target thickness corresponding to its production capacity is 2.61mm, and the target density is 11.72g / cm3.

[0012] Furthermore, the step 2 comprehensively considers the production capacity of 225Ac nuclide and the irradiation days with low ratio of 227Ac / 225Ac, including 5 days (under the common current intensity of 200μA in isotope production, the current intensity and the yield are directly proportional). The production capacity after 5 days of irradiation is 353mCi, and the low ratio of 227Ac / 225Ac after 5 days of irradiation is 0.08%.

[0013] Furthermore, the step three comprehensively considers the production capacity of the 225Ac nuclide and the cooling days of the low proportion of 227Ac / 227Ac, ​​including 3 days. The maximum low proportion ratio within the range of no more than 0.1% after cooling for 3 days is 0.0986%, and the production capacity corresponding to the maximum low proportion ratio within the range of no more than 0.1% after cooling for 3 days is 287mCi.

[0014] Advantages and effects of the present invention

[0015] 1. The present invention aims at the demand of producing actinium-225 by using thorium target in medium and high energy cyclotron, and reduces the content of actinium-227 as much as possible while ensuring sufficient batch production of actinium-225, thereby reducing 225 Ac toxicity of corresponding drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 The reaction cross section for the production of 225Ac / 227Ac by accelerator bombardment of 232Th is recommended;

[0017] Figure 2 This is the curve of the yield ratio of 227Ac / 225Ac produced by proton bombardment of 232Th as a function of energy;

[0018] Figure 3 Curve showing the variation of 227Ac / 225Ac yield ratio with energy when different energies are deposited on the target

[0019] Figure 4 Table 1: 227Ac and 225Ac yields and ratios when protons bombarded thorium targets with different energies (200 μA, irradiation for 5 days);

[0020] Figure 5 Table 2: Yield and ratio of 227Ac and 225Ac in 5-day bombardment of thorium target by 54MeV-69MeV protons

[0021] Figure 6a The curve of 225Ac yield changing with time in the range of 5 days;

[0022] Figure 6b The curve of 225Ac yield changing with time in the range of 50 days;

[0023] Figure 7 The curve of 227Ac yield changing with time;

[0024] Figure 8 The figure is a flow chart of the method of the present invention. DETAILED DESCRIPTION

[0025] Design principle of the present invention

[0026] 1. Innovations of the present invention: The irradiation energy zone is the irradiation energy zone that comprehensively considers the production capacity of 225Ac nuclides and the low proportion of 227Ac / 225Ac; the irradiation days are the irradiation days that comprehensively consider the production capacity of 225Ac nuclides and the low proportion of 227Ac / 225Ac; the cooling days are the cooling days that comprehensively consider the production capacity of 225Ac nuclides and the low proportion of 227Ac / 225Ac;

[0027] 2. The design principle for selecting the irradiation energy range of 54-69MeV: ① The thickness of the target material is proportional to the production capacity. Figure 1-3 As shown, there are a total of 5 curves (the horizontal axis represents the energy injected into the target, and the vertical axis represents the ratio of 227Ac / 225Ac). Each curve represents a different target thickness. The thickness of the 225Ac nuclide target is proportional to the production capacity of the 225Ac nuclide. The thicker the target, the higher the production capacity; ② The energy deposited on the target is proportional to the thickness of the target. When the target thickness is thicker, the more energy the proton consumes to pass through the target. Since the energy consumed by the proton is deposited on the target, the amount of energy deposited on the target represents the thickness of the target. ③ Comprehensively consider the relationship between production capacity and low proportion. First, select the unit low proportion: the unit low proportion is the low proportion with the lowest ratio among the low proportions in different links of the nuclide production process. The reason why the unit low proportion ratio is the lowest is that with the progress of the irradiation and cooling links, the ratio of 227Ac / 225Ac will increase, so the unit low proportion should leave room for the final low proportion, so that the final low proportion ratio is less than 0.1%. The final low ratio is the low ratio after cooling for 3 days (from unit low ratio → irradiation for 5 days → cooling for 3 days). In order to make the final low ratio less than 0.1%, the reverse calculation method is used to calculate that the unit low ratio cannot be greater than 0.7%. Second, while meeting the design requirements of the unit low ratio, increase the output as much as possible. Figure 3 It can be seen that there are 4 curves whose low proportion value cannot be greater than 0.07%. From these 4 curves, the curve with high yield, that is, the curve with more energy deposited on the target, is selected as much as possible. Therefore, the curve with 15MeV deposited on the target is selected. The target thickness corresponding to this curve is 2.61mm. At the same time, the irradiation energy range is determined to be 54-69MeV: the energy of the proton when it enters the target is 69MeV, and the energy when it exits the target is 54MeV. The energy consumed on the target is 15MeV, which is the energy deposited on the target.

[0028] 3. Design principle of selecting 5 days of irradiation: The irradiation days are proportional to the production capacity, but it is necessary to select an appropriate irradiation day. If the irradiation days exceed this value, although the production capacity increases, the low-temperature ratio increases, resulting in the final low-temperature ratio (low-temperature ratio after 3 days of cooling) greater than 0.1%, which is undesirable in design. The appropriate irradiation days are selected as 5 days in this embodiment. The design principle is as follows: Figure 6a , Figure 6b , Figure 7As shown in the figure, when the irradiation days exceed 5 days, although the production capacity increases, the low proportion increases, resulting in the final low proportion (low proportion after cooling for 3 days) greater than 0.1%. The reason is that with the increase of irradiation days, 225Ac shows a trend of continuous attenuation, while the attenuation of 227Ac remains unchanged or does not decay. The reason is that the half-life of 227Ac is 21.77 years, while the half-life of 225Ac is 9.92 days. Although 225Ac shows a trend of continuous attenuation, the attenuation change rate in the first 5 days is very small and almost approximates a straight line. Therefore, a 5-day irradiation time is selected. After 5 days, the low proportion increases from 0.07% to 0.08%. The reason for the increase in the low proportion is that during the 5-day irradiation period, in the ratio of 227Ac / 225Ac, the production capacity value of 227Ac remains unchanged, and the attenuation of the production capacity of 225Ac is slow but still decays.

[0029] 4. The design principle of choosing a cooling period of 3 days: The cooling time will also affect 227 Ac / 225 The ratio of Ac, after 5 days of irradiation and continued cooling, the yield change rate of Ac225 and Ac227 is as follows Figure 6b , Figure 7 As shown in the figure, after 5 days of irradiation, the curve of Ac227 is a horizontal straight line, while the yield of Ac225 shows a downward trend. At this time, the ratio of 227Ac / 225Ac will be further increased. Therefore, the design of cooling days should be based on both meeting functional requirements and making 227 Ac / 225 The ratio of Ac should not exceed 0.1% as a guideline. Figure 5 As shown, when the cooling days are determined to be 3 days, the ratio of 227Ac / 225Ac after 3 days increases to 0.0986%. Although the low proportion increases from 0.08% before cooling to 0.0986%, it still does not exceed 0.1%. Therefore, determining the cooling days to be 3 days meets the requirements, and the corresponding output is 287mCi.

[0030] Based on the above invention principle, the present invention designs a method for producing 225Ac nuclides with low proportion of 227Ac by high current proton cyclotron. Figure 8 As shown, its characteristic is that it includes the following steps:

[0031] Step 1, selecting the irradiation energy zone of 225Ac nuclide, which is the irradiation energy zone that comprehensively considers the production capacity of 225Ac nuclide and the low ratio of 227Ac / 225Ac; the production capacity is related to the thickness of the target material and is proportional to the thickness of the target material, and the thickness of the target material is greater than the target material thickness when the lowest ratio of 227Ac / 225Ac is low;

[0032] Step 2, select the irradiation days of 225Ac nuclide, which is the irradiation days that comprehensively consider the production capacity of 225Ac nuclide and the low proportion of 227Ac / 225Ac; the production capacity is not only related to the target thickness but also related to the irradiation days, and is proportional to the irradiation days. The low proportion ratio of 227Ac / 225Ac after the irradiation days is greater than the low proportion ratio of 227Ac / 225Ac per unit time;

[0033] Supplementary Note 1:

[0034] Under the 200μA current intensity common in isotope production, the current intensity and yield are directly proportional.

[0035] Step 3. Select the cooling days for 225Ac nuclide, which is a comprehensive consideration of the production capacity of 225Ac nuclide and the cooling days for the low proportion of 227Ac / 225Ac. The production capacity is not only related to the target thickness and the irradiation days, but also to the cooling days, and is inversely proportional to the cooling days. The low proportion value after the cooling days is the maximum low proportion value within the range of no more than 0.1%, and the production capacity is the production capacity corresponding to the maximum low proportion value within the range of no more than 0.1%.

[0036] Furthermore, the irradiation energy range of the step 1 comprehensively considering the production capacity of 225Ac nuclide and the low ratio of 227Ac / 225Ac includes 54MeV-69MeV, and the target thickness corresponding to its production capacity is 2.61mm, and the target density is 11.72g / cm3.

[0037] Furthermore, the step 2 comprehensively considers the production capacity of 225Ac nuclide and the irradiation days with low ratio of 227Ac / 225Ac, including 5 days (under the common current intensity of 200μA in isotope production, the current intensity and the yield are directly proportional). The production capacity after 5 days of irradiation is 353mCi, and the low ratio of 227Ac / 225Ac after 5 days of irradiation is 0.08%.

[0038] Furthermore, the step three comprehensively considers the production capacity of the 225Ac nuclide and the cooling days of the low proportion of 227Ac / 227Ac, ​​including 3 days. The maximum low proportion ratio within the range of no more than 0.1% after cooling for 3 days is 0.0986%, and the production capacity corresponding to the maximum low proportion ratio within the range of no more than 0.1% after cooling for 3 days is 287mCi.

[0039] Embodiment 1

[0040] Step 1: Select the peak area for producing 225Ac. Figure 1As shown in the figure, in order to ensure that the batch production of actinium-225 is sufficient while reducing the content of actinium-227 as much as possible, the energy selection and irradiation time selection of the thorium target irradiated by the accelerator are very critical issues. The International Atomic Energy Agency (IAEA) combined with the experimental data of foreign laboratories gave the reaction cross section of bombarding 232Th to produce 225Ac / 227Ac. The reaction threshold of 232Th(p,x)225Ac is about 40MeV, the reaction threshold of 232Th(p,x)227Ac is about 20MeV, and the peak value of the low-energy region of 227Ac is about 44MeV. The energy region of 70MeV→50MeV is a peak region for the production of 225Ac.

[0041] Step 2: Consider the target's production capacity and low proportion and then select the irradiation area.

[0042] 54MeV-69MeV

[0043] ⑴ Preliminary selection of 70MeV→50MeV energy range. Figure 2 As shown in the figure, according to the data recommended by IAEA, the curves of 227Ac / 225Ac ratios at different energies under thin targets are obtained. Although the reaction cross section of 227Ac gradually decreases from 160MeV, the 227Ac / 225Ac ratio is lower than 0.1% at 180MeV. The lowest 227Ac / 225Ac ratio in the 180MeV-200MeV energy range is 0.088%. Considering the time required for the decay of 225Ac itself and the separation and purification, it is impossible to achieve the index of 227Ac<0.1% in this energy range. The 70MeV→50MeV energy range is a peak area for the production of 225Ac, and is also a valley area for the production of 227Ac. The lowest 227Ac / 225Ac ratio is 0.060%, which is the best irradiation range for the production of 225Ac.

[0044] ⑵ Consider the thickness of the target and select the irradiation energy range of 54MeV-69MeV. Figure 3 As shown, considering the low yield of thin targets, the 227Ac / 225Ac ratio curves at different energy deposited in the target are compared. As the energy deposited on the target increases and the target thickness increases, the lowest ratio range of 227Ac / 225Ac shifts toward the high energy zone, and the ratio increases. Therefore, considering both the yield of 225Ac and the 227Ac / 225Ac ratio, the irradiation energy zone of 54MeV-69MeV is selected. At this time, the corresponding curve is the curve with an energy of 15MeV deposited on the target. The 227Ac / 225Ac ratio at the lowest point of the curve is 0.069%. At this time, the 54MeV-69MeV energy zone requires a thorium target thickness of 2.61mm and a target density of 11.72g / cm 3 .

[0045] Step 3: After comprehensively considering the production capacity and low proportion, the irradiation days are determined to be 5 days

[0046] Irradiation time will affect 227 Ac / 225 The ratio of Ac, if the irradiation time is too short, 225 The yield of Ac is insufficient. If the irradiation time is too long, it will lead to 227 Ac / 225 The ratio of Ac increases significantly. Consider 225 The half-life of Ac is 9.92 days. 225 Ac is decaying at the same time, such as Figure 7 As shown, within the range of 120 hours (5 days) on the horizontal axis, 227 The long half-life of Ac can be considered that it basically does not decay, because the horizontal axis ranges from 0 to 120 227 The slope of Ac is always a straight line, and within the same range, Figure 6a of 225 The horizontal coordinate of Ac ranges from 0 to 120, which is approximately an arc. Due to the short time of only 5 days, the decay is not obvious. Figure 6b As shown, in the larger time frame of 50 days 225 The degree of attenuation of Ac is very obvious as the number of irradiation days increases. Therefore, the present invention intercepts 120 hours from 0 to 5 days. 225 The number of days of irradiation during which the Ac attenuation is not very obvious is 5 days. Figure 4 Table 1 shows that when the energy range is 54-69 MeV, the yield after 5 days of irradiation is 353 mCi, and the 227Ac / 225Ac low ratio is 0.08%. Compared with before irradiation, the 227Ac / 225Ac low ratio increased from 0.069% to 0.08%, which is still less than 0.1%.

[0047] Step 4: After comprehensively considering the production capacity and low proportion, the cooling days are determined to be 3 days.

[0048] Cooling time also affects 227 Ac / 225 The ratio of Ac. If the cooling time is too short, the task cannot be completed during this period. If the cooling time is too long, it will lead to 227 Ac / 225 To ensure that both the irradiation yield and the ratio meet the requirements, a simulation was performed and the proton beam current was 200μA for 5 days and then cooled for 3 days. The cross section, yield and other data recommended by the IAEA official website were used to calculate the yield of proton bombardment of the thorium target under the current irradiation conditions. 227 Ac, 225 The yield and rate of Ac nuclides are shown in Table 1.

[0049] Depend on Figure 5 Table 2 shows that the yield of 225Ac at the end of irradiation is 353mCi, the yield of 227Ac EOB is 0.283mCi, and the ratio of 227Ac / 225Ac is 0.080%. The cooling + separation time is less than 3 days, at which time the yield of 225Ac is 287mCi, and the ratio of 227Ac / 225Ac is 0.0986%<0.1%. Compared with before cooling, the ratio of 227Ac / 225Ac low ratio increased from 0.08% to 0.0986%, which is still less than 0.1%.

[0050] In summary, although both irradiation and cooling will lead to an increase in the low proportion ratio of 227Ac / 225Ac, due to the selection of appropriate irradiation days and appropriate cooling days, the low proportion ratio of 227Ac / 225Ac is less than 0.1%, while the low proportion ratio of 227Ac / 225Ac in the prior art is between 0.1% and 0.3%, which cannot reach the low proportion ratio of 227Ac / 225Ac of less than 0.1% in this embodiment.

[0051] It should be emphasized that the above specific embodiments are merely explanations of the present invention, and they are not limitations of the present invention. After reading this specification, those skilled in the art can make modifications to the above embodiments without any creative contribution as needed, but as long as they are within the scope of the claims of the present invention, they are protected by patent law.

Claims

1. A method for producing 225Ac nuclides with low proportion of 227Ac by high-current proton cyclotron. It is characterized in that The following steps are involved: Step 1, selecting the irradiation energy zone of 225Ac nuclide, which is the irradiation energy zone that comprehensively considers the production capacity of 225Ac nuclide and the low ratio of 227Ac / 225Ac; the production capacity is related to the thickness of the target material and is proportional to the thickness of the target material, and the thickness of the target material is greater than the target material thickness when the lowest ratio of 227Ac / 225Ac is low; Step 2, select the irradiation days of 225Ac nuclide, which is the irradiation days that comprehensively consider the production capacity of 225Ac nuclide and the low proportion of 227Ac / 225Ac; the production capacity is not only related to the target thickness but also related to the irradiation days, and is proportional to the irradiation days. The low proportion ratio of 227Ac / 225Ac after the irradiation days is greater than the low proportion ratio of 227Ac / 225Ac per unit time; Step 3. Select the cooling days for 225Ac nuclide, which is a comprehensive consideration of the production capacity of 225Ac nuclide and the cooling days for the low proportion of 227Ac / 225Ac. The production capacity is not only related to the target thickness and the irradiation days, but also to the cooling days, and is inversely proportional to the cooling days. The low proportion value after the cooling days is the maximum low proportion value within the range of no more than 0.1%, and the production capacity is the production capacity corresponding to the maximum low proportion value within the range of no more than 0.1%.

2. A method for producing 225Ac nuclides with low 227Ac content by a high-current proton cyclotron according to claim 1, It is characterized in that The step 1 comprehensively considers the production capacity of 225Ac nuclide and the irradiation energy range with a low ratio of 227Ac / 225Ac, including 54MeV-69MeV, and the target thickness corresponding to its production capacity is 2.61mm and the target density is 11.72g / cm3.

3. A method for producing a low proportion of 227Ac nuclides using a high-current proton cyclotron according to claim 1, It is characterized in that The step 2 comprehensively considers the production capacity of 225Ac nuclide and the irradiation days with low ratio of 227Ac / 225Ac, including 5 days (under the common 200μA current intensity condition of isotope production, the current intensity and the yield are directly proportional). The production capacity after 5 days of irradiation is 353mCi, and the low ratio of 227Ac / 225Ac after 5 days of irradiation is 0.08%.

4. According to claim 1, a method for producing 225Ac nuclides with low proportion of 227Ac by using a high-current proton cyclotron, It is characterized in that The step three comprehensively considers the production capacity of the 225Ac nuclide and the cooling days of the low proportion of 227Ac / 227Ac, ​​which includes 3 days. The maximum low proportion ratio within the range of no more than 0.1% after cooling for 3 days is 0.0986%. The production capacity corresponding to the maximum low proportion ratio within the range of no more than 0.1% after cooling for 3 days is 287mCi.

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