Cyclotron metal composite target for preparing targeted radionuclide drugs

Abstract

The present invention discloses a cyclotron metal composite target for preparing targeted radionuclide drugs, which comprises an aluminum substrate whose shape matches the shape of the target position of the accelerator. A bismuth layer is attached to or embedded in the surface of the aluminum substrate, and the thickness of the bismuth layer is 10-20 μm. The present invention provides a cyclotron metal composite target for preparing targeted radionuclide drugs, which can reduce or even avoid the melting of the target, improve the heat conduction efficiency of the target, and avoid the pollution of the equipment and its products.

Description

Technical Field

[0001] The present invention belongs to the field of preparation of targeted drugs, and relates to a cyclotron target, in particular to a cyclotron metal composite target. Background Art

[0002] In recent years, targeted radionuclide drugs containing radionuclides have made significant developments in the diagnosis and treatment applications of diseases, and have gradually become one of the mainstream drug means for cancer diagnosis and treatment. Targeted radionuclide drugs can deliver radionuclides to lesions (including cancer cells, etc.) through targeting molecules. Diagnostic radionuclides can release gamma rays with very strong penetrability to provide lesion information, while therapeutic radionuclides can accurately release a radiation dose sufficient to kill cancer tissues so as to achieve a therapeutic effect. Among numerous radionuclides, the alpha radionuclide astatine-211 ( 211 At) has good physical properties and is very suitable for therapeutic radionuclide drugs for treating cancer.

[0003] The most critical factor restricting the development and popularization of radionuclide drugs is the production source of radionuclide drugs. At present, only the Institute of Nuclear Science and Technology of Sichuan University in China has reported limited production, research and application of astatine-211, and there is no report on cases of large-scale production of astatine-211 sufficient for clinical use.

[0004] The mainstream method for producing astatine-211 uses a high-energy alpha particle beam generated by a cyclotron to bombard a metal bismuth target, and produces astatine-211 through the 209 Bi(α, 2n) 211 At nuclear reaction. However, due to the low melting point of metal bismuth, only 272 °C, and poor thermal conductivity, only 7.97 W / (K×m). Therefore, in the case of bombardment by a high-energy particle beam, the phenomenon of target melting is likely to occur, resulting in a reduction in production efficiency or contamination and damage of production equipment. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to provide a cyclotron metal composite target for preparing targeted radionuclide drugs, which can reduce or even avoid target melting, improve the thermal conductivity efficiency of the target, and avoid contamination of equipment and its products, aiming at the defects of the prior art.

[0006] The technical solution adopted by the present invention to solve its technical problems is: a cyclotron metal composite target for preparing targeted radionuclide drugs, including an aluminum substrate whose shape matches the shape of the target position of the accelerator, and a bismuth layer is attached to or embedded in the surface of the aluminum substrate, and the thickness of the bismuth layer is 10-20 μm.

[0007] Further, in the cyclotron metal composite target material for preparing the targeted radionuclide drug, preferably, the aluminum substrate includes an edge portion disposed on both sides and a central portion disposed between the edge portions, and the top surface of the edge portion is higher than the top surface of the central portion; the bismuth layer is disposed on the central portion.

[0008] Further, in the cyclotron metal composite target material for preparing the targeted radionuclide drug, preferably, the central portion is axially provided with a concave base groove, the bismuth layer is filled and embedded in the base groove, and the bismuth layer is flush with the surface of the central portion.

[0009] Further, in the cyclotron metal composite target material for preparing the targeted radionuclide drug, preferably, the base groove is a through groove penetrating through both ends of the central portion of the aluminum substrate; or the base groove is an end-sealed groove with both ends closed, and the central portions on both axial sides of the end-sealed groove are heat absorption regions.

[0010] Further, in the cyclotron metal composite target material for preparing the targeted radionuclide drug, preferably, the bismuth layer is in a dense non-porous state.

[0011] Further, in the cyclotron metal composite target material for preparing the targeted radionuclide drug, preferably, the width of the bismuth layer is 1 cm and the length is 7.5 - 8.5 cm.

[0012] Further, in the cyclotron metal composite target material for preparing the targeted radionuclide drug, preferably, the bottom surface of the base groove is an arc surface, the arc surface is axially symmetric about the aluminum substrate, and its lowest point is on the central axis of the aluminum substrate; or the lowest point of the bottom surface of the base groove is located at the center of the aluminum substrate, and its periphery smoothly transitions from the top surface of the central portion to the lowest point of the base groove.

[0013] Further, in the cyclotron metal composite target material for preparing the targeted radionuclide drug, preferably, the back surface of the aluminum substrate is provided with a concave cooling groove.

[0014] Further, in the cyclotron metal composite target material for preparing the targeted radionuclide drug, preferably, a plurality of the cooling grooves are arranged at intervals, and the shape of the cooling groove is a polygon, a curved surface or a combination thereof.

[0015] The target material of the present invention is a composite target material of an aluminum substrate with a bismuth layer. The aluminum substrate itself has good thermal conductivity, and the melting point of aluminum metal is 660.4 °C, which reduces the temperature of the bismuth layer and thus reduces the possibility of the target material melting, and increases the limit of the maximum beam current intensity. At the same time, by reducing the thickness of the bismuth target material to 10 to 20 μm, the utilization rate of the bismuth target material is increased and the temperature rise of the target material is reduced, the melting of the bismuth target material is reduced, and the limit of the maximum beam current intensity is increased; furthermore, reducing the thickness of the target material can accelerate the release of astatine-211 during the distillation process and reduce the requirement for the distillation temperature, increasing the average production yield of astatine-211 from 10.6 ± 1.2 megabecquerels per microampere-hour to 41 ± 7 megabecquerels per microampere-hour, and increasing the maximum production capacity to nine billion becquerels. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The present invention will be further described below in conjunction with the drawings and embodiments. In the drawings:

[0017] Figure 1 is a perspective view of the first embodiment of the present invention;

[0018] Figure 2 is a front structural schematic diagram of the aluminum substrate of the first embodiment of the present invention;

[0019] Figure 3 is a back structural schematic diagram of the aluminum substrate of the first embodiment of the present invention;

[0020] Figure 4 is a perspective view of the second embodiment of the present invention;

[0021] Figure 5 is a front structural schematic diagram of the aluminum substrate of the second embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0022] In order to have a clearer understanding of the technical features, objectives, and effects of the present invention, the specific embodiments of the present invention will now be described in detail with reference to the drawings.

[0023] A component is referred to as "fixed to" or "disposed on" another component, and it can be directly or indirectly located on that another component. When a component is referred to as "connected to" another component, it can be directly or indirectly connected to that another component.

[0024] The terms "upper", "lower", "left", "right", "front", "rear", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc. indicate the orientation or position based on the orientation or position shown in the drawings.

[0025] The terms "axial", "radial", and "transverse" refer to the "axial direction" along the length of the entire device or component, and the directions perpendicular to the axial direction are the "radial direction" or "transverse direction".

[0026] The terms "first", "second", etc. are only used for the purpose of convenient description and should not be construed as indicating or implying relative importance or implicitly specifying the quantity of technical features. The meaning of "a plurality" is two or more, unless otherwise clearly and specifically defined.

[0027] The above terms are only for convenient description and should not be construed as limitations to the technical solution of the present invention.

[0028] The metal composite target of the present invention is used in a cyclotron for preparing targeted radionuclide drugs. According to different cyclotrons, the target size requirements are different, but the structural requirements are the same.

[0029] The following takes the CS-30 model cyclotron as an example for detailed description:

[0030] As Figures 1-5 shown, a cyclotron metal composite target for preparing targeted radionuclide drugs includes an aluminum substrate 100 whose shape matches the shape of the target position of the accelerator. A bismuth layer 200 is attached or embedded on the surface of the aluminum substrate 100, and the thickness of the bismuth layer 200 is 10 - 20 μm. The thickness range of the bismuth layer 200 is based on the prior art, reducing the thickness of the metallic bismuth layer 200 to 10 to 20 μm, which increases the utilization rate of the metal bismuth target, that is, improves the production of At-211 per unit volume or unit mass. And due to the thinning of the bismuth layer 200, the heat conduction of the aluminum substrate 100 is increased, reducing the temperature rise of the target, reducing or even avoiding the melting of the bismuth target, and improving the limit of the maximum beam current intensity; at the same time, reducing the thickness of the target can accelerate the release of astatine-211 during the distillation process and reduce the requirement for the distillation temperature.

[0031] When the cyclotron is operating, the energy of the incident high-energy alpha particle beam is 29 MeV. As the particle beam interacts with the target, the energy of the particle beam decreases. When incident at an angle of 4.7 degrees, at a thickness below 10 μm of the target, the energy of the alpha particle beam drops below 20 MeV, and this particle beam energy is already below the energy range for generating astatine-211, so astatine-211 is no longer generated. Therefore, the present invention uses a target with a thickness not less than 10 μm. Determined by the heat generation of the bismuth target, the thicker the target, the easier it is to melt and cause production failure. The maximum thickness of the target of the present invention is selected as 20 μm. Therefore, the thickness of the bismuth layer 200 of the present invention is between 10 and 20 μm.

[0032] The composite target of the present invention comprises two parts, an aluminum substrate 100 and a bismuth layer 200. The appearance shape of the aluminum substrate 100 is consistent with the shape of the built-in target position of the cyclotron. The overall shape of the aluminum substrate 100 of the present invention is a strip-shaped axially concave structure, which is an integrally formed one-piece structure. Its size is preferably 9.5 cm in length, 2.1 cm in width, and 0.6 cm in thickness. Specifically, its main structure is that the aluminum substrate 100 includes edge portions 110 arranged on both sides and a central portion 120 arranged between the edge portions 110. The top surfaces of the two side edge portions 110 are flush and are both flat surfaces. The top surface of the edge portion 110 is higher than the top surface of the central portion 120. This shape structure is also consistent with the shape of the built-in target position of the cyclotron. The width of the central portion 120 is preferably 1 cm, and the bismuth layer 200 is arranged on the central portion 120.

[0033] An axially concave base groove is provided in the central portion 120. The bismuth layer 200 is filled and embedded in the base groove. The bismuth layer 200 can attach the metal bismuth material to the base groove of the central portion 120 by means of magnetron sputtering. The wall surface of the base groove can be a smooth plane or a rough surface, which does not affect the attachment of the bismuth material. The cross-sectional shape of the base groove is not limited and can be any structure from the groove opening width to the edge portion 110. For example, it can be a square, trapezoidal, U-shaped, arc-shaped, other curve or straight line combination and other structures. It is preferably a symmetric structure. More preferably, the cross-sectional shape of the base groove is U-shaped, that is, the two side wall surfaces are perpendicular to the bottom surface or the top surface of the aluminum substrate 100. It is further preferably that the cross-section of the base groove is arc-shaped, the bottom surface of the base groove is an arc surface, and the arc surface is axially symmetric about the aluminum substrate 100, and its lowest point is on the central axis of the aluminum substrate 100. Or it can be that the lowest point of the bottom surface of the base groove is located at the center of the aluminum substrate 100, and its periphery smoothly transitions from the top surface of the central portion 120 to the lowest point of the base groove. The base groove is symmetric about the axial center line and the transverse center line of the aluminum substrate 100.

[0034] The depth of the base groove is 10 - 20 μm, which can refer to the average depth of the base groove or the lowest point depth is 10 - 20 μm. Preferably, the maximum lowest point depth is 20 μm. Specifically, the depth of the base groove can be selected as any value within this range. Preferably, the depths are 10, 12, 15, 17, 18, 20 μm. The bismuth layer 200 is flush with the surface of the central portion 120, and the thickness of the bismuth layer 200 can also be arbitrarily selected between 10 - 20 μm. Preferably, the thicknesses are 10, 12, 15, 17, 18, 20 μm.

[0035] The base groove is divided into two implementation manners according to its structure:

[0036] Such as Figures 1-3As shown, the first embodiment is as follows: The base groove is an end-sealed groove with both ends closed, and the central parts 120 on both axial sides of the end-sealed groove are heat absorption areas 300. In this embodiment, the base groove is only located in the middle, relatively reducing the axial length of the base groove. Both ends of the base groove are aluminum substrates 100. Since both ends of the aluminum substrate 100 are high-temperature regions, bismuth materials are not provided here to avoid melting of the bismuth materials here. At the same time, the overall temperature of the bismuth layer 200 is also reduced, which can increase the limit of the maximum beam current intensity, and thus increase the production yield of astatine-211.

[0037] According to the temperature distribution, high-temperature regions exist at both ends of the target. Preferably, the width of the bismuth layer 200 is 1 cm and the length is 7.5 - 8.5 cm. Within this size range, on the one hand, it meets the requirements of the cyclotron for the target. At the same time, aluminum metal with a higher melting point and better thermal conductivity is set in the high-temperature region, avoiding melting of the target and providing optimal conditions for the production of astatine-211. The length of the bismuth layer 200 can be any data within the above range.

[0038] As Figures 4-5 shown, the second embodiment is as follows: The base groove is a through groove that penetrates to both ends of the central part 120 of the aluminum substrate 100, that is, the length of the base groove is the same as the length of the aluminum substrate 100; the bismuth layer 200 is filled in the base groove and extends from one end of the aluminum substrate 100 to the other end. In this structural method, the thickness of the bismuth layer 200 is reduced, the utilization rate of the bismuth layer 200 is increased, and heat is conducted through the aluminum substrate 100. Through the overall thermal conductivity of the target, the overall temperature of the target is reduced, avoiding pollution problems caused by melting of the target.

[0039] The bismuth layer 200 is formed by attaching metallic bismuth material to the aluminum substrate 100 through a magnetron sputtering method. This method can be carried out by using the existing magnetron sputtering method and will not be elaborated here. The bismuth layer 200 is completely attached in the base groove of the aluminum substrate 100, and its structure is a dense non-porous state. This state means that the density of bismuth metal in the sputtered bismuth layer 200 reaches 9.8 g / cm 3 of a dense structure without abnormal air holes.

[0040] As Figure 3 shown, in order to further reduce the temperature of the target, a concave cooling groove 500 is provided on the back of the aluminum substrate 100. A plurality of the cooling grooves 500 are arranged at intervals, and the shape of the cooling groove 500 is a polygon, a curved surface, or a combination thereof. The cooling groove 500 is used for water cooling to reduce the temperature by increasing the heat dissipation area of the aluminum substrate 100.

[0041] The following is a detailed description through specific examples:

[0042] Example 1. A cyclotron metal composite target for preparing targeted radionuclide drugs, comprising an aluminum substrate 100 whose shape matches the shape of the target position of the accelerator. A bismuth layer 200 is attached to or embedded in the surface of the aluminum substrate 100. The aluminum substrate 100 has a size of 9.5 cm in length, 2.1 cm in width, and 0.6 cm in thickness. The base groove penetrates through both ends of the aluminum substrate 100 and has a size of 9.5 cm in length and 1 cm in width. Specifically, the cross-section of the base groove is a downward concave arc with a radius of 71 cm, and the deepest point is at the center (axial center line) of the aluminum substrate 100, with a depth of 0.2 cm. The bismuth layer 200 has a thickness of 20 μm, a length of 9.5 cm, and a width of 1 cm. There are 7 cooling grooves 500 with a depth of 0.2 cm, a width of 0.2 cm, and a length of 7 cm on the back of the aluminum substrate 100 for cooling with cooling water. The cross-section of the cooling groove 500 is square.

[0043] Example 2. A cyclotron metal composite target for preparing targeted radionuclide drugs, comprising an aluminum substrate 100 whose shape matches the shape of the target position of the accelerator. A bismuth layer 200 is attached to or embedded in the surface of the aluminum substrate 100. The aluminum substrate 100 has a size of 9.5 cm in length, 2.1 cm in width, and 0.6 cm in thickness. The base groove is a sealed-end groove with a size of 8 cm in length and 1 cm in width. The lengths of the heat absorption areas 300 at both ends are 0.75 cm respectively. The cross-section of the base groove is square. The bismuth layer 200 has a thickness of 10 μm, a length of 8 cm, and a width of 1 cm. There are 5 cooling grooves 500 with a depth of 0.3 cm, a width of 0.15 cm, and a length of 8 cm on the back of the aluminum substrate 100 for cooling with cooling water. The cross-section of the cooling groove 500 is arc-shaped.

[0044] Example 3. A cyclotron metal composite target for preparing targeted radionuclide drugs, comprising an aluminum substrate 100 whose shape matches the shape of the target position of the accelerator. A bismuth layer 200 is attached to or embedded in the surface of the aluminum substrate 100. The aluminum substrate 100 has a size of 9.5 cm in length, 2.1 cm in width, and 0.6 cm in thickness. The base groove is a sealed-end groove with a size of 7.5 cm in length and 1 cm in width. Specifically, the lowest point of the bottom surface of the base groove is located at the center of the aluminum substrate 100, and its periphery smoothly transitions from the top surface of the central part 120 to the lowest point of the base groove. The base groove is symmetric about the axial center line and the transverse center line of the aluminum substrate 100. The depth of the lowest point groove is 20 μm. The bismuth layer 200 has a thickness of 10 μm - 20 μm, a length of 7.5 cm, and a width of 1 cm. There are 4 cooling grooves 500 with a depth of 0.2 cm, a width of 0.3 cm, and a length of 7 cm on the back of the aluminum substrate 100 for cooling with cooling water. The cross-section of the cooling groove 500 is U-shaped.

[0045] Example 4. A cyclotron metal composite target for preparing targeted radionuclide drugs, comprising an aluminum substrate 100 whose shape matches the shape of the target position of the accelerator. A bismuth layer 200 is attached to or embedded in the surface of the aluminum substrate 100. The aluminum substrate 100 has a size of 9.5 cm in length, 2.1 cm in width, and 0.6 cm in thickness. The base groove is a sealed-end groove with a size of 8.2 cm in length and 1 cm in width. Specifically, the cross-section of the base groove is square, the bismuth layer 200 has a thickness of 15 μm, a length of 8.2 cm, and a width of 1 cm. There are 6 cooling grooves 500 with a depth of 0.2 cm, a width of 0.2 cm, and a length of 8 cm on the back of the aluminum substrate 100 for cooling with cooling water. The cross-section of the cooling groove 500 is V-shaped.

[0046] Experimental test: The target materials of Examples 1-3 of the present invention were respectively used to prepare astatine-211, and the preparation process and the astatine-211 product were detected. The parameters of the cyclotron were: a heating power of 1500 W

[0047] The following results were obtained:

[0048]

[0049] It can be seen from the above table that the highest temperature of the target material of the present invention is 189.3 °C, which is lower than the melting temperature of metallic bismuth. Under the condition of the same power, the highest temperature of the target material in the prior art is 284.3 °C. Therefore, the target material of the present invention effectively avoids the problem of the target material melting and contaminating the product. Through the half-life test, the half-life of astatine-211 produced by the target material of the present invention is consistent with the literature report. For the purity detection of the product astatine-211, the impurity content is below 2.3 ppm, which is greatly reduced compared with the prior art. The production yield of astatine-211 is increased to more than 41 megabecquerels per microampere-hour.

Claims

1. A cyclotron metal composite target for preparing targeted radionuclide drugs, characterized in that, The radionuclide is astatine-211; it includes an aluminum substrate whose shape matches the shape of the target position of the accelerator, and a bismuth layer is attached to or embedded in the surface of the aluminum substrate, and the thickness of the bismuth layer is 10-20 μm; The aluminum substrate includes edge portions arranged on both sides and a central portion arranged between the edge portions; The central portion is provided with a concave base groove along the axial direction, the bismuth layer is filled and embedded in the base groove, and the bismuth layer is flush with the surface of the central portion; The base groove is a through groove that penetrates to both ends of the central portion of the aluminum substrate; or the base groove is an end-sealed groove with both ends closed, and the central portions on both axial sides of the end-sealed groove are heat absorption areas.

2. The cyclotron metal composite target for preparing the targeted radionuclide drug according to claim 1, wherein The top surface of the edge portion is higher than the top surface of the central portion; the bismuth layer is arranged on the central portion.

3. The cyclotron metal composite target for preparing the targeted radionuclide drug according to claim 1, wherein The bismuth layer is in a dense non-porous state.

4. The cyclotron metal composite target for preparing the targeted radionuclide drug according to claim 1, wherein, The width of the bismuth layer is 1 cm, and the length is 7.5-8.5 cm.

5. The cyclotron metal composite target for preparing the targeted radionuclide drug according to claim 1, wherein, The bottom surface of the base groove is an arc surface, which is axially symmetric about the aluminum substrate, and its lowest point is on the central axis of the aluminum substrate; or the lowest point of the bottom surface of the base groove is located at the center of the aluminum substrate, and its periphery smoothly transitions from the top surface of the central portion to the lowest point of the base groove.

6. The cyclotron metal composite target material for preparing the targeted radionuclide drug according to claim 1, wherein, A concave cooling groove is provided on the back surface of the aluminum substrate.

7. The cyclotron metal composite target material for preparing the targeted radionuclide drug according to claim 6, wherein A plurality of the cooling grooves are arranged at intervals, and the shape of the cooling groove is a polygon, a curved surface, or a combination thereof.

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